bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gastrointestinal Tract Is a Major Source of Echinocandin Drug Resistance in a Murine Model of Candida glabrata Colonization and Systemic Dissemination
Authors: Healey Kelley R. , Nagasaki Yoji , Zimmerman Matthew , Kordalewska Milena , Park Steven , Zhao Yanan , Perlin David S. 
Published: October 2017

ABSTRACT

Candida
species are a part of the human microbiome and can cause systemic infection upon immune suppression.
Candida glabrata
infections are increasing and have greater rates of antifungal resistance than other species. Here, we present a
C. glabrata
gastrointestinal (GI) colonization model to explore whether colonized yeast exposed to caspofungin, an echinocandin antifungal, develop characteristic resistance mutations and, upon immunosuppression, breakthrough causing systemic infection. Daily therapeutic dosing (5 mg/kg of body weight) of caspofungin resulted in no reduction in fecal burdens, organ breakthrough rates similar to control groups, and resistance rates (0 to 10%) similar to those reported clinically. Treatment with 20 mg/kg caspofungin initially reduced burdens, but a rebound following 5 to 9 days of treatment was accompanied by high levels of resistance (
FKS1
/
FKS2
mutants). Although breakthrough rates decreased in this group, the same
FKS
mutants were recovered from organs. In an attempt to negate drug tolerance that is critical for resistance development, we cotreated mice with daily caspofungin and the chitin synthase inhibitor nikkomycin Z. The largest reduction (3 log) in GI burdens was obtained within 3 to 5 days of 20 mg/kg caspofungin plus nikkomycin treatment. Yet, echinocandin resistance, characterized by a novel Fks1-L630R substitution, was identified following 5 to 7 days of treatment. Therapeutic caspofungin plus nikkomycin treatment left GI burdens unchanged but significantly reduced organ breakthrough rates (20%;
P
< 0.05). Single-dose pharmacokinetics demonstrated low levels of drug penetration into the GI lumen posttreatment with caspofungin. Overall, we show that
C. glabrata
echinocandin resistance can arise within the GI tract and that resistant mutants can readily disseminate upon immunosuppression.
Environmental Survey of Drinking Water Sources in Kampala, Uganda, during a Typhoid Fever Outbreak
Authors: Murphy J. L. , Kahler A. M. , Nansubuga I. , Nanyunja E. M. , Kaplan B. , Jothikumar N. , Routh J. , Gómez G. A. , Mintz E. D. , Hill V. R. 
Published: October 2017

ABSTRACT

In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for
Escherichia coli
, free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of
Salmonella enterica
serovar Typhi.
Escherichia coli
was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained
E. coli
and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained
E. coli
. Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable
E. coli
. While
S
. Typhi was not detected in water samples,
Salmonella
spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission.

IMPORTANCE
Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of
E. coli
or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions.
Potentiating Effect of Mandelate and Lactate on Chemically Induced Germination in Members of
Bacillus cereus Sensu Lato
Authors: Bishop Alistair H. 
Published: October 2017

ABSTRACT

Endospores of the genus
Bacillus
can be triggered to germinate by a limited number of chemicals. Mandelate had powerful additive effects on the levels and rates of germination produced in non-heat-shocked spores of
Bacillus anthracis
strain Sterne,
Bacillus cereus
, and
Bacillus thuringiensis
when combined with
l
-alanine and inosine. Mandelate had no germinant effect on its own but was active with these germinants in a dose-dependent manner at concentrations higher than 0.5 mM. The maximum rate and extent of germination were produced in
B. anthracis
by 100 mM
l
-alanine with 10 mM inosine; this was equaled by just 25% of these germinants when supplemented with 10 mM mandelate. Half the maximal germination rate was produced by 40% of the optimum germinant concentrations or 15% of them when supplemented with 0.8 mM mandelate. Germination rates in
B. thuringiensis
were highest around neutrality, but the potentiating effect of mandelate was maintained over a wider pH range than was germination with
l
-alanine and inosine alone. For all species, lactate also promoted germination in the presence of
l
-alanine and inosine; this was further increased by mandelate. Ammonium ions also enhanced
l
-alanine- and inosine-induced germination but only when mandelate was present. In spite of the structural similarities, mandelate did not compete with phenylalanine as a germinant. Mandelate appeared to bind to spores while enhancing germination. There was no effect when mandelate was used in conjunction with nonnutrient germinants. No effect was produced with spores of
Bacillus subtilis
,
Clostridium sporogenes
, or
C. difficile
.

