bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for the dimerization of Gemin5 and its role in protein recruitment and translation control
Authors: Moreno-Morcillo María , Francisco-Velilla Rosario , Embarc-Buh Azman , Fernández-Chamorro Javier , Ramón-Maiques Santiago , Martinez-Salas Encarnacion
Published: November 2019

In all organisms, a selected type of proteins accomplishes critical roles in cellular processes that govern gene expression. The multifunctional protein Gemin5 cooperates in translation control and ribosome binding, besides acting as the RNA-binding protein of the survival of motor neuron (SMN) complex. While these functions reside on distinct domains located at each end of the protein, the structure and function of the middle region remained unknown. Here, we solved the crystal structure of an extended tetratricopeptide (TPR)-like domain in human Gemin5 that self-assembles into a previously unknown canoe-shaped dimer. We further show that the dimerization module is functional in living cells driving the interaction between the viral-induced cleavage fragment p85 and the full-length Gemin5, which anchors splicing and translation members. Disruption of the dimerization surface by a point mutation in the TPR-like domain prevents this interaction and also abrogates translation enhancement induced by p85. The characterization of this unanticipated dimerization domain provides the structural basis for a role of the middle region of Gemin5 as a central hub for protein-protein interactions.
The therapeutic and diagnostic potential of regulatory noncoding RNAs in medulloblastoma
Authors: Joshi Piyush , Katsushima Keisuke , Zhou Rui , Meoded Avner , Stapleton Stacie , Jallo George , Raabe Eric , Eberhart Charles G , Perera Ranjan J
Published: November 2019

Medulloblastoma, a central nervous system tumor that predominantly affects children, always requires aggressive therapy. Nevertheless, it frequently recurs as resistant disease and is associated with high morbidity and mortality. While recent efforts to subclassify medulloblastoma based on molecular features have advanced our basic understanding of medulloblastoma pathogenesis, optimal targets to increase therapeutic efficacy and reduce side effects remain largely undefined. Noncoding RNAs (ncRNAs) with known regulatory roles, particularly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), are now known to participate in medulloblastoma biology, although their functional significance remains obscure in many cases. Here we review the literature on regulatory ncRNAs in medulloblastoma. In providing a comprehensive overview of ncRNA studies, we highlight how different lncRNAs and miRNAs have oncogenic or tumor suppressive roles in medulloblastoma. These ncRNAs possess subgroup specificity that can be exploited to personalize therapy by acting as theranostic targets. Several of the already identified ncRNAs appear specific to medulloblastoma stem cells, the most difficult-to-treat component of the tumor that drives metastasis and acquired resistance, thereby providing opportunities for therapy in relapsing, disseminating, and therapy-resistant disease. Delivering ncRNAs to tumors remains challenging, but this limitation is gradually being overcome through the use of advanced technologies such as nanotechnology and rational biomaterial design.
High growth rates of a dominant calanoid copepod in the northern San Francisco Estuary
Authors: Owens Stephanie , Ignoffo Toni R , Frantzich Jared , Slaughter Anne , Kimmerer Wim
Published: November 2019

We measured growth rates of the copepod Pseudodiaptomus forbesi in relation to food, environmental conditions and hydrology in the northern San Francisco Estuary, California, USA. We conducted 38 copepod growth-rate experiments during summers 2015–2017 at four sites in a tidal, freshwater channel that had strong gradients in environmental conditions. Copepod growth rates were measured using the artificial cohort method with an image analysis technique, and seston attributes were measured to investigate the effects of food quantity and quality on copepod growth rates. Growth rates ranging from 0.03 to 0.47 day−1 (median 0.30 day−1) and growth rates, chlorophyll, turbidity and total lipids in the channel decreased with distance downstream. Growth rates had a saturating response to chlorophyll and were generally higher than rates previously measured in larger estuarine channels, presumably because of higher chlorophyll and temperature in our study area. Growth rate was positively associated with biovolume of cyanobacteria but not with that of other major phytoplankton groups, which is consistent with a recent finding of high feeding of P. forbesi on cyanobacteria. This adds to the small but growing literature suggesting that crustacean planktons are able to overcome the nutritional deficiencies of cyanobacteria to grow and reproduce.
Association Between Self-Reported Spinal Morning Stiffness and Radiographic Evidence of Lumbar Disk Degeneration in Participants of the Cohort Hip and Cohort Knee (CHECK) Study
Authors: van den Berg Roxanne , Jongbloed Elisabeth M , Kuchuk Natalia O , Koes Bart W , Oei Edwin H G , Bierma-Zeinstra Sita M A , Luijsterburg Pim A J
Published: November 2019

