bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Genotypes of Adhesion Operon Genes in Staphylococcus epidermidis Isolates From Various Ocular Infections
Authors: Sharifinejad Mehrnoush , Shokatpour Narjes , Farnaghi Farshad , Abedinyfar Zohreh , Amoli Fahimeh Asadi , Doustdar Farahnoosh
Published: December 2017

Background:

Staphylococcus epidermidis is one of the common causes of bacterial keratitis and post-operation infections. One of the most important virulence factors of S. epidermidis is biofilm formation. Poly-N-acetylglucosamine (PNAG) production is critical for biofilm formation in S. epidermidis. The intercellular adhesion (ica) operon is formed by icaA, icaD, icaB, and icaC genes, which participate in the biosynthesis of PNAG. Strains of S. epidermidis from different infections show different genotypes in relation to adhesion operon genes. Therefore, regarding the fact that the pathogenic strain in each community has unique genotypes, this study investigated the relation between ica operon genotypes and various ocular infections. However, the correlation between the ica operon genes and the mecA gene was analyzed in the isolates.

Methods:

For this study, samples of the conjunctiva, cornea, and intraocular fluid of patients with ocular infection were collected. After culture and incubation, detection of S. epidermidis was performed using biochemical and coagulase tests. The antibiotic susceptibility of the bacteria was evaluated by the disk diffusion method. After this, DNA was extracted from the bacteria and the presence of icaA, icaD, is256, and mecA genes was analyzed using polymerase chain reaction.

Results:

All 50 coagulase-negative Staphylococcus samples isolated from different eye infections were characterized as S. epidermidis. Most of the samples (36%) were isolated from the cornea and the others were, respectively, from the conjunctiva (24%), vitreous (20%), anterior chamber (8%), eyelid (6%), and nasolacrimal duct (6%). The icaA, icaD, and is256 genes were detected with different genotypes in isolates from keratitis and endophthalmities compared with conjunctivitis. Overall, the most isolated genotype from ocular infections was icaA+. icaD+. is256+. (46%). Most of the isolates (82.60%) had mecA, icaA, and icaD genes simultaneously, which indicates a strong relationship between the adhesion genes and the antibiotic resistance gene.

Conclusions:

The adhesion operon genes were observed with different genotypes in S. epidermidis samples isolated from various ocular infections.
The Epidemiology of Healthcare-associated Infections in Pediatric Cardiac Intensive Care Units
Authors: Alten Jeffrey A. , Rahman A. K. M. Fazlur , Zaccagni Hayden J. , Shin Andrew , Cooper David S. , Blinder Joshua J. , Retzloff Lauren , Aban Inmaculada B. , Graham Eric M. , Zampi Jeffrey , Domnina Yuliya , Gaies Michael G.
Published: December 2017

Background:

Healthcare-associated infections (HAIs) represent serious complications for patients within pediatric cardiac intensive care units (CICU). HAIs are associated with increased morbidity, mortality and resource utilization. There are few studies describing the epidemiology of HAIs across the entire spectrum of patients (surgical and nonsurgical) receiving care in dedicated pediatric CICUs.

Methods:

Retrospective analyses of 22,839 CICU encounters from October 2013 to September 2016 across 22 North American CICUs contributing data to the Pediatric Cardiac Critical Care Consortium clinical registry.

Results:

HAIs occurred in 2.4% of CICU encounters at a rate of 3.3 HAIs/1000 CICU days, with 73% of HAIs occurring in children <1 year. Eighty encounters (14%) had ≥2 HAIs. Aggregate rates for the 4 primary HAIs are as follows: central line–associated blood stream infection, 1.1/1000 line days; catheter-associated urinary tract infections, 1.5/1000 catheter days; ventilator-associated pneumonia, 1.9/1000 ventilator days; surgical site infections, 0.81/100 operations. Surgical and nonsurgical patients had similar HAIs rates/1000 CICU days. Incidence was twice as high in surgical encounters and increased with surgical complexity; postoperative infection occurred in 2.8% of encounters. Prematurity, younger age, presence of congenital anomaly, Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT) 4–5 surgery, admission with an active medical condition, open sternum and extracorporeal membrane oxygenation were independently associated with HAIs. In univariable analysis, HAI was associated with longer hospital length of stay and durations of urinary catheter, central venous catheter and ventilation. Mortality was 24.4% in patients with HAIs versus 3.4% in those without, P < 0.0001.

