bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensive care unit nurses' knowledge of medication administration via enteral tubes
Authors: Sari Dilek , Kadifeli Derya , Akbiyik Ayşe , Taşkiran Nihal
Published: February 2018

Background

Medication administration via enteral tubes is a complex and key application for which nurses in intensive care units are responsible.

Aim

The aim of this study was to evaluate drug administrations via enteral tubes by nurses in intensive care units.

Methods

This research was conducted using a descriptive and cross‐sectional research design. The study was conducted with 289 nurses at intensive care units in hospitals in İzmir, Turkey. The data of the study were collected with the ‘Sociodemographic Information Form’ and the ‘Enteral Medication Administrations Questionnaire’, which was designed in accordance with the literature and consists of questions on interventions before, during and following medication administrations via enteral tubes.

Results

It was found that more than half the nurses (62.3%) use nasogastric tubes for medication administrations and that all of them use the enteral way for the administration of medications in the form of tablets, while 58.8% use this method to administer the medications in the form of enteric‐coated tablets. It was determined that approximately half the nurses (52.6%) apply more than one medication separately, and a majority (84.1%) use tap water to wash the enteral tube.

Conclusions

Enteral medication administration practices are inconsistent. Some nurses use unsafe practices and may therefore compromise patient care.

Relevance to clinical practice

Conduction of education programmes on medication administration via enteral tubes for intensive care unit nurses is important in improving nurses' knowledge.
Mandibular stability after sagittal split ramus osteotomy without post‐operative maxillomandibular fixation in the treatment of prognathic patients with symmetric mandibles
Authors: Harada K. , Watanabe M. , Okada Y. , Enomoto S.
Published: February 2018

This study was designed to examine post‐operative stability in prognathic patients with symmetric lower jaws who underwent sagittal split ramus osteotomy (SSRO) of the mandible without post‐operative maxillomandibular fixation (MMF). Twenty prognathic patients with symmetric mandibles were investigated. An appliance for repositioning the proximal segment and titanium screw fixation was applied in all patients. Ten patients underwent post‐operative MMF with stainless steel wire (mean duration, 9.6 days) and intermaxillary rubber traction after removal of the MMF (Group I), and the remaining ten underwent intermaxillary rubber traction only (Group II) post‐operatively. Cephalograms were obtained 2–3 days post‐operatively, and 3, 6, and 12 months after surgery. Changes in the positions of upper incisors (U‐1), lower incisors (L‐1), B‐point, and pogonion were examined on lateral cephalograms. In the early stages of follow‐up, decreases in the overbite tended to be more marked in Group I than in Group II, and the forward movement of each standard point was significantly larger in Group I than in Group II. No significant differences, however, were revealed between the two groups at 12 months after surgery. Forward movement of anterior cephalometric landmarks, post‐operatively, in Group II were significant, however, this pattern differed from Group I, in which big changes occurred in the early stages after surgery. Although the patterns of post‐operative changes in the two groups are different, there are no significant differences in their post‐operative stability in long‐term follow‐up. Therefore, post‐operative MMF may be avoided when prognathic patients with symmetric mandibles undergo SSRO with an appliance for repositioning the proximal segment and titanium screw fixation.
The rationale, evolution and clinical application of the self‐ligating bracket
Authors: Damon D.H.
Published: February 2018

There is ample evidence in the literature that conventional orthodontic mechanics while intended to move teeth efficiently rarely achieve atraumatic remodeling of periodontal tissues. The vascular supply is often interrupted, which in turn affects the oxidative metabolism. Moreover, teeth splinted in groups do not appear to move as efficiently as single teeth. The novel bracket design and treatment regimen described in this report allow teeth to move individually, yet stay within a group. The self‐ligating bracket design allows for rapid leveling because teeth drift along the path of least resistance with little or no friction between the bracket and slot of the wire. The hinge mechanism eliminates much of the friction created by the conventional wire or latex ties used to secure the archwire in the bracket slot. Thus, sliding mechanics is achieved in the true sense of the word. This system is capable of increasing the appointment intervals, and possibly reducing the overall treatment time.
Dentofacial morphology and upper respiratory function in 8‐10‐year‐old children
Authors: Shanker Shiva , Beck Frank M. , Allgair Edwin , Vig Peter S. , Vig Katherine W.L.
Published: February 2018

Mouth breathing has been associated with many unfavorable sequelae, the most significant of which are features such as excessively long and tapered (dolicofacial) face form, increased lower face height, and narrow maxillary arch form. The aim of this preliminary study was to assess the nature of associations between selected dentofacial morphological variables and respiratory mode as measured by percent nasality (%N), as part of an ongoing longitudinal study. Ninety‐eight normal children (mean age = 8.95 years) were tested using a modified version of the Simultaneous Nasal and Oral Respirometric Technique for determining %N. Selected dentofacial morphological variables including total and lower anterior face heights, face width, and palatal arch width were measured. Statistical analysis was performed to test the strength of association between the measured dentofacial variables and %N.