Background

Low back pain (LBP) is very common and is a main cause of limited activity and work absence. Patients with LBP may also report spinal morning stiffness; this symptom could be useful for identifying subgroups with signs and symptoms related to spinal osteoarthritis.

Objective

This study investigated whether an association exists between reported spinal morning stiffness and radiographic evidence of lumbar disk degeneration (LDD) in people with LBP and a history of pain of the hip and/or knee.

Design

This cross-sectional study used 8-year follow-up data from the Cohort Hip and Cohort Knee study.

Methods

The association between spinal morning stiffness and radiographic LDD features was assessed with multivariable logistic regression models.

Results

The presence of osteophytes was significantly associated with spinal morning stiffness (odds ratio [OR] = 2.1 [95% confidence interval [CI] = 1.3–3.2]) as was the presence of grade 2 or 3 disk space narrowing (OR = 2.0 [95% CI = 1.1–3.5]). There was also a significant association between morning stiffness persisting for > 30 minutes and grade 2 osteophytes (OR = 2.6 [95% CI = 1.1–6.2]) and grade 1 disk space narrowing (OR = 2.0 [95% CI = 1.1–3.6]). Furthermore, there was a significant association between moderate spinal morning stiffness and the presence of osteophytes (OR = 2.0 [95% CI = 1.2–3.2]). Both the presence of osteophytes and disk space narrowing were significantly associated with severe spinal morning stiffness (for osteophytes: OR = 2.0 [95% CI = 1.2–3.7]; for narrowing at L1-S1: OR = 1.8 [95% CI = 1.1–3.1]).

Limitations

Only lumbar lateral radiographs were available for each participant, implying that the LDD features could have been underestimated. The quality of the radiographs was not consistent.

Conclusions

This study showed an association between self-reported spinal morning stiffness and symptomatic LDD. When morning stiffness lasted > 30 minutes, there was a significant association with the features of LDD. The association was stronger when the severity of spinal morning stiffness increased.
Robust, ECG-based detection of Sleep-disordered breathing in large population-based cohorts
Authors: Olsen Mads , Mignot Emmanuel , Jennum Poul Jorgen , Sorensen Helge Bjarup Dissing
Published: November 2019

Study Objectives

Up to 5% of adults in Western countries have undiagnosed sleep-disordered breathing (SDB). Studies have shown that electrocardiogram (ECG)-based algorithms can identify SDB and may provide alternative screening. Most studies, however, have limited generalizability as they have been conducted using the apnea-ECG database, a small sample database that lacks complex SDB cases.

Methods

Here, we developed a fully automatic, data-driven algorithm that classifies apnea and hypopnea events based on the ECG using almost 10 000 polysomnographic sleep recordings from two large population-based samples, the Sleep Heart Health Study (SHHS) and the Multi-Ethnic Study of Atherosclerosis (MESA), which contain subjects with a broad range of sleep and cardiovascular diseases (CVDs) to ensure heterogeneity.

Results

Performances on average were sensitivity(Se)=68.7%, precision (Pr)=69.1%, score (F1)=66.6% per subject, and accuracy of correctly classifying apnea–hypopnea index (AHI) severity score was Acc=84.9%. Target AHI and predicted AHI were highly correlated (R2 = 0.828) across subjects, indicating validity in predicting SDB severity. Our algorithm proved to be statistically robust between databases, between different periodic leg movement index (PLMI) severity groups, and for subjects with previous CVD incidents. Further, our algorithm achieved the state-of-the-art performance of Se=87.8%, Sp=91.1%, Acc=89.9% using independent comparisons and Se=90.7%, Sp=95.7%, Acc=93.8% using a transfer learning comparison on the apnea-ECG database.