Conclusions:

We provide comprehensive multicenter benchmark data regarding rates of HAIs within dedicated pediatric CICUs. We confirm that although rare, HAIs of all types are associated with significant resource utilization and mortality.
Visceral Leishmaniasis—Optimum Treatment Options in Children
Authors: Sundar Shyam , Agarwal Dipti
Published: December 2017

Visceral leishmaniasis affects 200–400 thousands people annually worldwide. For last few decades, there has been a steady decline in the response to pentavalent antimonial (Sbv), the drug that has been used for treating visceral leishmaniasis for almost a century. Oral miltefosine and amphotericin B are alternative drugs being been used in the treatment of leishmaniasis in children. Liposomal amphotericin B has the advantage over conventional amphotericin B is that higher doses can be given with fewer adverse effects. Liposomal amphotericin B in combination with other drugs is the preferred treatment option globally especially in Indian subcontinent. Combination therapy with multiple drugs should undergo larger clinical trials in children as these will shorten the duration of therapy, improve compliance and decrease both toxicity and drug resistance.
Impact of steatosis and inflammation definitions on the performance of NASH tests
Authors: Poynard Thierry , Munteanu Mona , Charlotte Frederic , Perazzo Hugo , Ngo Yen , Deckmyn Olivier , Pais Raluca , Mathurin Philippe , Ratziu Vlad
Published: December 2017

Background and aim

One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the limitations of similar European (Fatty Liver Inhibition of Progression) and USA (Clinical-Research-Network) standard definitions and their impact on the construction of tests.

Methods

We hypothesized that a simpler histological definition of non-alcoholo steato-hepatitis (NASH), which does not require the presence of steatosis and the presence of both lobular inflammation and ballooning, should improve the concordance rates with previously validated blood tests. We reviewed the landmark studies in metabolic liver disease, sources of the standard definitions, and we compared the adequacy of these standards to other possible definitions in 1081 subjects with biopsies, by concordance and accuracy rates.

Results

The limitations of standard definitions included the presence of appropriate controls in only 6.6% of landmark studies, an arbitrary definition of steatosis and NASH covering only four (15%) out of 27 possible combinations of features, compared with 18 (67%) for a simplified NASH definition, which did not require steatosis. A total of 39/1081 (3.6%) cases were not identified by standard definition, but were identified by the simplified definition as significant active disease, including 15 cases with significant fibrosis. The simplified definition increased the κ concordance (P<0.0001) between test prediction and histological reference.

Conclusion

A simplified definition of NASH could help in the construction of biomarkers with higher performances.
New therapeutic strategies for high-risk acute myeloid leukemia
Authors: Menghrajani Kamal , Tallman Martin S.
Published: December 2017

Purpose of review

Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease.

Recent findings

Induction therapy is in the process of changing for several patient populations. The introduction of CPX-351 offers a novel strategy for treating patients with therapy-related AML or AML with myelodysplasia-related changes; gemtuzumab ozogamicin may become incorporated into standard induction therapy, especially for patients with core-binding factor leukemias; and for older adults, combination therapy with venetoclax may offer a more efficacious strategy than the single-agent regimens previously used. Additionally, targeted therapies are now becoming available for patients with mutations in FMS-like tyrosine kinase 3 (FLT3) or isocitrate dehydrogenase 2 (IDH2), ushering in an era of personalized medicine in the treatment of AML.

The US Food and Drug Administration approval of several agents in 2017 will change the way AML treatment is approached and will offer both clinicians and patients a new armamentarium with which to treat this disease.
When should patients receive consolidation chemotherapy before allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission?
Authors: Yeshurun Moshe , Wolach Ofir
Published: December 2017

Purpose of review

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT.

Recent findings

Randomized controlled studies are lacking. Data derive largely from four large retrospective registry studies. These analyses are consistent in demonstrating the lack of any survival benefit for pretransplant consolidation chemotherapy once a patient achieves a complete remission and a donor is readily available. These results are valid across conditioning regimen intensities, donor sources, and doses of cytarabine administered during consolidation.

Available evidence suggests that patients with acute myeloid leukemia in first complete remission for whom a suitable donor is readily available should not be given pretransplant consolidation before proceeding to alloHCT, regardless of conditioning regimen intensity and that transplantation should be offered promptly at the time remission is achieved without undue delay. Nevertheless, patients for whom a suitable donor is not readily available after achieving first remission, should probably receive ‘bridging’ consolidation chemotherapy while waiting for a donor to be identified in an attempt to decrease the risk of early disease recurrence before transplantation. The role of minimal residual disease and genetic markers in directing consolidation choices are unclear to date.
Have haploidentical transplants replaced umbilical cord transplants for acute leukemias?
Authors: Liu Jia Hau , Kanakry Christopher G. , Luznik Leo
Published: December 2017

Purpose of review

Haploidentical stem cell transplantation (Haplo SCT) and umbilical cord blood stem cell transplantation (UCB SCT) have emerged over the past two to three decades as viable sources of alternative donor SCT when a human leukocyte antigen matched donor is not available. However, which of these two donor types is optimal for patients with leukemia in need of allografting is unknown.

Recent findings

For patients with acute leukemia, results of UCB SCT have been improved by the use of double umbilical cord units and emerging ex-vivo expansion technologies. However, the costs associated with procuring double cord units and high transplant-related mortality due to delayed immunological reconstitution and infections, particularly in adult patients, remain a problem. Recently, Haplo SCT has become an increasingly utilized alternative donor source. While improvements of ex-vivo T-cell depletion platforms continue, emergence of T-cell-replete platforms, such as the use of post-transplantation cyclophosphamide (PTCy), is increasingly being utilized in treating acute leukemia patients. PTCy-based Haplo SCT is gaining popularity among transplant clinicians due to its relatively easy learning curve, low cost, low incidence of graft-versus-host disease, and favorable survival in acute leukemia patients.

