bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection
Authors: Anuradha Rajamanickam , Munisankar Saravanan , Bhootra Yukthi , Dolla Chandrakumar , Kumaran Paul , Nutman Thomas B. , Babu Subash 
Published: February 2017

ABSTRACT

Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent
Strongyloides stercoralis
infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent
S. stercoralis
infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-β]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-β) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in
S. stercoralis
-LTB coinfection is reversible (for the most part) by anthelmintic treatment.
Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets
Authors: Elahi Shokrollah , Thompson David R. , Van Kessel Jill , Babiuk Lorne A. , Gerdts Volker 
Published: February 2017

ABSTRACTMaternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g., tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-6 [IL-6], IL-8, and IL-12/IL-23p40) in addition to pertussis-specific antibodies. These cytokines can be detected in the sera and colostrum/milk of vaccinated sows and subsequently were detected at significant levels in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows together with pertussis-specific antibodies. In contrast, active vaccination of newborn piglets with heat-inactivated bacteria induced high levels of specific IgG and IgA but no cytokines. Although the levels of antibodies in vaccinated piglets were comparable to those of passively transferred antibodies, no protection againstBordetella pertussisinfection was observed. Thus, our results demonstrate that a combination of passively transferred cytokines and antibodies is crucial for disease protection. The presence of passively transferred cytokines/antibodies influences the cytokine secretion ability of splenocytes in the neonate, which provides novel evidence that maternal immunization can influence the newborn's cytokine milieu and may impact immune cell differentiation (e.g., Th1/Th2 phenotype). Therefore, these maternally derived cytokines may play an essential role both as mediators of early defense against infections and possibly as modulators of the immune repertoire of the offspring.
DdaR (PA1196) Regulates Expression of Dimethylarginine Dimethylaminohydrolase for the Metabolism of Methylarginines in Pseudomonas aeruginosa PAO1
Authors: Lundgren Benjamin R. , Bailey Frank J. , Moley Gabriella , Nomura Christopher T. 
Published: February 2017

ABSTRACT

Dimethylarginine dimethylaminohydrolases (DDAHs) catalyze the hydrolysis of methylarginines to yield
l
-citrulline and methylamines as products. DDAHs and their central roles in methylarginine metabolism have been characterized for eukaryotic cells. While DDAHs are known to exist in some bacteria, including
Streptomyces coelicolor
and
Pseudomonas aeruginosa
, the physiological importance and genetic regulation of bacterial DDAHs remain poorly understood. To provide some insight into bacterial methylarginine metabolism, this study focused on identifying the key elements or factors regulating DDAH expression in
P. aeruginosa
PAO1. First, results revealed that
P. aeruginosa
can utilize
N

G

,
N

G

-dimethyl-
l
-arginine (ADMA) as a sole source of nitrogen but not carbon. Second, expression of the
ddaH
gene was observed to be induced in the presence of methylarginines, including
N

G

-monomethyl-
l
-arginine (
l
-NMMA) and ADMA. Third, induction of the
ddaH
gene was shown to be achieved through a mechanism consisting of the putative enhancer-binding protein PA1196 and the alternative sigma factor RpoN. Both PA1196 and RpoN were essential for the expression of the
ddaH
gene in response to methylarginines. On the basis of the results of this study, PA1196 was given the name DdaR, for
d
imethylarginine
d
imethyl
a
minohydrolase
r
egulator. Interestingly, DdaR and its target
ddaH
gene are conserved only among
P. aeruginosa
strains, suggesting that this particular
Pseudomonas
species has evolved to utilize methylarginines from its environment.