Conclusions

Our robust and automatic algorithm constitutes a minimally intrusive and inexpensive screening system for the detection of SDB events using the ECG to alleviate the current problems and costs associated with diagnosing SDB cases and to provide a system capable of identifying undiagnosed SDB cases.
Self-reported sleep relates to hippocampal atrophy across the adult lifespan: results from the Lifebrain consortium
Authors: Fjell Anders M , Sørensen Øystein , Amlien Inge K , Bartrés-Faz David , Bros Didac Maciá , Buchmann Nikolaus , Demuth Ilja , Drevon Christian A , Düzel Sandra , Ebmeier Klaus P , Idland Ane-Victoria , Kietzmann Tim C , Kievit Rogier , Kühn Simone , Lindenberger Ulman , Mowinckel Athanasia M , Nyberg Lars , Price Darren , Sexton Claire E , Solé-Padullés Cristina , Pudas Sara , Sederevicius Donatas , Suri Sana , Wagner Gerd , Watne Leiv Otto , Westerhausen René , Zsoldos Enikő , Walhovd Kristine B
Published: November 2019

Objectives

Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.

Methods

Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.

Results

No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.

Conclusions

Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
Involvement of VNS NAC-domain transcription factors in tracheid formation in Pinus taeda
Authors: Akiyoshi Nobuhiro , Nakano Yoshimi , Sano Ryosuke , Kunigita Yusuke , Ohtani Misato , Demura Taku
Published: November 2019

Vascular plants have two types of water-conducting cells, xylem vessel cells (in angiosperms) and tracheid cells (in ferns and gymnosperms). These cells are commonly characterized by secondary cell wall (SCW) formation and programmed cell death (PCD), which increase the efficiency of water conduction. The differentiation of xylem vessel cells is regulated by a set of NAC (NAM, ATAF1/2 and CUC2) transcription factors, called the VASCULAR-RELATED NAC-DOMAIN (VND) family, in Arabidopsis thaliana Linne. The VNDs regulate the transcriptional induction of genes required for SCW formation and PCD. However, information on the transcriptional regulation of tracheid cell differentiation is still limited. Here, we performed functional analysis of loblolly pine (Pinus taeda Linne) VND homologs (PtaVNS, for VND, NST/SND, SMB-related protein). We identified five PtaVNS genes in the loblolly pine genome, and four of these PtaVNS genes were highly expressed in tissues with tracheid cells, such as shoot apices and developing xylem. Transient overexpression of PtaVNS genes induced xylem vessel cell-like patterning of SCW deposition in tobacco (Nicotiana benthamiana Domin) leaves, and up-regulated the promoter activities of loblolly pine genes homologous to SCW-related MYB transcription factor genes and cellulose synthase genes, as well as to cysteine protease genes for PCD. Collectively, our data indicated that PtaVNS proteins possess transcriptional activity to induce the molecular programs required for tracheid formation, i.e., SCW formation and PCD. Moreover, these findings suggest that the VNS–MYB-based transcriptional network regulating water-conducting cell differentiation in angiosperm and moss plants is conserved in gymnosperms.
Implementing Best Practices for the Provision of Long-acting Reversible Contraception: A Survey of Obstetrician-Gynecologists
Authors: Castleberry Neko M. , Stark Lauren , Schulkin Jay , Grossman Daniel
Published: November 2019

(Abstracted from Contraception 2019;100:123–127)

The most effective long-acting reversible contraceptives (LARCs) are intrauterine devices (IUDs) and contraceptive implants. Although LARCs are safe for nulliparous women and adolescents in the immediate postpartum and postabortion periods, the proportion of reproductive-aged women using contraceptives is low.
Use and Misuse of Opioids After Gynecologic Surgical Procedures
Authors: Wright Jason D. , Huang Yongmei , Melamed Alexander , Tergas Ana I. , St Clair Caryn M. , Hou June Y. , Khoury-Collado Fady , Ananth Cande V. , Neugut Alfred I. , Hershman Dawn L.
Published: November 2019