The clinical question of whether Haplo SCT should replace UCB SCT needs to be answered by ongoing randomized trials. However, the rapidly increasing adoption of Haplo SCT worldwide as the viable alternative for patients without a human leukocyte antigen-matched donor has seemingly addressed the question ahead of scientific judgment.
Sexual Networks of Racially Diverse Young MSM Differ in Racial Homophily But Not Concurrency
Authors: Janulis Patrick , Phillips Gregory , Birkett Michelle , Mustanski Brian
Published: December 2017

Background:

Substantial racial disparities exist in HIV infection among young men who have sex with men (YMSM). However, evidence suggests black YMSM do not engage in greater levels of risk behavior. Sexual networks may help explain this paradox. This study used egocentric exponential random graph models to examine variation in concurrency (ie, 2 or more simultaneous partners) and homophily (ie, same race/ethnicity partners) across race/ethnicity groups in a diverse sample of YMSM.

Methods:

Data for this study come from a longitudinal cohort study of YMSM. Participants (n = 1012) provided data regarding their sexual contacts during the 6 months before their first study visit. A series of egocentric exponential random graph models examined how providing separate estimates for homophily and concurrency parameters across race/ethnicity improved the fit of these models. Networks were simulated using these parameters to examine how local network characteristics impact risk at the whole network level.

Results:

Results indicated that homophily, but not concurrency, varied across race/ethnicity. Black participants witnessed significantly higher race/ethnicity homophily compared with white and Latino peers. Extrapolating from these models, black individuals were more likely to be in a connected component with an HIV-positive individual and closer to HIV-positive individuals. However, white individuals were more likely to be in large connected components.

Conclusions:

These findings suggest that high racial homophily combined with existing disparities in HIV help perpetuate the spread of HIV among black YMSM. Nonetheless, additional work is required to understand these disparities given that homophily alone cannot sustain them indefinitely.
Is there still a role for vancomycin in skin and soft-tissue infections?
Authors: Savoldi Alessia , Azzini Anna M. , Baur David , Tacconelli Evelina
Published: December 2017

Purpose of review

Skin and soft-tissue infections (SSIs) are among the commonest infections encountered in clinical practice. Spread of methicillin-resistant Staphylococcus aureus SSIs continues to increase in both health care and community settings and presents a challenge for the best treatment choice. Vancomycin has been the mainstay of SSIs treatment, but recently its use has been questioned because of concerns about its efficacy, tolerability, and unfavorable pharmacokinetic/pharmacodynamic profile. The purpose of this review is to establish the current role for vancomycin in light of the literature published from January 2007 to September 2017 on comparison with both old and new alternatives.

Recent findings

Meta-analyses show better clinical and microbiological outcomes for drugs approved for the treatment of SSI, including those sustained by methicillin-resistant S. aureus, in the last 10 years than for vancomycin. The newer glycopeptides and linezolid decrease the total treatment costs compared with vancomycin, by reducing the length of stay or avoiding the hospitalization.

Vancomycin is noninferior in efficacy and safety to all comparator drugs, including the newest on the market. However, the SSI treatment evidence base presents several shortcomings limiting the clinical applicability of the results. High-level clinical trials should be performed to obtain results that can be generalized and applied effectively in clinical practice.
A Quality Improvement Initiative to Reduce “Out-of-ICU” Cardiopulmonary Arrests in a Tertiary Care Hospital in India: A 2-Year Learning Experience
Authors: Menon Vidya P. , Prasanna Preetha , Edathadathil Fabia , Balachandran Sabarish , Moni Merlin , Sathyapalan Dipu , Pai Rajesh D. , Singh Sanjeev
Published: December 2017

Quality Problem or Issue:

To assess impact of medical emergency team (MET) in reducing “out-of-ICU” cardiopulmonary arrests and identify barriers to its optimal utilization.

Initial Assessment:

Frequently observed critical clinical signs and laboratory values of “out-of-ICU” crashes were used to develop Amrita Early Warning Criteria.

Choice of Solution:

A physician-led MET was established to respond to code MET, activated by a primary nurse.

Implementation:

Rates of “out-of-ICU” cardiopulmonary arrests per 1000 admissions were compared in pre-MET (2013-2014) and post-MET periods (2014-2016) along with disposition following MET and mortality. Descriptive statistics and logistic regression were used for comparative analysis.

Evaluation:

For continued quality improvement, a Likert agreement scale questionnaire collated the nurse's feedback on MET. 386 Code MET were recorded with an activation rate of 18.8 per 1000 inpatients for 2014-2016. Common MET triggers were desaturation (53%), seizure (10%), and syncope (9%). Seventy-one percent of activations were attended within 5 minutes, with 45% reported during nurse's night shift hours. Medical emergency team interventions resulted in 59% being shifted to ICU. In the “post-MET” period, “Cold Blue” dose reduced from 6.9 in 2013-2014 to 2.6 (P = .0002) in 2014-2015 and 3.2 (P = .01) in 2015-2016. Ninety-three percent of the Code Blues with prior MET calls were “delayed MET” and 28% of the Code Blues without prior MET activation were “missed MET.” Nurse's feedback revealed that 46% lacked knowledge of correct MET activation process while 31% expressed a fear of reprisal for inappropriate activation.