IMPORTANCE
Methylated arginine residues are common constituents of eukaryotic proteins. During proteolysis, methylarginines are released in their free forms and become accessible nutrients for bacteria to utilize as growth substrates. In order to have a clearer and better understanding of this process, we explored methylarginine utilization in the metabolically versatile bacterium
Pseudomonas aeruginosa
PAO1. Our results show that the transcriptional regulator DdaR (PA1196) and the sigma factor RpoN positively regulate expression of dimethylarginine dimethylaminohydrolases (DDAHs) in response to exogenous methylarginines. DDAH is the central enzyme of methylarginine degradation, and its transcriptional regulation by DdaR-RpoN is expected to be conserved among
P. aeruginosa
strains.
Role of Cyclic Di-GMP and Exopolysaccharide in Type IV Pilus Dynamics
Authors: Ribbe Jan , Baker Amy E. , Euler Sebastian , O'Toole George A. , Maier Berenike 
Published: February 2017

ABSTRACT

For
Pseudomonas aeruginosa
, levels of cyclic di-GMP (c-di-GMP) govern the transition from the planktonic state to biofilm formation. Type IV pili (T4P) are crucial determinants of biofilm structure and dynamics, but it is unknown how levels of c-di-GMP affect pilus dynamics. Here, we scrutinized how c-di-GMP affects molecular motor properties and adhesive behavior of T4P. By means of retraction, T4P generated forces of ∼30 pN. Deletion mutants in the proteins with known roles in biofilm formation, swarming motility, and exopolysaccharide (EPS) production (specifically, the diguanylate cyclases
sadC
and
roeA
or the c-di-GMP phosphodiesterase
bifA
) showed only modest effects on velocity or force of T4P retraction. At high levels of c-di-GMP, the production of exopolysaccharides, particularly of Pel, is upregulated. We found that Pel production strongly enhances T4P-mediated surface adhesion of
P. aeruginosa
, suggesting that T4P-matrix interactions may be involved in biofilm formation by
P. aeruginosa
. Finally, our data support the previously proposed model of slingshot-like “twitching” motility of
P. aeruginosa
.

IMPORTANCE
Type IV pili (T4P) play various important roles in the transition of bacteria from the planktonic state to the biofilm state, including surface attachment and surface sensing. Here, we investigate adhesion, dynamics, and force generation of T4P after bacteria engage a surface. Our studies showed that two critical components of biofilm formation by
Pseudomonas aeruginosa
, T4P and exopolysaccharides, contribute to enhanced T4P-mediated force generation by attached bacteria. These data indicate a crucial role for the coordinated impact of multiple biofilm-promoting factors during the early stages of attachment to a surface. Our data are also consistent with a previous model explaining why pilus-mediated motility in
P. aeruginosa
results in characteristic “twitching” behavior.
Does achieving the best practice tariff improve outcomes in hip fracture patients? An observational cohort study
Authors: Oakley B , Nightingale J , Moran CG , Moppett IK 
Published: February 2017

ObjectivesTo determine if the introduction of the best practice tariff (BPT) has improved survival of the elderly hip fracture population, or if achieving BPT results in improved survival for an individual.SettingA single university-affiliated teaching hospital.Participants2541 patients aged over 60 admitted with a neck of femur fracture between 2008 and 2010 and from 2012 to 2014 were included, to create two cohorts of patients, before and after the introduction of BPT. The post-BPT cohort was divided into two groups, those who achieved the criteria and those who did not.Primary and secondary outcome measuresPrimary outcomes of interest were differences in mortality across cohorts. Secondary analysis was performed to identify associations between individual BPT criteria and mortality.ResultsThe introduction of BPT did not significantly alter overall 30-mortality in the hip fracture population (8.3% pre-BPT vs 10.0% post-BPT; p=0.128). Neither was there a significant reduction in length of stay (15 days (IQR 9–21) pre-BPT vs 14 days (IQR 11–22); p=0.236). However, the introduction of BPT was associated with a reduction in the time from admission to theatre (median 44 hours pre-BPT (IQR 24–44) vs 23 hours post-BPT (IQR 17–30); p<0.005). 30-day mortality in those who achieved BPT was significantly lower (6.0% vs 21.0% in those who did not achieve-BPT; p<0.005). There was a survival benefit at 1 year for those who achieved BPT (28.6% vs 42.0% did not achieve-BPT; p<0.005). Multivariate logistic regression revealed that of the BPT criteria, AMT monitoring and expedited surgery were the only BPT criteria that significantly influenced survival.ConclusionsThe introduction of the BPT has not led to a demonstrable improvement in outcomes at organisational level, though other factors may have confounded any benefits. However, patients where BPT criteria are met appear to have improved outcomes.
Optimization of oestradiol assays to improve utility in an in vitro fertilization setting
Authors: Peavey M , Akbas N , Gibbons W , Zarutskie P , Devaraj S 
Published: February 2017