Small associations between morphologic features and respiratory mode were found, but none were statistically significant.
Understanding orthodontic treatment satisfaction from the patients' perspective: a qualitative approach
Authors: Bennett M. Elizabeth , Tulloch J.F. Camilla
Published: February 2018

The present study examines treatment satisfaction from the patients' perspective, with special emphasis on the differences between satisfaction with the treatment process (living with orthodontic appliances), satisfaction with office visits, and satisfaction with the treatment outcome. Qualitative data from focused interviews are used to support the notion that treatment satisfaction is a multi‐faceted construct, with different meanings depending on what aspect of treatment is considered.
Quantitative description of overjet and overbite and their relationship with the craniofacial morphology
Authors: Ioannidou I. , Gianniou E. , Koutsikou T. , Kolokithas G.
Published: February 2018

This study was designed to explore whether overjet and overbite relationships might be correlated with the anteroposterior and vertical craniofacial dimensions. The material used to test this hypothesis was lateral cephalometric radiographs from 92 adults (49 women and 43 men) with Angle Class I molar and canine relationships and a harmonious profile. Data were analyzed using the t‐test, Kendall's tau‐b correlation and cluster analysis. The results revealed that a) women exhibit an increased overjet compared to men, and smaller vertical facial dimensions; b) there is a significant correlation between overjet and overbite, overbite and posterior facial height, and overbite and mandibular angle; c) in the two groups of individuals that were separated on the basis of overjet and overbite, only the mandibular plane exhibited a statistical difference between the two groups: groups with small values for overjet and overbite possess high mandibular angles and a decreased mandibular plane angle accompanies large values for overjet and overbite; d) groups separated on the basis of mandibular plane angle were not independent from the groups separated on the basis of overjet and overbite. In summary, occlusal characteristics are not found to be associated with any particular skeletal pattern.
Germination characteristics of Rhinanthus minor influence field emergence, competitiveness and potential use in restoration projects
Authors: Marin M. , Laverack G. , Matthews S. , Powell A. A.
Published: February 2018

The facultative root hemi‐parasite Rhinanthus minor is often used in grassland habitat restoration projects to regulate ecosystem structure and function. Its impact on community productivity and diversity as a function of resource supply, sward composition and management has been widely investigated. However, there is a lack of information about the possible influence of seed quality on the efficacy of the hemi‐parasite.

Ten seed lots from commercial sources were sown in the field and their germination characteristics investigated in the laboratory. Seeds from four lots were also germinated and sown in pots alongside plants of two host species, Lotus corniculatus and Holcus lanatus. Plant establishment, height and flowering density were evaluated for the hemi‐parasite, while plant biomass was measured for both R. minor and its host.

Two aspects of seed quality influenced the field emergence of seed lots of R. minor, the radicle emergence (%) and the length of the lag period from the beginning of imbibition to germination (mean germination time), which indicates seed vigour. A longer lag period (lower vigour) was associated with higher levels of seedling mortality and lower plant vigour, in terms of plant height and biomass accumulation and was also reflected in the parasitic impact of the seed lots.

Seed quality, specifically germination and vigour, can influence the establishment, survival, subsequent plant productivity and parasitic impact of R. minor in vegetation restoration projects. Seed quality is discussed as a key factor to consider when predicting the impact of the hemi‐parasite on community productivity and diversity.
Alpha event‐related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study
Authors: Hata Masahiro , Kurimoto Ryu , Kazui Hiroaki , Ishii Ryouhei , Canuet Leonides , Aoki Yasunori , Ikeda Shunichiro , Azuma Shingo , Suehiro Takashi , Sato Shunsuke , Suzuki Yukiko , Kanemoto Hideki , Yoshiyama Kenji , Iwase Masao , Ikeda Manabu
Published: February 2018

Background

The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis.

Methods

Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age‐matched normal subjects were recruited. We investigated alterations in the ratio of event‐related synchronization (ERS) in the alpha band after eye‐closing.

Results

Although the averaged ratio change of alpha ERS after eye‐closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto‐occipital cortex compared to Alzheimer's disease patients or normal controls.