IMPORTANCE
The number of chemicals that can induce germination in the species related to
Bacillus cereus
has been defined for many years, and they conform to specific chemical types. Although not a germinant itself, mandelate has a structure that is different from these germination-active compounds, and its addition to this list represents a significant discovery in the fundamental biology of spore germination. This novel activity may also have important applied relevance given the impact of spores of
B. cereus
in foodborne disease and
B. anthracis
as a threat agent. The destruction of spores of
B. anthracis
, for example, particularly over large outdoor areas, poses significant scientific and logistical problems. The addition of mandelate and lactate to the established mixtures of
l
-alanine and inosine would decrease the amount of the established germinants required and increase the speed and level of germination achieved. The large-scale application of “germinate to decontaminate” strategy may thus become more practicable.
Genetic Dissection of DivIVA Functions in Listeria monocytogenes
Authors: Kaval Karan Gautam , Hauf Samuel , Rismondo Jeanine , Hahn Birgitt , Halbedel Sven 
Published: October 2017

ABSTRACT

DivIVA is a membrane binding protein that clusters at curved membrane regions, such as the cell poles and the membrane invaginations occurring during cell division. DivIVA proteins recruit many other proteins to these subcellular sites through direct protein-protein interactions. DivIVA-dependent functions are typically associated with cell growth and division, even though species-specific differences in the spectrum of DivIVA functions and their causative interaction partners exist. DivIVA from the Gram-positive human pathogen
Listeria monocytogenes
has at least three different functions. In this bacterium, DivIVA is required for precise positioning of the septum at midcell, it contributes to the secretion of autolysins required for the breakdown of peptidoglycan at the septum after the completion of cell division, and it is essential for flagellar motility. While the DivIVA interaction partners for control of division site selection are well established, the proteins connecting DivIVA with autolysin secretion or swarming motility are completely unknown. We set out to identify
divIVA
alleles in which these three DivIVA functions could be separated, since the question of the degree to which the three functions of
L. monocytogenes
DivIVA are interlinked could not be answered before. Here, we identify such alleles, and our results show that division site selection, autolysin secretion, and swarming represent three discrete pathways that are independently influenced by DivIVA. These findings provide the required basis for the identification of DivIVA interaction partners controlling autolysin secretion and swarming in the future.

IMPORTANCE
DivIVA of the pathogenic bacterium
Listeria monocytogenes
is a central scaffold protein that influences at least three different cellular processes, namely, cell division, protein secretion, and bacterial motility. How DivIVA coordinates these rather unrelated processes is not known. We here identify variants of
L. monocytogenes
DivIVA, in which these functions are separated from each other. These results have important implications for the models explaining how DivIVA interacts with other proteins.
Parental experience of interaction with healthcare professionals during their infant’s stay in the neonatal intensive care unit
Authors: Gallagher Katie , Shaw Chloe , Aladangady Narendra , Marlow Neil 
Published: October 2017

ObjectiveTo explore the experiences of parents of infants admitted to the neonatal intensive care unit towards interaction with healthcare professionals during their infants critical care.DesignSemi-structured interviews were conducted with parents of critically ill infants admitted to neonatal intensive care and prospectively enrolled in a study of communication in critical care decision making. Interviews were transcribed verbatim and uploaded into NVivo V.10 to manage and facilitate data analysis. Thematic analysis identified themes representing the data.ResultsNineteen interviews conducted with 14 families identified 4 themes: (1) initial impact of admission affecting transition into the neonatal unit; (2) impact of consistency of care, care givers and information giving; (3) impact of communication in facilitating or hindering parental autonomy, trust, parental expectations and interactions; (4) parental perception of respect and humane touches on the neonatal unit.ConclusionFactors including the context of infant admission, interprofessional consistency, humane touches of staff and the transition into the culture of the neonatal unit are important issues for parents. These issues warrant further investigation to facilitate individualised family needs, attachment between parents and their baby and the professional team.
Mode of delivery and outcomes of infants with gastroschisis: a meta-analysis of observational studies
Authors: Kirollos Dina W , Abdel-Latif Mohamed E 
Published: October 2017