Background The measurement of oestradiol is an integral component for the management of ovarian stimulation for in vitro fertilization. Automated immunoassays offer fast assay times and high throughput, with less sensitivity and specificity. The aim of this study is to optimize the oestradiol assay in patients undergoing ovarian stimulation for in vitro fertilization via comparison of oestradiol values obtained using two immunoassays compared with mass spectrometry. Methods Patients undergoing ovarian stimulation were prospectively recruited. Serum samples were analysed with ADVIA Centaur® CP Immunoassay, Abbott Architect i1000® immunoassay and AB Sciex 5500 liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems. Per cent bias was determined for each system to report the average tendency of the values to be larger or smaller than the LC-MS/MS value. Linear regression of total follicular volume and oestradiol was computed. Results The ADVIA Centaur® CP assay had a positive bias of 20% compared with LC-MS/MS, while the Architect i1000® had a non-significant, negative bias of 0.3%. With regression fit, a clear, positive relationship was seen between follicular volume and oestradiol. The Architect i1000® assay had a greater correlation (R2 = 0.46) compared with Centaur® CP (R2 = 0.36), when oestradiol values were >1000 pg/mL (3670 pmol/L). Conclusions The Abbott Architect i1000® oestradiol assay exhibits greater agreement with LC-MS/MS and exhibited better correlation to follicular volume when oestradiol values are >1000 pg/mL (3670 pmol/L), prompting a change in the clinic’s oestradiol platform. Attention to assay quality assurance via LC-MS/MS can improve the oestradiol accuracy and permit more informed clinical decisions for improved patient outcomes.
Caeruloplasmin oxidase activity: measurement in serum by use of o-dianisidine dihydrochloride on a microplate reader
Authors: Stepien Karolina M , Guy Mark 
Published: February 2017

Background The enzymatic method of caeruloplasmin measurement is based on copper-dependent oxidase activity. The advantage of the oxidase determination is that it has a much lower detection limit compared with immunoassay-based methods. It has found its application in both the diagnosis of Wilson’s disease and also in the monitoring of patients’ response to treatment. Methods The method previously described in literature was adapted for use on a 96-well plate. Caeruloplasmin oxidase activity results were derived from the equation: caeruloplasmin oxidase activity = (A15−A5) × 185 U/L. Results Repeatability (intra-batch) imprecision ranged from 6 to 15% and intermediate (inter-batch) imprecision varied from 7 to 16% for caeruloplasmin oxidative activities of 14, 29, 45 and 99 U/L. Between 3 and 92 U/L, the assay appeared linear with a regression coefficient R2 = 0.9958. The lower limit of quantification was 4 U/L. Samples were stable over a five-week period at 4℃ and for at least four freeze–thaw cycles. There was a statistically significant difference between the areas under ROC curve for copper-to-caeruloplasmin ratios between caeruloplasmin oxidative activity and immunoassay-based methods ( P < 0.0171). The reference interval for caeruloplasmin activity was determined to be 12–166 U/L. Conclusions Using the oxidative assay provides a cost-effective means of estimating caeruloplasmin concentrations. The method is easily adaptable to a 96-well plate format that facilitates high throughput of samples in a busy laboratory. The enzymatic method is more sensitive and specific for differentiating between Wilson’s and non-Wilson’s when compared with immunoassay-based methods.
Cervical and Ocular VEMP Testing in Diagnosing Superior Semicircular Canal Dehiscence
Authors: Hunter Jacob B. , Patel Neil S. , O’Connell Brendan P. , Carlson Matthew L. , Shepard Neil T. , McCaslin Devin L. , Wanna George B. 
Published: February 2017