Conclusion

Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye‐closing is a brain electromagnetic feature of DLB.
Characterization of anti‐Müllerian hormone in a case of bovine male pseudohermaphroditism
Authors: Kitahara G , El‐Sheikh Ali H , Teh APP , Hidaka Y , Haneda S , Mido S , Yamaguchi R , Osawa T
Published: February 2018

Contents

The current report aimed to characterize plasma anti‐Müllerian hormone (AMH) in bovine male pseudohermaphroditism. The blood AMH concentration in a Japanese Black male pseudohermaphrodite calf was compared with pre‐ and post‐pubertal male and female calves and castrated calves. The concentration in the case was higher than in post‐pubertal males, castrated males, and pre‐ and post‐pubertal female calves (p < .05), but similar to that in pre‐pubertal male calves. After extraction of the testes, the concentration in the case dropped to a certain extent. The extracted testes expressed AMH, as detected by immunohistochemistry. This study is the first to show the characterization of AMH in a male pseudohermaphrodite calf. AMH levels in peripheral blood might be useful to diagnose male pseudohermaphroditism in cattle.
A rare case of Epstein‐Barr virus‐associated hepatosplenic smooth muscle tumors after kidney transplantation
Authors: Pircher C. , Schneeberger S. , Boesmueller C. , Agaimy A. , Zoller H. , Bale R. , Henninger B. , Mayer G. , Neuwirt H.
Published: February 2018

A 27‐year old caucasian male was diagnosed 2.7 years after kidney transplantation with Epstein‐Barr virus (EBV)‐associated smooth muscle tumors in liver and spleen. The reduction in immunosuppression and conversion from tacrolimus to sirolimus did not lead to a regression of the tumors. Additionally, the patient developed a cellular rejection of his renal allograft, which was successfully treated. A combined approach with stereotactic radiofrequency ablation (SRFA) and surgical resection was effective in the treatment of the tumors.
Efficacy and safety of sarolaner against generalized demodicosis in dogs in European countries: a non‐inferiority study
Authors: Becskei Csilla , Cuppens Otto , Mahabir Sean P.
Published: February 2018

Background

Treatment of canine demodicosis can be challenging; new treatments are always being sought.

Objective

The efficacy of sarolaner was evaluated in comparison with a moxidectin/imidacloprid topical product against generalized demodicosis in dogs in a randomized, single‐masked, multi‐centre field study.

Animals

Client‐owned dogs were treated monthly with oral sarolaner (n= 53) or with weekly/monthly topical moxidectin/imidacloprid (n= 28).

Methods

Mites were counted monthly in deep skin scrapings and the severity of skin lesions was evaluated. Dogs completed the study when no live mites were found on two consecutive monthly skin scrapings or on day 180 at the latest (study end).

Results

Parasitological cure, defined as the first time that no live mites were found in the skin scrapings, was achieved in 92.9% and 100% of the dogs after three and no more than five monthly treatments with sarolaner (respectively). In the moxidectin/imidacloprid group, 77.3% and 91.7% of the dogs were cured after three and six months, respectively. Parasitological cure rate for sarolaner was non‐inferior to moxidectin/imidacloprid on day 60. Mite counts were reduced by 77.2%, 95.0%, 98.5%, 99.0%, 100% and 100% in the sarolaner group and by 68.0%, 88.4%, 91.1%, 92.7%, 73.9% and 82.2% in the moxidectin/imidacloprid group, on days 30, 60, 90, 120, 150 and 180, respectively, compared to pre‐treatment counts. The skin lesions improved throughout the study; the total affected body surface decreased by 94% in the sarolaner and by 72% in the moxidectin/imidacloprid group. There were no treatment‐related adverse events.

Conclusions

Monthly oral administration of sarolaner was safe and highly effective in the treatment of generalized demodicosis in dogs.
Perceiving foreign-accented speech with decreased spectral resolution in single- and multiple-talker conditions
Authors: Kapolowicz Michelle R. , Montazeri Vahid , Assmann Peter F.
Published: February 2018

To determine the effect of reduced spectral resolution on the intelligibility of foreign-accented speech, vocoder-processed sentences from native and Mandarin-accented English talkers were presented to listeners in single- and multiple-talker conditions. Reduced spectral resolution had little effect on native speech but lowered performance for foreign-accented speech, with a further decrease in multiple-talker conditions. Following the initial exposure, foreign-accented speech with reduced spectral resolution was less intelligible than unprocessed speech in both single- and multiple-talker conditions. Intelligibility improved with extended exposure, but only for single-talker conditions. Results indicate a perceptual impairment when perceiving foreign-accented speech with reduced spectral resolution.
Growth, Maturation, and Exercise During Youth—The Year That Was 2017
Authors: Jürimäe Jaak
Published: February 2018