BackgroundThere is controversy among the literature for electing caesarean section (CS) delivery for infants with gastroschisis in an attempt to reduce mortality and morbidity.ObjectiveThis meta-analysis investigates whether there is enough evidence to support CS delivery over vaginal delivery.Data sourcesWe conducted our search in April 2017. We searched Cochrane, Medline, Premedline, Embase, CINAHL, GoogleScholar and Web of Science. We also searched conferences for abstracts online. Additional studies were retrieved by reviewing reference lists.Study selectionObservational studies, excluding case series, were eligible if data compared relevant outcomes of infants with gastroschisis in relation to mode of delivery.Data extractionRelevant information were extracted and assessed the methodological quality of the retrieved records.ResultsThirty-eight studies were included. Evidence suggested that mode of delivery is not significantly associated with overall mortality (OR 0.82, 95% CI 0.57 to 1.18), primary repair (OR 0.82, 95% CI 0.57 to 1.18), neonatal mortality (OR 1.08, 95% CI 0.54 to 2.15), necrotising enterocolitis, secondary repair, sepsis, short gut syndrome, duration until enteral feeding and duration of hospital stay. Furthermore, sensitivity analyses based on economic status and quality of study showed no significant difference between the impact of mode of delivery for all investigated outcomes.LimitationsDue to uncontrolled variables between and within studies, particularly regarding characteristics of delivery and postdelivery care, it is difficult to extract meaningful results from the literature.ConclusionsThere is insufficient evidence to advocate the use of CS over vaginal delivery for infants with gastroschisis.
Respiratory adaptation in term infants following elective caesarean section
Authors: Finn Daragh , De Meulemeester Julie , Dann Lisa , Herlihy Ita , Livingstone Vicki , Boylan Geraldine B , Ryan C Anthony , Dempsey Eugene M 
Published: October 2017

ObjectiveTo determine respiratory rate (RR), tidal volume (TV) and end-tidal carbon dioxide (EtCO2) values in full-term infants immediately after caesarean section, and to assess whether infants that develop transient tachypnoea of the newborn (TTN) follow the same physiological patterns.Design and patientsA Respironics NM3 Monitor (Philips, Netherlands) continuously measured RR, TV and EtCO2 for 7 min in infants >37 weeks’ gestation following elective caesarean section (ECS). Monitoring was repeated at 2 hours of age for 2 min. Gestation, birth weight, Apgar scores and admissions to neonatal unit were documented.SettingThe operative delivery theatre of Cork University Maternity Hospital, Ireland.ResultsThere were 95 term infants born by ECS included. Median (IQR) gestation was 39 weeks (38.2–39.1) and median (IQR) birth weight 3420 g (3155–3740). Median age at initiation of monitoring was 26.5 s (range: 20–39). Data were analysed for the first 7 min of life. Mean breaths per minute (bpm) increased over the first 7 min of life (44.31–61.62). TV and EtCO2 values were correlated and increased from 1 min until maximum mean values were recorded at 3 min after delivery (5.18 mL/kg–6.44 mL/kg, and 4.32 kPa–5.64 kPa, respectively). Infants admitted to the neonatal unit with TTN had significantly lower RRs from 2 min of age compared with infants not admitted for TTN.ConclusionsTV and EtCO2 values are correlated and increase significantly over the first few minutes following ECS. RR increases gradually from birth, and rates were lower in infants that develop TTN.
Nasal injury in preterm infants receiving non-invasive respiratory support: a systematic review
Authors: Imbulana Dilini I , Manley Brett J , Dawson Jennifer A , Davis Peter G , Owen Louise S 
Published: October 2017

ObjectiveBinasal prongs are the most commonly used interface for the delivery of nasal positive airway pressure (CPAP) to preterm infants. However, they are associated with pressure-related nasal injury, which causes pain and discomfort. Nasal injury may necessitate a change in interface and occasionally damage is severe enough to require surgical repair. We aim to determine the incidence and risk factors for nasal injury in preterm infants, and to provide clinicians with strategies to effectively prevent and treat it.DesignWe conducted a systematic search of databases including MEDLINE (PubMed including the Cochrane Library), EMBASE, CINAHL and Scopus. Included studies enrolled human preterm infants and were published prior to 20 February 2017.ResultsForty-five studies were identified, including 14 ra ndomised controlled trials, 10 observational studies, two cohort studies, eight case reports and 11 reviews. The incidence of nasal injury in preterm infants ranged from 20–100%. Infants born <30 weeks’ gestation are at highest risk. Strategies shown to reduce nasal injury included: nasal barrier dressings (2 studies, n=244, risk ratio (RD) −0.12, 95%, CI − 0.20 to −0.04), nasal high flow therapy as an alternative to binasal prong CPAP (7 studies, n=1570, risk difference (RD) −0.14, 95% CI −0.17 to −0.10), and nasal masks rather than binasal prongs (5 studies, n=544, RR 0.80, 95% CI 0.64 to 1.00).Conclusions and relevanceNasal injury is common in preterm infants born <30 weeks’ gestational age receiving CPAP via binasal prongs. Larger randomised trials are required to fully evaluate strategies to reduce nasal injury.
Differences in clinical ocular outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix: a systematic review of published literature
Authors: Ramírez Soto Max Carlos 
Published: October 2017