Lessons Learned:

Although MET intervention was successful in significantly reducing “out-of-ICU” Code Blues, focused training of nurses is required for continued quality improvement.
Thrombin Provokes Degranulation of Platelet α-Granules Leading to the Release of Active Plasminogen Activator Inhibitor-1 (PAI-1)
Authors: Huebner Benjamin R. , Moore Ernest E. , Moore Hunter B. , Stettler Gregory R. , Nunns Geoffrey R. , Lawson Peter , Sauaia Angela , Kelher Marguerite , Banerjee Anirban , Silliman Christopher C.
Published: December 2017

Background:

The balance of fibrinolytic mediators is crucial to the survival of the critically ill patient, with tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) playing significant roles. While elevated levels of PAI-1 are associated with increased morbidity and mortality, the source of this PAI-1 remains elusive. Platelets contain 90% of circulating plasma PAI-1, however, their ability to release active PAI-1 is controversial. We hypothesize platelets contain active PAI-1 in α-granules capable of immediate degranulation when exposed to high concentrations of thrombin.

Methods:

In vitro apheresis platelets were stimulated with thrombin (1 IU/mL, 5 IU/mL) followed by the collection of supernatant (5–120 min). Supernatant and lysate PAI-1 was measured by ELISA. The experiment was repeated in the presence of t-PA followed by measurement of t-PA:PAI-1 complex measurement by ELISA. Finally, healthy whole blood underwent dilution with control and thrombin-treated platelet lysate followed by thrombelastography (TEG) in a t-PA-stimulated TEG.

Results:

Thrombin provoked immediate near-complete degranulation of PAI-1 from α-granules (median 5m 5 IU/mL thrombin 125.1 ng/mL, 1 IU/mL thrombin 114.9 ng/mL, control 9.9 ng/mL). The released PAI-1 rapidly complexed with t-PA, with a 4-fold increase in complex formation in the thrombin-treated supernatant. Conversely, PAI-1 in the control lysate demonstrated a 6-fold increase in complex formation compared with thrombin lysate. Last, control platelet lysate inhibited t-PA-induced fibrinolysis by TEG (median LY30 control 15m 7.9%), while thrombin-treated platelet lysates, after PAI-1 degranulation, were unable to affect the fibrinolysis profile (median LY30 5 IU/mL 28.5%, 1 IU/mL 12.4%).

Conclusion:

Thrombin provokes rapid α-degranulation of active PAI-1, capable of complexing with t-PA and neutralizing t-PA-induced fibrinolysis by TEG.
Critical Illness-Related Corticosteroid Insufficiency in Cardiogenic Shock Patients: Prevalence and Prognostic Role
Authors: Ducrocq Nicolas , Biferi Pascal , Girerd Nicolas , Latar Ichraq , Lemoine Simon , Perez Pierre , Thivilier Carine , Levy Bruno , Kimmoun Antoine
Published: December 2017

Background:

Cardiogenic shock shares with septic shock common hemodynamic features, inflammatory patterns, and most likely similar complications such as critical illness-related corticosteroid insufficiency. The aim of this study was to evaluate the prevalence of critical illness-related corticosteroid insufficiency in cardiogenic shock patients and to secondarily assess its prognostic value on 90-day mortality.

Methods:

A single-center prospective observational study conducted over a 3-year period and including all patients with cardiogenic shock. Main exclusion criteria were patients with prior cardiac arrest, sepsis, ongoing corticosteroid therapy, and etomidate administration. A short corticotropin test was performed in the first 24 h following admission. Serum cortisol levels were measured before (T0) and 60 min (T60) after administration of 250 μg of cosyntropin. Critical illness-related corticosteroid insufficiency was defined according to the 2017 consensus definition (basal total cortisol<10 μg·dL−1 or a delta cortisol T60-T0<9 μg·dL−1) as well as the thresholds published in 2016 in cardiogenic shock patients associated with worst prognosis (basal total cortisol>29 μg·dL−1 and delta cortisol T60-T0<17 μg·dL−1).

Results:

Seventy-nine consecutive patients hospitalized in intensive care for cardiogenic shock met the inclusion criteria. Overall mortality was 43% at day 90. Forty-two percent had critical illness-related corticosteroid insufficiency using the 2017 consensus definition and 32% using the 2016 cardiogenic shock thresholds. Presence of critical illness-related corticosteroid insufficiency was not an independent factor associated with 90-day mortality irrespective of the thresholds used.