For “The Year That Was 2017,” I have selected 3 papers in the area of growth, maturation, and exercise during youth. The first paper has been chosen because it provides for the first time the relative age, maturation, and anthropometric biases on position allocation in elite youth soccer players participating in talent identification programs in professional soccer league. Specific anthropometrical attributes characterized playing positions with a bias toward these athletes who are comparatively tall and heavy for their age already in younger ages, whereas position-specific physical attributes do not become apparent until the later stages of talent development. The second paper was selected because it provides a unique perspective on the contributions of different types of sport activities to the development of soccer performance. This paper demonstrated that early specialization and concentration on one sport only during growth is not beneficial in elite youth soccer. In contrast, variable early sporting experience, and not different physiological parameters, facilitates subsequent soccer performance development. The third paper provided some evidence that the consequence of physical activity during adolescence can be far reaching as physical activity might not only predict academic success during compulsory basic education but also boost educational outcomes in adulthood.
Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam
Authors: Nukaga Michiyoshi , Papp-Wallace Krisztina M. , Hoshino Tyuji , Lefurgy Scott T. , Bethel Christopher R. , Barnes Melissa D. , Zeiser Elise T. , Johnson J. Kristie , Bonomo Robert A.
Published: February 2018

Ceftazidime-avibactam is a “second-generation” β-lactam–β-lactamase inhibitor combination that is effective against
Enterobacteriaceae
expressing class A extended-spectrum β-lactamases, class A carbapenemases, and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases, is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in the
Citrobacter
AmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active-site topologies affect avibactam inhibition, we tested a panel of clinical
Enterobacteriaceae
isolates producing
bla
FOX
using ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producing
bla
FOX
; two isolates, one expressing
bla
FOX-4
and the other producing
bla
FOX-5
, displayed an MIC of 16 μg/ml for the combination. FOX-4 possessed a
k
2
/
K
value of 1,800 ± 100 M
−1
· s
−1
and an off rate (
k
off
) of 0.0013 ± 0.0003 s
−1
. Mass spectrometry showed that the FOX-4–avibactam complex did not undergo chemical modification for 24 h. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5-Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the
Pseudomonas
-derived cephalosporinase 1 (PDC-1)–avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen-bonding interactions. This observation supports findings from the inhibition analysis of FOX-4; FOX-4 possessed the highest

K
d

(dissociation constant) value (1,600 nM) for avibactam compared to other AmpCs (7 to 660 nM). Medicinal chemists must consider the properties of extended-spectrum AmpCs, such as the FOX β-lactamases, for the design of future diazabicyclooctanes.
Targeting the Nonmevalonate Pathway in Burkholderia cenocepacia Increases Susceptibility to Certain β-Lactam Antibiotics
Authors: Sass Andrea , Everaert Annelien , Van Acker Heleen , Van den Driessche Freija , Coenye Tom
Published: February 2018

The nonmevalonate pathway is the sole pathway for isoprenoid biosynthesis in
Burkholderia cenocepacia
and is possibly a novel target for the development of antibacterial chemotherapy. The goals of the present study were to evaluate the essentiality of
dxr
, the second gene of the nonmevalonate pathway, in
B. cenocepacia
and to determine whether interfering with the nonmevalonate pathway increases susceptibility toward antibiotics. To this end, a rhamnose-inducible conditional
dxr
knockdown mutant of
B. cenocepacia
strain K56-2 (
B. cenocepacia
K56-2
dxr
) was constructed, using a plasmid which enables the delivery of a rhamnose-inducible promoter in the chromosome. Expression of
dxr
is essential for bacterial growth; the growth defect observed in the
dxr
mutant could be complemented by expressing
dxr in trans
under the control of a constitutive promoter, but not by providing 2-
C
-methyl-
d
-erythritol-4-phosphate, the reaction product of DXR (1-deoxy-
d
-xylulose 5-phosphate reductoisomerase).
B. cenocepacia
K56-2
dxr
showed markedly increased susceptibility to the β-lactam antibiotics aztreonam, ceftazidime, and cefotaxime, while susceptibility to other antibiotics was not (or was much less) affected; this increased susceptibility could also be complemented by
in trans
expression of
dxr
. A similarly increased susceptibility was observed when antibiotics were combined with FR900098, a known DXR inhibitor. Our data confirm that the nonmevalonate pathway is essential in
B. cenocepacia
and suggest that combining potent DXR inhibitors with selected β-lactam antibiotics is a useful strategy to combat
B. cenocepacia
infections.
Single-Molecule Tracking of DNA Translocases in Bacillus subtilis Reveals Strikingly Different Dynamics of SftA, SpoIIIE, and FtsA
Authors: El Najjar Nina , El Andari Jihad , Kaimer Christine , Fritz Georg , Rösch Thomas C. , Graumann Peter L.
Published: February 2018