ObjectiveTo determine the sensitivity and specificity of ocular and cervical vestibular evoked myogenic potentials (VEMPs) in the diagnosis of superior semicircular canal dehiscence (SCD) and to describe the VEMP response characteristics that are most sensitive to SCD and compare the findings to previous reports.Study DesignCase series with chart review.SettingTwo tertiary neurotologic referral centers.Subjects and MethodsCervical and ocular VEMP peak‐to‐peak amplitudes and thresholds from 39 adult patients older than 18 years with surgically confirmed SCD were compared with 84 age‐matched controls.ResultsUsing receiver operating characteristic (ROC) curves, cervical VEMP (cVEMP) amplitudes, cVEMP thresholds, and ocular VEMP (oVEMP) amplitudes had areas under the curve of 0.731, 0.912, and 0.856, respectively, all of which were statistically significant (P <. 0001). For cVEMP thresholds, at the clinical equivalent ≤85‐dB normalized hearing level (nHL) threshold, the sensitivity and specificity were 97.3% and 31.3%, respectively. At the ≤70‐dB nHL threshold, the sensitivity and specificity were 73.0% and 94.0%, respectively. For oVEMP amplitudes >12.0 µV, the sensitivity and specificity were 78.6% and 81.7%, respectively.ConclusionData from this multicenter study suggest that both cVEMP thresholds and oVEMP amplitudes remain good diagnostic tests for identifying SCD, with each test dependent on a number of factors. The sensitivity and specificity of these individual tests may vary slightly between centers depending on testing parameters used.
Comparison of ACL Strain in the MCL-Deficient and MCL-Reconstructed Knee During Simulated Landing in a Cadaveric Model
Authors: Mancini Eric J. , Kohen Robert , Esquivel Amanda O. , Cracchiolo Allison M. , Lemos Stephen Edward 
Published: February 2017

Background: Noncontact anterior cruciate ligament (ACL) injury after valgus landing has been reported and studied biomechanically. However, the role of the medial collateral ligament (MCL) in dissipating these forces has not been fully elucidated. Purpose/Hypothesis: The purpose of this study was to investigate the role that the MCL plays in ACL strain during simulated landing. The hypothesis was that ACL strain would increase significantly in MCL-incompetent knees compared with the native knee and that reconstructing the MCL would return the values to those of the intact knee. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen human cadaveric knees were used in this study. A materials testing machine applied a force of 2× body weight over 60 milliseconds to simulate landing after a jump. The knees were tested in 12 loading conditions, consisting of full extension or 15° of flexion combined with 7° of valgus or neutral alignment while the tibia was in external rotation, neutral rotation, or internal rotation. This test procedure was repeated on each specimen with the MCL transected and reconstructed. The superficial and deep MCL was transected along with the posterior oblique ligament, which was thought to simulate a worst case scenario. The MCL was reconstructed by use of semitendinosus and gracilis tendon grafts. Results: During internal rotation at 0° of flexion and 0° of valgus, both the intact ( P = .005) and the reconstructed ( P = .004) MCL states placed significantly lower strain on the ACL than did the transected MCL. The reconstructed MCL state at 0° of flexion and 7° of valgus ( P = .049) along with 15° of flexion and 0° of valgus ( P = .020) also placed significantly lower strain on the ACL than did the transected MCL. For external rotation testing at 0° of flexion and 7° of valgus, the reconstructed MCL state placed significantly lower strain on the ACL than did the transected MCL ( P = .039). Finally, during neutral rotation, the ACL strain at 0° of valgus and 0° of flexion, and at 7° of valgus and 0° of flexion was significantly lower for the MCL-intact groups ( P < .028) and MCL-reconstructed groups ( P < .016) than the MCL-transected groups. Conclusion: The current findings demonstrate that during valgus landing, a knee with an incompetent MCL puts the ACL under increased strain. These values are highest in full extension with the tibia in internal and neutral rotation. This increased strain can be reduced to baseline levels with reconstruction. Clinical Relevance: A knee with an incompetent MCL puts the ACL under increased strain. Once the MCL has healed in an elongated manner, MCL reconstruction should be considered.
A Qualitative Study of Experiences with and Perceptions regarding Long-Acting Injectable Antipsychotics: Part I—Patient Perspectives
Authors: Iyer Srividya , Banks Nicola , Roy Marc-André , Tibbo Phil , Williams Richard , Manchanda Rahul , Chue Pierre , Malla Ashok 
Published: February 2017