Conclusion:

Critical illness-related corticosteroid insufficiency is a frequent occurrence in medical cardiogenic shock. However, in this study, such insufficiency was not associated with prognosis.
Hydrogen Inhalation is Superior to Mild Hypothermia for Improving Neurological Outcome and Survival in a Cardiac Arrest Model of Spontaneously Hypertensive Rat
Authors: Chen Gang , Chen Bihua , Dai Chenxi , Wang Jianjie , Wang Juan , Huang Yuanyuan , Li Yongqin
Published: December 2017

Background:

Postcardiac arrest syndrome is the consequence of whole-body ischemia–reperfusion events that lead to multiple organ failure and eventually to death. Recent animal studies demonstrated that inhalation of hydrogen greatly mitigates postresuscitation myocardial dysfunction and brain injury. However, the influence of underlying heart disease on the efficacy of hydrogen is still unknown. In the present study, we investigated the effects of hydrogen inhalation on neurological outcome and survival in a cardiac arrest model of spontaneously hypertensive rat (SHR).

Methods:

Cardiopulmonary resuscitation was initiated after 4 min of untreated ventricular fibrillation in 40 SHRs. Immediately after successful resuscitation, animals were randomized to be ventilated with 98% oxygen and 2% nitrogen under normothermia (Ctrl), 2% nitrogen under hypothermia (TH), 2% hydrogen under normothermia (H2), or 2% hydrogen under hypothermia (H2+TH) for 2 h. Hypothermia was maintained at 33°C for 2 h. Animals were observed up to 96 h for assessment of survival and neurologic recovery.

Results:

No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Compared with Ctrl, serum cardiac troponin T measured at 5 h and myocardial damage score measured at 96 h after resuscitation were markedly reduced in H2, TH, and H2+TH groups. Compared with Ctrl and TH, astroglial protein S100 beta measured during the earlier postresuscitation period, and neurological deficit score and neuronal damage score measured at 96 h were considerably lower in both H2 and H2+TH groups. Ninety-six hours survival rates were significantly higher in the H2 (80.0%) and H2+TH (90.0%) groups than TH (30.0%) and to Ctrl (30.0%).

Conclusions:

Hydrogen inhaling was superior to mild hypothermia for improving neurological outcome and survival in cardiac arrest and resuscitation model of systemic hypertension rats.
Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Holland Michael A. , Joyce John S. , Brennaman Lisa M. , Drobnis Erma Z. , Starr Julie A. , Foster Raymond T.
Published: December 2017

Objectives

Pelvic floor hypertonic disorder is characterized by an involuntary spasm of the levator ani muscles and is associated with several clinical syndromes. Several treatment options have been described; however, treatment efficacy data are limited. The objective of this study was to determine the efficacy of intravaginal diazepam for the treatment of pelvic pain secondary to levator ani muscle spasm in comparison to placebo.

Methods

Adult women with complaints of pelvic pain, who were noted to have levator ani muscle spasm on physical examination, were approached for enrollment in a double-blind, placebo-controlled, randomized clinical trial. Eligible participants were randomized to receive 10-mg diazepam capsules or identical-appearing placebo capsules. The primary outcome was the change in pain scores measured by a 100-mm visual analog scale at 4 weeks. Several validated questionnaires were similarly assessed as secondary outcomes.

Results

In total, 49 women were randomized (25 in the diazepam arm and 24 in the placebo arm). At 4 weeks, 35 women returned for follow-up and had complete data available analysis. There was no difference in visual analog scale scores between the treatment groups after 4 weeks (50 vs 39 mm, for diazepam and placebo, respectively; P = 0.36). There were also no differences noted in the questionnaire scores.

Conclusions

It is unlikely that self-administered intravaginal diazepam suppositories promote an improvement in the 100-mm visual analog scale of 20 mm or more or other substantial symptom improvement in women with pelvic floor hypertonic disorder.
A Near Complete Zonal Map of Mouse Olfactory Receptors
Authors: Tan Longzhi , Xie X. Sunney
Published: December 2017

In the mouse olfactory system, spatially regulated expression of > 1,000 olfactory receptors (ORs) ― a phenomenon termed “zones” ― forms a topological map in the main olfactory epithelium (MOE). However, the zones of most ORs are currently unknown. By sequencing mRNA of 12 isolated MOE pieces, we mapped out zonal information for 1,033 OR genes with an estimated accuracy of 0.3 zones, covering 81% of all intact OR genes and 99.4% of total OR mRNA abundance. Zones tend to vary gradually along chromosomes. We further identified putative non-OR genes that may exhibit zonal expression.
A cloning-free method for CRISPR/Cas9-mediated genome editing in fission yeast
Authors: Zhang Xiao-Ran , He Jia-Bei , Wang Yi-Zheng , Du Li-Lin
Published: December 2017