Like many bacteria,
Bacillus subtilis
possesses two DNA translocases that affect chromosome segregation at different steps. Prior to septum closure, nonsegregated DNA is moved into opposite cell halves by SftA, while septum-entrapped DNA is rescued by SpoIIIE. We have used single-molecule fluorescence microscopy and tracking (SMT) experiments to describe the dynamics of the two different DNA translocases, the cell division protein FtsA and the glycolytic enzyme phosphofructokinase (PfkA), in real time. SMT revealed that about 30% of SftA molecules move through the cytosol, while a fraction of 70% is septum bound and static. In contrast, only 35% of FtsA molecules are static at midcell, while SpoIIIE molecules diffuse within the membrane and show no enrichment at the septum. Several lines of evidence suggest that FtsA plays a role in septal recruitment of SftA: an
ftsA
deletion results in a significant reduction in septal SftA recruitment and a decrease in the average dwell time of SftA molecules. FtsA can recruit SftA to the membrane in a heterologous eukaryotic system, suggesting that SftA may be partially recruited via FtsA. Therefore, SftA is a component of the division machinery, while SpoIIIE is not, and it is otherwise a freely diffusive cytosolic enzyme
in vivo
. Our developed SMT script is a powerful technique to determine if low-abundance proteins are membrane bound or cytosolic, to detect differences in populations of complex-bound and unbound/diffusive proteins, and to visualize the subcellular localization of slow- and fast-moving molecules in live cells.

IMPORTANCE
DNA translocases couple the late events of chromosome segregation to cell division and thereby play an important role in the bacterial cell cycle. The proteins fall into one of two categories, integral membrane translocases or nonintegral translocases. We show that the membrane-bound translocase SpoIIIE moves slowly throughout the cell membrane in
B. subtilis
and does not show a clear association with the division septum, in agreement with the idea that it binds membrane-bound DNA, which can occur through cell division across nonsegregated chromosomes. In contrast, SftA behaves like a soluble protein and is recruited to the division septum as a component of the division machinery. We show that FtsA contributes to the recruitment of SftA, revealing a dual role of FtsA at the division machinery, but it is not the only factor that binds SftA. Our work represents a detailed
in vivo
study of DNA translocases at the single-molecule level.
Influence of Eimeria falciformis Infection on Gut Microbiota and Metabolic Pathways in Mice
Authors: Huang Guangping , Zhang Sixin , Zhou Chunxue , Tang Xiaoli , Li Chao , Wang Chaoyue , Tang Xinming , Suo Jingxia , Jia Yonggen , El-Ashram Saeed , Yu Zhengquan , Cai Jianping , Gupta Nishith , Suo Xun , Liu Xianyong
Published: February 2018

Coccidiosis, caused by different species of
Eimeria
parasites, is an economically important disease of poultry and livestock worldwide. Here we report previously unknown alterations in the gut microbes and metabolism of BALB/c mice infected with
Eimeria falciformis
. Specifically, we observed a significant shift in the abundance of cecal bacteria and disrupted metabolism in parasitized animals. The relative abundances of
Lachnospiraceae
bacterium NK4A136,
Ruminiclostridium
,
Alistipes
, and
Lactobacillus
declined in response to
E. falciformis
infection, whereas
Escherichia
,
Shigella
,
Helicobacter
,
Klebsiella
, and
Bacteroides
were increased. Carbohydrate and amino acid metabolites in the serum samples of infected mice were significantly altered compared to naïve controls. Levels of amino acids, including asparagine, histidine,
l
-cysteine, tryptophan, lysine, glycine, serine, alanine, proline, ornithine, methionine, and valine, decreased on day 7 postinfection before returning to baseline on day 14. In addition, increased levels of indolelactate and mannitol and a reduced amount of oxalic acid indicated impaired carbon metabolism upon parasitic infection. These data demonstrate that intestinal coccidial infection perturbs the microbiota and disrupts carbon and nitrogen metabolism.
A Plasmodium Parasite with Complete Late Liver Stage Arrest Protects against Preerythrocytic and Erythrocytic Stage Infection in Mice
Authors: Vaughan Ashley M. , Sack Brandon K. , Dankwa Dorender , Minkah Nana , Nguyen Thao , Cardamone Hayley , Kappe Stefan H. I.
Published: February 2018

Genetically attenuated malaria parasites (GAP) that arrest during liver stage development are powerful immunogens and afford complete and durable protection against sporozoite infection. Late liver stage-arresting GAP provide superior protection against sporozoite challenge in mice compared to early live stage-arresting attenuated parasites. However, very few late liver stage-arresting GAP have been generated to date. Therefore, identification of additional loci that are critical for late liver stage development and can be used to generate novel late liver stage-arresting GAPs is of importance. We further explored genetic attenuation in
Plasmodium yoelii
by combining two gene deletions,
PlasMei2
and
liver-specific protein 2
(
LISP2
), that each cause late liver stage arrest with various degrees of infrequent breakthrough to blood stage infection. The dual gene deletion resulted in a synthetic lethal phenotype that caused complete attenuation in a highly susceptible mouse strain.
P. yoelii
plasmei2
−
lisp2
−
arrested late in liver stage development and did not persist in livers beyond 3 days after infection. Immunization with this GAP elicited robust protective antibody responses in outbred and inbred mice against sporozoites, liver stages, and blood stages as well as eliciting protective liver-resident T cells. The immunization afforded protection against both sporozoite challenge and blood stage challenge. These findings provide evidence that completely attenuated late liver stage-arresting GAP are achievable via the synthetic lethal approach and might enable a path forward for the creation of a completely attenuated late liver stage-arresting
P. falciparum
GAP.
Functional Overlap of
hetP
and
hetZ
in Regulation of Heterocyst Differentiation in Anabaena sp. Strain PCC 7120
Authors: Zhang He , Wang Shuai , Wang Yali , Xu Xudong
Published: February 2018