(Abstracted from Obstet Gynecol 2019;134(2):250–260)

The majority of opioid use disorders originate legally through prescriptions to the individual or through diverted medications; however, for various reasons, use often switches to use of cheaper illicit substances such as heroin. Recent literature has shown that 22% of opioids prescribed to opioid-naive patients are due to surgical procedures, with 1 study finding that of 36,000 patients who underwent surgery, 6% of patients prescribed a perioperative opioid developed persistent use more than 90 days postoperatively.
Maternal and Neonatal Outcomes Associated With Trophectoderm Biopsy
Authors: Zhang Wendy Y. , von Versen-Höynck Frauke , Kapphahn Kristopher I. , Fleischmann Raquel R. , Zhao Qianying , Baker Valerie L.
Published: November 2019

(Abstracted from Fertil Steril 2019;112:283–290)

Despite a widespread increase in the use of preimplantation genetic testing (PGT), there remains inconclusive examination of maternal and neonatal outcomes after pregnancy achieved through in vitro fertilization (IVF) with PGT. It has been proposed that abnormal placentation may occur at a higher rate in pregnancies after PGT due to the removal of trophectoderm cells during biopsy, leading to higher rates of preeclampsia and restricted fetal growth.
Physician Fertility: A Call to Action
Authors: Marshall Ariela L. , Arora Vineet M. , Salles Arghavan
Published: November 2019

Infertility is more prevalent in female physicians than in the U.S. general population. While pregnancy and its potential medical and career development consequences among physicians have been explored in the literature, infertility and its consequences remain understudied and unaddressed. Fertility issues are important for all physicians hoping to start families, including male physicians, transgender physicians, single physicians, and physicians with same-sex partners.

Infertility has numerous physical, emotional, and financial consequences and may have a negative impact on physician well-being. Options to preserve fertility (such as egg, embryo, and sperm cryopreservation) are available, yet physicians may not be aware of or have the financial ability to make use of such resources. Physician reproductive health, including the ability to build a family if and when a physician chooses, is a vital aspect of well-being. The risks and consequences of infertility and the management of fertility should be studied and addressed from policy and advocacy standpoints.

The authors, who have experienced and sought treatment for infertility, bring attention to the challenges around both physician infertility and preservation of fertility. They propose 3 strategies to address physician infertility: increasing fertility education and awareness starting at the undergraduate medical education level and continuing throughout training and practice, providing insurance coverage for and access to fertility assessment and management, and offering support for those undergoing fertility treatments. The authors believe that implementing these suggestions would make a significant positive impact on trainees and practicing physicians and help build a health care workforce that is healthy and well physically, emotionally, and financially.
Epstein–Barr virus molecular epidemiology and variants identification in head and neck squamous cell carcinoma
Authors: Karbalaie Niya Mohammad Hadi , Safarnezhad Tameshkel Fahimeh , Keyvani Hossein , Esghaei Maryam , Panahi Mahshid , Zamani Farhad , Tabibzadeh Alireza
Published: November 2019