The CRISPR/Cas9 system, which relies on RNA-guided DNA cleavage to induce site-specific DNA double-strand breaks, is a powerful tool for genome editing. This system has been successfully adapted for the fission yeast Schizosaccharomyces pombe by expressing Cas9 and the single-guide RNA (sgRNA) from a plasmid. In the procedures published to date, the cloning step that introduces a specific sgRNA target sequence into the plasmid is the most tedious and time-consuming. To increase the efficiency of applying the CRISPR/Cas9 system in fission yeast, we here developed a cloning-free procedure that uses gap repair in fission yeast cells to assemble two linear DNA fragments, a gapped Cas9-encoding plasmid and a PCR-amplified sgRNA insert, into a circular plasmid. Both fragments contain only a portion of the ura4 or bsdMX marker so that only the correctly assembled plasmid can confer uracil prototrophy or blasticidin resistance. We show that this gap-repair-based and cloning-free CRISPR/Cas9 procedure permits rapid and efficient point mutation knock-in, endogenous N-terminal tagging, and genomic sequence deletion in fission yeast.
Genetic structure of the grey side-gilled sea slug (Pleurobranchaea maculata) in coastal waters of New Zealand
Authors: Yıldırım Yeşerin , Anderson Marti J. , Patel Selina , Millar Craig D. , Rainey Paul B.
Published: December 2017

Pleurobranchaea maculatais a rarely studied species of the Heterobranchia found throughout the south and western Pacific – and recently recorded in Argentina – whose population genetic structure is unknown. Interest in the species was sparked in New Zealand following a series of dog deaths caused by ingestions of slugs containing high levels of the neurotoxin tetrodotoxin. Here we describe the genetic structure and demographic history ofP. maculatapopulations from five principle locations in New Zealand based on extensive analyses of 12 microsatellite loci and theCOIandCytBregions of mitochondrial DNA (mtDNA). Microsatellite data showed significant differentiation between northern and southern populations with population structure being associated with previously described regional variations in tetrodotoxin concentrations. However, mtDNA sequence data did not support such structure, revealing a star-shaped haplotype network with estimates of expansion time suggesting a population expansion in the Pleistocene era. Inclusion of publicly available mtDNA sequence from Argentinian sea slugs did not alter the star-shaped network. We interpret our data as indicative of a single founding population that fragmented following geographical changes that brought about the present day north-south divide in New Zealand waters. Lack of evidence of cryptic species supports data indicating that differences in toxicity of individuals among regions are a consequence of differences in diet.
Toward fast and accurate SNP genotyping from whole genome sequencing data for bedside diagnostics
Authors: Sun Chen , Medvedev Paul
Published: December 2017

Motivation

Genotyping a set of variants from a database is an important step for identifying known genetic traits and disease related variants within an individual. The growing size of variant databases as well as the high depth of sequencing data pose an efficiency challenge. In clinical applications, where time is crucial, alignment-based methods are often not fast enough. To fill the gap, Shajii et al. (2016) propose LAVA, an alignment-free genotyping method which is able to more quickly genotype SNPs; however, there remains large room for improvements in running time and accuracy.

Results

We present the VarGeno method for SNP genotyping from lllumina whole genome sequencing data. VarGeno builds upon LAVA by improving the speed of k-mer querying as well as the accuracy of the genotyping strategy. We evaluate VarGeno on several read datasets using different genotyping SNP lists. VarGeno performs 7-13 times faster than LAVA with similar memory usage, while improving accuracy.

Availability

VarGeno is freely available at: https://github.com/medvedevgroup/vargeno.
Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease
Authors: Meng Guofeng , Mei Hongkang
Published: December 2017

Background

The pathogenesis of Alzheimer’s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes.

Methods

Applying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.

Results

97 genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer’s disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the evolutionary conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles.

Conclusion

Overall, our study reveals a profile of transcriptional dysregulation in the genesis of Alzheimer’s disease by forming a core network with altered regulation; the core network is associated with Alzheimer’s diseases by affecting the aging and synaptic functions related genes; the gene regulation in brain may not be conservative between human and mouse.
Elections and Subjective Living Conditions in Sub‐Saharan Africa
Authors: Zeydanli Tugba
Published: December 2017

In sub‐Saharan Africa (SSA), competitive elections can cause considerable violence and widespread destruction of property, most of which is ethnically motivated. Recent literature shows that ethnic identification is more prominent during competitive election periods in comparison to other identifying categories such as gender, religion, and class/occupation. This paper utilizes data from 12 SSA countries and over 40,000 respondents taken from the Afrobarometer. It asks if individual perceived living conditions changes in the run‐up to competitive elections. Strong evidence shows that a perceived living condition does change. It is positively related to the proximity to an election and this proximity effect depends on the competitiveness of the election. The paper further investigates the background mechanisms behind this positive relationship, that is, to what extent does living conditions of the individual change if the party that the individual supports wins the election and is there a change in living conditions of the individual before and after the election? In addition, this paper documents that ethnic identification also has a positive impact on individual perceived living conditions after controlling for electoral cycle variables.
Foreign Direct Investment in Ghana: The Role of Infrastructural Development and Natural Resources
Authors: Anarfo Ebenezer Bugri , Agoba Abel Mawuko , Abebreseh Robert
Published: December 2017