HetR plays a key role in regulation of heterocyst differentiation and patterning in
Anabaena
. It directly regulates genes involved in heterocyst differentiation (such as
hetP
and
hetZ
), genes involved in pattern formation (
patA
), and many others. In this study, we investigated the functional relationship of
hetP
and
hetZ
and their role in HetR-dependent cell differentiation. Coexpression of
hetP
and
hetZ
from the promoter of
ntcA
, which encodes the global nitrogen regulator, enabled a
hetR
mutant to form heterocysts with low aerobic nitrogenase activity. Overexpression of
hetZ
restored heterocyst differentiation in a
hetP
mutant and vice versa. Overexpression of
hetR
restored heterocyst formation in either a
hetP
or a
hetZ
mutant but not in a
hetZ hetP
double mutant. The functional overlap of
hetP
and
hetZ
was further confirmed by reverse transcription-quantitative PCR (RT-qPCR) and transcriptomic analyses of their effects on gene expression. In addition, yeast two-hybrid and pulldown assays showed the interaction of HetZ with HetR. HetP and HetZ are proposed as the two major factors that control heterocyst formation in response to upregulation of
hetR
.

IMPORTANCE
Heterocyst-forming cyanobacteria contribute significantly to N
2
fixation in marine, freshwater, and terrestrial ecosystems. Formation of heterocysts enables this group of cyanobacteria to fix N
2
efficiently under aerobic conditions. HetR, HetP, and HetZ are among the most important factors involved in heterocyst differentiation. We present evidence for the functional overlap of
hetP
and
hetZ
and for the key role of the HetR-HetP/HetZ circuit in regulation of heterocyst differentiation. The regulatory mechanism based on HetR, HetP, and HetZ is probably conserved in all heterocyst-forming cyanobacteria.
Diagnosing Invasive Candidiasis
Authors: Clancy Cornelius J. , Nguyen M. Hong
Published: February 2018

Cultures are negative in ∼50% of invasive candidiasis. Data are emerging for the performance of nonculture tests such as mannan/antimannan,
Candida albicans
germ tube antibody, 1,3-β-
d
-glucan, PCR, and the T2Candida panel in diagnosing both candidemia and deep-seated candidiasis. In most settings, positive predictive values of nonculture test are low, and negative predictive values are high. For tests to be useful, clinicians must understand the pretest likelihood of invasive candidiasis and test performance for the most common disease manifestation in a given patient. This paper reviews nonculture
Candida
diagnostics and discusses how they might be used effectively in patient care.
Intranasal Live Influenza Vaccine Priming Elicits Localized B Cell Responses in Mediastinal Lymph Nodes
Authors: Jegaskanda Sinthujan , Mason Rosemarie D. , Andrews Sarah F. , Wheatley Adam K. , Zhang Ruijun , Reynoso Glennys V. , Ambrozak David R. , Santos Celia P. , Luke Catherine J. , Matsuoka Yumiko , Brenchley Jason M. , Hickman Heather D. , Talaat Kawsar R. , Permar Sallie R. , Liao Hua-Xin , Yewdell Jonathan W. , Koup Richard A. , Roederer Mario , McDermott Adrian B. , Subbarao Kanta
Published: February 2018

Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination.

IMPORTANCE
We have previously shown that pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust antibody response on subsequent administration of inactivated subunit vaccine (pISV). This is observed even in individuals who had undetectable antibody (Ab) responses following the initial vaccination. To define the mechanistic basis of pLAIV priming, we turned to a nonhuman primate model and performed a detailed analysis of B cell responses in systemic and local lymphoid tissues following prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate model recapitulates the serologic observations from clinical studies. Further, we found that pLAIVs induced robust germinal center B cell responses in the mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals resulted in detection of B cells in the axillary lymph nodes, spleen, and peripheral blood. We demonstrate that intranasally administered pLAIV elicits a highly localized germinal center B cell response in the mediastinal lymph node that is rapidly recalled following pISV boost into germinal center reactions at numerous distant immune sites.
Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov
Authors: Bothwell Laura E , Avorn Jerry , Khan Nazleen F , Kesselheim Aaron S
Published: February 2018

Objectives

This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials.