Objective Despite the well-acknowledged problem of poor adherence to antipsychotic (AP) medication, long-acting injectables (LAIs) that could improve adherence are underused in Canada. Attitudes concerning LAIs among patients and psychiatrists may contribute to this underuse. Our objective was to investigate perceptions of and attitudes toward LAIs among patients in Canada. Method Focus groups were conducted with 34 patients with a diagnosis of schizophrenia spectrum psychoses in 4 Canadian provinces. The focus groups inquired about experiences with and attitudes toward LAI APs. The sessions were audiotaped and transcribed verbatim, and transcripts were coded using a combination of deductive and inductive methods. Results Four themes emerged: awareness of and knowledge about LAIs; perceptions about LAIs; cost and convenience considerations; and issues arising from the coercive context under which LAIs were often prescribed. Nine patients had never heard about LAIs, and some others reported not having understood what was discussed with them regarding LAIs. Patients had typically heard about LAIs in either a context of coercion or of medication nonadherence. Patients had positive and negative perceptions concerning LAIs. The positive perceptions centred on relapse prevention and reduced effort in ensuring adherence, and the negative perceptions centred on financial costs and the inconvenience of appointments to receive injections. Conclusion To enhance LAI usage, some of the issues that need to be addressed are the inadequacy of information given to patients, the element of coercion involved in LAI introduction, the pragmatic barriers to LAI uptake by patients, and negative subjective perceptions about LAIs.
Legal complaints about midwives and the impact on the profession
Authors: Peyman Akram , Nayeri Nahid Dehghan , Bandboni Mohammad Esmaeilpour , Moghadam Zahra Behboodi 
Published: February 2017

Introduction: Midwives play an important role in maintaining and increasing women’s health and well-being. Training professional midwives is one of the main policies of any healthcare system. Since the number of complaints against midwives has increased recently, this study was conducted to explore the perspectives of midwives regarding patients’ complaint to authorities and their impacts on the profession of midwifery. Methods: Being conducted in 2013, this qualitative study was the first of its type in Iran. Data were collected through in-depth semi-structured interviews with 14 midwives working in different cities across the country. The participants were selected using a purposive sampling method. Interviews were transcribed verbatim and analyzed following a qualitative content analysis approach. Written text was then coded, and themes were extracted from the data. Ethical considerations: The study was conducted with midwives’ free informed consent and was approved by Ethics Committee of Tehran University of Medical Sciences. Findings: By analyzing the data, four main themes regarding the impact of complaint on midwifery profession were developed. These included the following: “dissatisfied of midwifery, professional deviation, obsession with work, and weakening of the professional status.” Conclusion: The experience of patients’ complaint to legal authorities against midwives was described, by participants, as a painful experience. Lack of midwives’ knowledge about professional rules and litigation process created many problems for them and could negatively affect their practice and the society’s attitude toward midwifery. Thus, we suggest that in order to prevent such problems, midwives and midwifery students should be educated regarding factors that have the potential to create such problems and also prevention strategies.
The evolution of psychoanalytic thought: a brief view through the lens of Western art and history: Freud and beyond
Authors: Stavovy Tania 
Published: February 2017

Objective: The aim of this paper is to explore the diversity and progress in psychoanalysis and psychotherapy post-Sigmund Freud from the perspective of Western art. Since 1900 the shift from one-person psychology to the more contemporary two-person psychology is reflected in the creativity of artists, particularly in their depiction of the mother–infant relationship. Conclusion: An alternative perspective in understanding the evolution of Man’s nature can be drawn from a discourse between art, history and psychoanalytic thought. Using art as evidence that reflects concurrent changes in psychoanalytic thought is a stimulating way to engage trainee psychiatrists and psychiatrists in their exploration of human nature.