Epstein-Barr virus (EBV) is known as one of the most widespread oncogenic viruses. Head and neck squamous cell carcinoma (HNSCC) is triggered by various risk factors. The aim of the present study was to determine the EBV infection rate, genotyping and variants frequency in HNSCC patients. In this cross-sectional study, 156 patients with HNSCC were enrolled. Formalin fixed paraffin embedded (FFPE) tissue samples were selected from hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. The EBV EBNA-3C, EBNA-1 and LMP-1 genes were amplified by PCR and then analyzed and confirmed by nucleotide sequencing. CLC work bench 5, MEGA6 and SPSS v.21 software were used for analysis the raw data. The mean age ± SD (years) of the all patients (n = 156) was 60.5 ± 12.6, in which of 121(77.6%) males it was 60.7 ± 11.9 and of 35 (22.4%) females it was 59.7 ± 14.9. Totally, 20 samples (12.8%) were found to be infected with EBV genome. The EBV genotypes 1 and 2 were calculated 90% (18/20) and 10% (2/20), respectively. vLMP-1 found in 40% (4/10) of all LMP-1 tested samples. Furthermore, the EBNA-1 predominant variants were P-ala followed by P-thr and also there were three P-ala-v2 sub variants. Statistics could not find any significant associations although there were some potentials. By our preliminary study in Iran, it revealed that EBV-1 is the predominant Epstein–Barr virus genotype in head and neck squamous cell carcinoma patients. vLMP-1 isolates showed lower survival rate than others. EBNA-1 variants had no significant association with any specific disease complication.
Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy
Authors: Harris Benjamin S. , Bishop Katherine C. , Kuller Jeffrey A. , Ford Anne C. , Muasher Lisa C. , Cantrell Sarah E. , Price Thomas M.
Published: November 2019

Objective:

The aim of the study was to review the role of hormone therapy in menopausal patients with breast cancer and gynecologic malignancies.

Methods:

We searched MEDLINE (via PubMed) using a combination of keywords and database-specific subject headings for the following concepts: menopause, hormone therapy, and cancer. Editorials, letters, case reports, and comments were excluded, as were non-English articles. Additional references were identified by hand-searching bibliographies of included articles. The searches yielded a total of 1,484 citations. All citations were imported into EndNote X9, where they were screened by the authors.

Results:

In breast cancer survivors, systemic hormone therapy is not recommended, whereas local low-dose estrogen therapy may be considered after discussion with the patient's oncologist. Among endometrial cancer survivors, hormone therapy is considered safe in low-risk cancers but should be avoided in high-risk subtypes. For survivors of epithelial ovarian cancer and cervical cancer, hormone therapy can be considered, but should be avoided in women with estrogen-sensitive histologic subtypes.

Conclusions:

The risks of hormone therapy should be assessed on an individual basis, with consideration of age, type of hormone therapy, dose, duration of use, regimen, route, and prior exposure. Systemic hormone therapy is not recommended in breast cancer survivors, whereas vaginal low-dose estrogen appears safe. Hormone therapy may be used by endometrial, cervical, and ovarian cancer survivors with low-risk, non-estrogen-receptor–positive subtypes.

Video Summary:
http://links.lww.com/MENO/A516.
Keratoconus Characteristics Used in Randomized Trials of Surgical Interventions—A Systematic Review
Authors: Baenninger Philipp B. , Bodmer Nicolas S. , Bachmann Lucas M. , Iselin Katja , Kaufmann Claude , Belin Michael W. , Thiel Michael A.
Published: November 2019

Purpose:

To investigate descriptions and inclusion criteria of keratoconus used in randomized trials assessing the efficacy of surgical and nonsurgical interventions.

Methods:

Systematic review: we searched (Pre-)Medline and the Cochrane Library from inception until December 2018 and checked the reference lists of included articles and reviews. We included randomized trials assessing the efficacy of any kind of keratoconus treatment. No language restrictions were imposed. We assessed articles against the inclusion criteria, extracted relevant data including any kind of keratoconus description, and examined the methodological quality.

Results:

Searches retrieved 459 nonduplicate records, and we included 57 randomized controlled trials investigating 9 different surgical interventions with the most used primary outcome measure being maximum keratometry. Only 15 (26.3%) described eligibility parameters regarding keratoconus staging/classification, of which 12 studies used the Amsler–Krumeich classification. Eleven studies were published before 1997 (before publication of the Consolidated Standards of Reporting Trials statement), and none of these described the use of a classification. From 1997 onward, 15 of 46 studies (32.6%) described the incorporation of a classification system (P = 0.051). The average methodological quality of included trails was modest.