Design

Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs.

Results

142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs.

Conclusions

Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis.
Is socioeconomic segregation of the poor associated with higher premature mortality under the age of 60? A cross-sectional analysis of survey data in major Indian cities
Authors: Chandola Tarani , Mikkilineni Sitamma , Chandran Anil , Bandyopadhyay Souvik Kumar , Zhang Nan , Bassanesi Sergio Luiz
Published: February 2018

Objectives

Although urbanisation is generally associated with poverty reduction in low-income and middle-income countries, it also results in increased socioeconomic segregation of the poor. Cities with higher levels of socioeconomic segregation tend to have higher mortality rates, although the evidence is based on ecological associations. The paper examines whether socioeconomic segregation of the poor is associated with higher under-60 years (‘premature’) mortality risk in Indian cities and whether this association is confounded by contextual and compositional sociodemographic and socioeconomic factors.

Setting and participants

A population representative sample of over one million from 39 427 households living in 1876 urban wards within 59 Indian districts (cities) from the third (2008) District Level Household Survey (DLHS-3).

Primary outcome and other measures

The outcome was any death under the age of 60 reported by households in the preceding 4years of the DLHS-3. Socioeconomic segregation, estimated at the district (city) level, was measured using an isolation index of the poor and the index of dissimilarity.

Results

Poor households living in cities where the poor were more isolated had higher probabilities of premature mortality than poor households living in cities where the poor were less isolated. In contrast, it did not matter whether rich households lived in more or less socioeconomically segregated cities. A 1 SD increase in the isolation index was associated with an absolute increase of 1.1% in the probability of premature mortality for the poorest households.

Conclusion

Increasing segregation of the poor may result in higher premature mortality. As low-income and middle-income countries become increasingly urbanised, there is a risk that this may lead to increased segregation of the poor as well as increased premature mortality.
Sequelae of multidrug-resistant tuberculosis: protocol for a systematic review and meta-analysis
Authors: Alene Kefyalew Addis , Clements Archie C A , McBryde Emma S , Jaramillo Ernesto , Lonnroth Knut , Shaweno Debebe , Viney Kerri
Published: February 2018

Introduction

The sequelae of multidrug-resistant tuberculosis (MDR-TB) are poorly understood and inconsistently reported. We will aim to assess the existing evidence for the clinical, psychological, social and economic sequelae of MDR-TB and to assess the health-related quality of life in patients with MDR-TB.

Methods and analysis

We will perform a systematic review and meta-analysis of published studies reporting sequelae of MDR-TB. We will search PubMed, SCOPUS, ProQuest, Web of Science and PsychINFO databases up to 5 September 2017. MDR-TB sequelae will include any clinical, psychological, social and economic effects as well as health-related quality of life that occur after MDR-TB treatment or illness. Two researchers will screen the titles and abstracts of all citations identified in our search, extract data, and assess the scientific quality using standardised formats. Providing there is appropriate comparability in the studies, we will use a random-effects meta-analysis model to produce pooled estimates of MDR-TB sequelae from the included studies. We will stratify the analyses based on treatment regimen, comorbidities (such as HIV status and diabetes mellitus), previous TB treatment history and study setting.

Ethics and dissemination

As this study will be based on published data, ethical approval is not required. The final report will be disseminated through publication in a peer-reviewed scientific journal and will also be presented at relevant conferences.

PROSPERO registration number

CRD42017073182.
Severity and management of postabortion complications among women in Zimbabwe, 2016: a cross-sectional study
Authors: Madziyire Mugove Gerald , Polis Chelsea B , Riley Taylor , Sully Elizabeth A , Owolabi Onikepe , Chipato Tsungai
Published: February 2018

Objectives

Abortion complications cause significant morbidity and mortality. We aimed to assess the severity and factors associated with abortion complications (induced or spontaneous), and the management of postabortion care (PAC) in Zimbabwe.

Design

Prospective, facility-based 28 day survey among women seeking PAC and their providers.

Setting

127 facilities in Zimbabwe with the capacity to provide PAC, including all central and provincial hospitals, and a sample of primary health centres (30%), district/general/mission hospitals (52%), private (77%) and non-governmental organisation (NGO) (68%) facilities.

Participants

1002 women presenting with abortion complications during the study period.

Main outcome measures

Severity of abortion complications and associated factors, delays in care seeking, and clinical management of complications.