This paper examines the role of infrastructural development and natural resources on FDI inflows in Ghana. We examine the empirical relations using the Prais–Winsten regression estimation procedure which is meant to overcome autocorrelation and heteroscedasticity in the error terms in the model, often for regressions applied to series. The data was obtained from World Development Indicators (WDI) spanning from 1975 to 2014. Our findings suggest that infrastructural development and natural resources are drivers of FDI inflows in Ghana. The other variables that significantly influence FDI inflows in Ghana include the lending interest rate, market size and GDP growth rate. The policy implications of this study is that, while Ghana seeks to expand its infrastructure and natural resources to enhance FDI inflows and economic growth, this must be done in tandem with creating an enabling environment to ensure macroeconomic stability.
FDI Determinants in Least Recipient Regions: The Case of Sub‐Saharan Africa and MENA
Authors: Okafor Godwin , Piesse Jenifer , Webster Allan
Published: December 2017

This paper explores the determinants of foreign direct investment (FDI) into FDI least recipient regions. Panel data for 20 sub‐Saharan Africa (SSA) and 11 Middle East and North Africa (MENA) countries are used for the period 2000–12. Findings of the fixed effects estimations suggest that FDI inflows into these regions are influenced by GDP per capita, infrastructure development, trade openness, and control of corruption. Conversely, inflation negatively affects FDI inflows, and rents from natural resources do not significantly influence FDI. Furthermore, the findings show that marginal benefits from any increase in the quantity of FDI determinants (with the exception of control of corruption) will be less for SSA countries. The paper concludes with important policy implications deduced from the findings.
Multinationals and Skills Policy Networks: HRM as a Player in Economic and Social Concerns
Authors: Tregaskis Olga , Almond Phil
Published: December 2017

This paper uses an embeddedness framework to reconceptualize HRM agency over the external labour market, and in so doing bring into focus the societal implications of HRM. Drawing on qualitative data from 53 key informants in two English regions, we identify the ways in which the subsidiaries of foreign multinationals (MNCs) engage with labour market skills actors. Our findings reveal how power structures are mobilized by local economic actors to align labour market skills with MNCs’ demand priorities. We show that multinationals may seek to partially endogenize (i.e. take ownership of) the resources of local labour markets when their competitive value is redefined in social as well as economic terms, and demonstrate that the social structure of sub‐national institutional governance arrangements and firm strategic action on skills creates the conduit through which resource endogenization may occur. Theoretically, this paper identifies the social structure of networks as a casual mechanism to bridge divergent skill interests, which is mobilized when network actors have the capacity to frame fields within the social structure of the network around ideas on economic sustainability and moral interest.
‘Just because a doctor says something, doesn't mean that [it] will happen’: self‐perception as having a Fertility Problem among Infertility Patients
Authors: Leyser‐Whalen Ophra , Greil Arthur L. , McQuillan Julia , Johnson Katherine M. , Shrefffler Karina M.
Published: December 2017

Only some individuals who have the medically defined condition ‘infertility’ adopt a self‐definition as having a fertility problem, which has implications for social and behavioural responses, yet there is no clear consensus on why some people and not others adopt a medical label. We use interview data from 28 women and men who sought medical infertility treatment to understand variations in self‐identification. Results highlight the importance of identity disruption for understanding the dialectical relationship between medical contact and self‐identification, as well as how diagnosis acts both as a category and a process. Simultaneously integrating new medical knowledge from testing and treatment with previous fertility self‐perceptions created difficulty for settling on an infertility self‐perception. Four response categories emerged for adopting a self‐perception of having a fertility problem: (i) the non‐adopters – never adopting the self‐perception pre‐ or post‐medical contact; (ii) uncertain – not being fully committed to the self‐perception pre‐ or post‐medical contact; (iii) assuming the label – not having prior fertility concerns but adopting the self‐perception post‐medical contact; and (iv) solidifying a tentative identity – not being fully committed to a self‐perception pre‐medical contact, but fully committed post‐medical contact. (A virtual abstract of this paper can be viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA).
Irrigator relations with water in the Sunraysia region, northwestern Victoria
Authors: Head Lesley , Klocker Natascha , Dun Olivia , Spaven Tess
Published: December 2017

Irrigated agriculture faces significant challenges under climate change, and may not be feasible in parts of the Murray‐Darling Basin beyond 2050. Recent research into the cultural politics of water has paid limited attention to the water cultures and relations of irrigators in Minority World countries. We analyse the water relations of grape farm irrigators in the Sunraysia region of Victoria using interviews and farm tours undertaken between 2014 and 2016. Findings are summarised under five themes: (1) the sociality of irrigation water, (2) temporal and spatial relations, (3) the risk of rain, (4) the micro‐scale of water knowledge, and (5) environment as actor. These themes shed light on the diverse relations that constitute both environmental and irrigation water. Irrigators are embedded in these relations at multiple scales, local and distant, mediated by technology and infrastructure. The scale of our focus makes visible water and other forms of environmental knowledge that often go unnoticed in broader debates over irrigation. The concept of “the environment”, understood as an embodied actor in policy discourse and by irrigators, is an emergent trend that warrants ongoing research attention.
High dietary intake of branched‐chain amino acids is associated with an increased risk of insulin resistance in adults
Authors: Asghari Golaleh , Farhadnejad Hossein , Teymoori Farshad , Mirmiran Parvin , Tohidi Maryam , Azizi Fereidoun
Published: December 2017

Background

The aim of this study was to investigate the association between branched‐chain amino acid (BCAA) intake and markers of insulin metabolism in adults.