BackgroundSporotrichosis is an implantation mycosis caused by Sporothrix species prevalent worldwide, which occasionally can also result in intraocular infection presenting as an exogenous or endogenous infection (disseminated sporotrichosis). Knowledge in its clinical recognition and management is limited.AimsTo systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix.MethodsCase reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups.ResultsFrom 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration.ConclusionsAnterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas. Sporothrix infection should be included in the differential diagnosis for ocular inflammation, regardless of the presence or absence of autoimmune comorbidities and whether the patient resides in an endemic area or not. Ophthalmologists should consider intravitreal and systemic antifungal therapy for exogenous and endogenous endophthalmitis caused by Sporothrix.
Risk factors for extraophthalmic involvement and treatment outcomes in patients with IgG4-related ophthalmic disease
Authors: Park Jinku , Lee Min Joung , Kim Namju , Kim Ji Eun , Park Sun-Won , Choung Ho-Kyung , Khwarg Sang In 
Published: October 2017

Background/aimTo analyse the clinical risk factors for extraophthalmic involvement and treatment outcomes in patients with IgG4-related ophthalmic disease (IgG4-ROD) in Korea.MethodsWe retrospectively reviewed medical records of 42 patients diagnosed with IgG4-ROD confirmed by a surgical biopsy during the 7-year period, between January 2009 and March 2015, at three tertiary referral centres in Korea. Data regarding patients’ demographics, clinical characteristics and radiological findings were obtained. The relapse rate was compared between systemic steroids only and combined immunosuppressant therapy.ResultsThe mean patient age was 55.2 years (male:female ratio, 1:1). Based on the primary orbital structure affected, the IgG4-RODs were classified as dacryoadenitis (52.4%), orbital soft tissue inflammation (21.4%), trigeminal nerve involvement (11.9%) and myositis (9.5%). Extraophthalmic involvement (n=21) was associated with bilateral involvement (p=0.004), longer symptom duration (p=0.033) and a higher serum IgG4 level (p=0.034). Initial treatment regimens included attentive observation (n=7), prednisolone alone (n=22) and prednisolone plus immunosuppressive agent (n=13). During follow-up (mean, 24 months), 13 patients (37.1%) experienced relapse. In the extraophthalmic involvement group, steroid therapy alone resulted in a significantly higher relapse rate than combined immunosuppressant treatment (p=0.028).ConclusionBilateral involvement, longer symptom duration and higher IgG4 levels were significant risk factors for extraophthalmic involvement in Korean patients with IgG4-ROD. In patients with an extraophthalmic involvement, prednisolone combined with an immunosuppressive agent was more effective for preventing recurrence than prednisolone alone.
Tolerable rates of visual field progression in a population-based sample of patients with glaucoma
Authors: Salonikiou Angeliki , Founti Panayiota , Kilintzis Vassilis , Antoniadis Antonis , Anastasopoulos Eleftherios , Pappas Theofanis , Raptou Anastasia , Topouzis Fotis 
Published: October 2017

AimsTo provide population-based data on the maximum tolerable rate of progression to avoid visual impairment (maxTRoP_VI) and blindness (maxTRoP_BL) from open-angle glaucoma (OAG).MethodsParticipants with OAG in the Thessaloniki Eye Study (cross-sectional, population-based study in a European population) were included in the analysis. Visual impairment was defined as mean deviation (MD) equal to or worse than −12dB and blindness as MD equal to or worse than −24dB. Additional thresholds for visual impairment were tested. For each participant maxTRoP_VI was defined as the rate of progression which would not lead to visual impairment during expected lifetime. MaxTRoP_BL was defined accordingly. Both parameters were calculated for each OAG subject using age, sex, MD and life expectancy data. The eye with the better MD per subject was included in the analysis.ResultsAmong 135 subjects with OAG, 123 had reliable visual fields and were included in the analysis. The mean age was 73±6 years and the median MD was −3.65±5.28dB. Among those, 69.1% would have a maxTRoP_VI slower than −1dB/year and 18.7% would have a maxTRoP_VI between −1 and −2dB/year. Also, 72.4% would have a maxTRoP_BL slower than −2dB/year. For all tested thresholds for visual impairment, approximately 86% of the OAG study participants would not be able to tolerate a rate of progression equal to or faster than −2dB/year.ConclusionsThe majority of patients with glaucoma in our study would have a maximum tolerable rate of progression slower than −1dB/year in their better eye. Patient-tailored strategies to monitor the visual field are important, but raise the issue of feasibility with regard to the number of visual field tests needed.