Results

Overall, 59% of women had complications classified as mild, 19% as moderate, 19% as severe, 3% as near miss and 0.2% died. A median of 47 hours elapsed between experiencing complication and receiving treatment; many delays were due to a lack of finances. Women who were rural, younger, not in union, less educated, at later gestational ages or who had more children were significantly more likely to have higher severity complications. Most women were treated by doctors (91%). The main management procedure used was dilatation and curettage/dilatation and evacuation (75%), while 12% had manual vacuum aspiration (MVA) or electrical vacuum aspiration and 11% were managed with misoprostol. At discharge, providers reported that 43% of women received modern contraception.

Conclusion

Zimbabwean women experience considerable abortion-related morbidity, particularly young, rural or less educated women. Abortion-related morbidity and concomitant mortality could be reduced in Zimbabwe by liberalising the abortion law, providing PAC in primary health centres, and training nurses to use medical evacuation with misoprostol and MVA. Regular in-service training on PAC guidelines with follow-up audits are needed to ensure compliance and availability of equipment, supplies and trained staff.
Differing associations for sport versus occupational physical activity and cardiovascular risk
Authors: Ferrario Marco Mario , Roncaioli Mattia , Veronesi Giovanni , Holtermann Andreas , Clays Els , Borchini Rossana , Cavicchiolo Marco , Grassi Guido , Cesana Giancarlo
Published: February 2018

Objectives

We investigate the independent and interacting long-term associations of occupational physical activity (OPA) and sport physical activity (SpPA) with the incidence of coronary heart disease (CHD) and cardiovascular diseases (CVD; CHD plus ischaemic stroke) in North Italian male workers.

Methods

3574 employed men aged 25–64 years, free of CVD at baseline, recruited in three population-based and one factory-based cohorts, were included in the analysis. The Baecke Questionnaire was used to assess OPA and SpPA in ‘minutes per week’ of moderate or vigorous PA. We estimated the associations between different domains of PA and the endpoints, adjusting for major CVD risk factors, using Cox models.

Results

During a median follow-up of 14 years, 135 and 174 first CHD and CVD events, fatal and non-fatal, occurred. Compared with the intermediate OPA tertile, the HRs for CHD among low and high OPA workers were 1.66 (95% CI 1.06 to 2.59) and 1.18 (0.72 to 1.94), respectively (P value=0.07). Decreasing trends in CHD and CVD rates across increasing levels of SpPA were also found, with an HR for CVD of 0.68 (0.46 to 0.98) for intermediate/recommended SpPA compared with poor SpPA. We also found a statistically significant SpPA-OPA interaction, and the protective effect of SpPA was only found among sedentary workers, for both endpoints. Conversely, high OPA workers with intermediate/recommended SpPA levels had increased CHD and CVD rates compared with the poor SpPA category.

Conclusions

Our results provide further evidence on the health paradox of OPA, with higher CVD rates among workers with intense PA at work. Moreover, the protective effect on CVDs of SpPA is prominent in sedentary workers, but it attenuates and even reverses in moderate and strenuous OPA workers.
Household air pollution and measures of blood pressure, arterial stiffness and central haemodynamics
Authors: Baumgartner Jill , Carter Ellison , Schauer James J , Ezzati Majid , Daskalopoulou Stella S , Valois Marie-France , Shan Ming , Yang Xudong
Published: February 2018

Objective

We evaluated the exposure–response associations between personal exposure to air pollution from biomass stoves and multiple vascular and haemodynamic parameters in rural Chinese women.

Methods

We analysed the baseline information from a longitudinal study in southwestern China. Women’s brachial and central blood pressure and pulse pressure, carotid-femoral pulse wave velocity and augmentation index, and their 48-hour personal exposures to fine particulate matter (PM2.5) and black carbon were measured in summer and winter. We evaluated the associations between exposure to air pollution and haemodynamic parameters using mixed-effects regression models adjusted for known cardiovascular risk factors.

Results

Women’s (n=205, ages 27–86 years) exposures to PM2.5 and black carbon ranged from 14 µg/m3 to 1405 µg/m3 and 0.1–121.8 µg/m3, respectively. Among women aged ≥50 years, increased PM2.5 exposure was associated with higher systolic (brachial: 3.5 mm Hg (P=0.05); central: 4.4 mm Hg (P=0.005)) and diastolic blood pressure (central: 1.3 mm Hg (P=0.10)), higher pulse pressure (peripheral: 2.5 mm Hg (P=0.05); central: 2.9 mm Hg (P=0.008)) and lower peripheral–central pulse pressure amplification (−0.007 (P=0.04)). Among younger women, the associations were inconsistent in the direction of effect and not statistically significant. Increased PM2.5 exposure was associated with no difference in pulse wave velocity and modestly higher augmentation index though the CI included zero (1.1%; 95% CI −0.2% to 2.4%). Similar associations were found for black carbon exposure.

Conclusions

Exposure to household air pollution was associated with higher blood pressure and central haemodynamics in older Chinese women, with no associations observed with pulse wave velocity.