Methods

This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 1205 subjects, aged ≥20 years, who were followed‐up for a mean of 2.3 years. Dietary intake of BCAAs, including valine, leucine, and isoleucine, was determined using a valid and reliable food frequency questionnaire. Hyperinsulinemia, β‐cell dysfunction, insulin resistance (IR), and insulin insensitivity were determined according to optimal cut‐off values. Logistic regression was to estimate the occurrence of IR across tertiles of BCAA intake.

Results

The mean (± SD) age and BCAA intake of participants (43% male) at baseline were 42.7 ± 13.1 years and 13.8 ± 5.1 g/day, respectively. The incidence of hyperinsulinemia, β‐cell dysfunction, insulin insensitivity, and IR was 19.5%, 24.0%, 28.0%, and 12.5%, respectively. After adjustment for confounding variables, subjects in the highest tertile for total BCAAs (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.03–2.71), leucine (OR 1.75; 95% CI 1.09–2.82), and valine (OR 1.61; 95% CI 1.01–2.60) intake had a greater risk of incident IR than subjects in the lowest tertile. A higher intake of isoleucine was not associated with risk of incident IR. There was no association of total BCAAs, leucine, isoleucine, and valine intake with the risk of hyperinsulinemia, insulin insensitivity, or β‐cell dysfunction.

Conclusion

The findings of this study support the hypothesis that higher intakes of BCAAs may have adverse effects on the development of IR.
Sex hormones in alcohol consumption: a systematic review of evidence
Authors: Erol Almila , Ho Ada M.‐C. , Winham Stacey J. , Karpyak Victor M.
Published: December 2017

Sex hormones play an important role in establishing sex‐distinctive brain structural and functional variations that could contribute to the sex differences in alcohol consumption behavior. Here, we systematically reviewed articles that studied sex hormone impacts on alcohol consumption and alcohol use disorder (AUD). An extensive literature search conducted in MEDLINE, PubMed, Scopus and CINAHL databases identified 776 articles, which were then evaluated for pre‐specified criteria for relevance and quality assurance. A total of 50 articles, including 19 human studies and 31 animal studies, were selected for this review. Existing evidence supports the association of increased testosterone level and increased risk for alcohol use and AUD in males but results are inconclusive in females. In contrast, the evidence supports the association of increased estrogen level and increased alcohol use in females, with mixed findings reported in males. Much less is known about the impact of progestins on alcohol use and misuse in human subjects. Future observational and experimental studies conducted in both sexes with a comprehensive hormone panel are needed to elucidate the impact of the interplay between various sex hormone levels during various developmental stages on alcohol use‐related phenotypes and AUD.
Rich club and reward network connectivity as endophenotypes for alcohol dependence: a diffusion tensor imaging study
Authors: Zorlu Nabi , Çapraz Necip , Oztekin Esra , Bagci Başak , Di Biase Maria A. , Zalesky Andrew , Gelal Fazıl , Bora Emre , Durmaz Ercan , Beşiroğlu Lütfullah , Sarıçiçek Aybala
Published: December 2017

We aimed to examine the whole‐brain white matter connectivity and local topology of reward system nodes in patients with alcohol use disorder (AUD) and unaffected siblings, relative to healthy comparison individuals. Diffusion‐weighted magnetic resonance imaging scans were acquired from 18 patients with AUD, 15 unaffected siblings of AUD patients and 15 healthy controls. Structural networks were examined using network‐based statistic and connectomic analysis. Connectomic analysis showed a significant ordered difference in normalized rich club organization (AUD < Siblings < Controls). We also found rank ordered differences (Control > Sibling > AUD) for both nodal clustering coefficient and nodal local efficiency in reward system nodes, particularly left caudate, right putamen and left hippocampus. Network‐based statistic analyses showed that AUD group had significantly weaker connectivity than controls in the right hemisphere, mostly in the edges connecting putamen and hippocampus with other brain regions. Our results suggest that reward system network abnormalities, especially in subcortical structures, and impairments in rich‐club organization might be related to the familial predisposition for AUD.
Peri‐implant squamous cell carcinoma
Authors: Ito K , Takahashi K , Eda T , Kondoh T , Goss A
Published: December 2017

Peri‐implant squamous cell carcinoma is an uncommon pathological manifestation, whereas peri‐implantitis is commonly found in association with dental implants. Both present similarly with loss of supporting soft and hard tissue around dental implants; therefore, a careful differential diagnosis is required. The present case concerns a 62‐year‐old Japanese man who had a dental implant which had been in the left maxillary incisor region for 4 years who apparently developed peri‐implantitis. This did not respond to localized therapy and antibiotics so was referred for specialist surgical management. A biopsy confirmed it to be a squamous cell carcinoma rather than an inflammatory lesion. A literature review shows that this is an unusual presentation without a previous history of malignancy, mucosal disease or risk factors for cancers. Although rare, the possibility of peri‐implant squamous cell carcinoma should be borne in mind by all practitioners who monitor implant patients.