Conclusions:

The evidence from randomized trials, even after introduction of the Consolidated Standards of Reporting Trials statement, remains ill-formed regarding a careful definition of keratoconus. This is unfortunate because imprecisions regarding the specification of included patients preclude clinicians to assess applicability, that is, the extent to which they can use inferences drawn from study participants regarding efficacy and adverse events in the care of individual patients.
Successful Descemet Membrane Endothelial Keratoplasty in Proven Herpetic Endothelial Decompensation Requires Intensive Antiviral Therapy
Authors: Friehmann Asaf , Myerscough James , Giannaccare Giuseppe , Mazzoni Maria , Bovone Cristina , Busin Massimo
Published: November 2019

Purpose:

To report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with intensive antiviral therapy for corneal edema secondary to herpes simplex virus type 1 (HSV-1)-mediated endotheliitis.

Methods:

All eyes with polymerase chain reaction positive for HSV-1 undergoing DMEK for endothelial decompensation between January 2014 and January 2018 were followed up prospectively at our tertiary referral center. All eyes had been free of active inflammation for a minimum of 9 months and were treated prophylactically with high-dose systemic and topical antivirals, which were continued for a prolonged period of time. Primary outcomes were the occurrence of immunological rejection and/or recurrence of endotheliitis, eventually resulting in graft failure. Secondary outcomes were best spectacle-corrected visual acuity and endothelial cell loss.

Results:

Four consecutive eyes of 4 patients were included with a mean (±SD) patient age of 68.5 ± 15.1 years. The postoperative follow-up averaged 22 months. No eyes exhibited any signs of immunologic rejection, recurrence of endotheliitis, or graft failure. Mean (±SD) decimal best spectacle-corrected visual acuity improved from 0.2 ± 0.1 to 0.7 ± 0.2 (P = 0.007), whereas mean (±SD) endothelial cell loss was 56% ± 10.2% at the final postoperative follow-up.

Conclusions:

DMEK is an effective option to treat corneal edema secondary to HSV-1-related endotheliitis. Intensive antiviral prophylaxis may reduce the risk of recurrence and subsequent graft failure.
Molecular Characterization of Streptococcus pyogenes Causing Invasive Disease in Pediatric Population in Spain A 12-year Study
Authors: Sánchez-Encinales Viviana , Ludwig Guillermo , Tamayo Esther , García-Arenzana Jose Maria , Muñoz-Almagro Carmen , Montes Milagrosa
Published: November 2019

Objectives:

To perform a comprehensive description of the epidemiology of Streptococcus pyogenes invasive disease in the pediatric population in 2 regions of Spain (Catalonia and Gipuzkoa) through 12 years.

Methods:

All S. pyogenes isolates causing invasive disease in pediatric patients between 2005 and 2016 were included. The emm-type and the presence of 13 exotoxin genes (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, ssa and slo) were determined in all 93 available isolates and the Multi Locus Sequece Typing in 10% of isolates of each different emm-type.

Results:

Overall, 103 cases of S. pyogenes invasive infections were detected: 77 in Catalonia and 26 in Gipuzkoa, being 50.5% females. The incidence rate per 100,000 children was 2.5 for Gipuzkoa and 2.6 for Catalonia, with no significant temporal trends. The median age was 30 months. The most frequent clinical presentations were: pneumonia (26.2%), bacteremia/sepsis (23.3%), septic arthritis/osteomyelitis (22.3%), cellulitis/mastoiditis (12.6%) and meningitis (6.8%). Eight children developed streptococcal toxic shock syndrome. Nine cases were preceded by varicella infection. The associated mortality rate was 3.9%. Three isolates were resistant to erythromycin, being one of them also resistant to clindamycin and 4 isolates were resistant to levofloxacine. Forteen different emm-types were detected being emm1/ST28 (40.9%) the most frequent clone in both regions followed by emm12/ST36-ST242, emm6/ST382, emm3/ST15, emm75/ST150 and emm4/ST38-39. speA gene was only detected in emm1 and emm3 isolates. Eight exotoxins were enough to assign an emm-type with a very high degree of accuracy (95%). The 30-valent vaccine would include 96.8% of isolates.
Clinical Course and Management of Dengue in Children Admitted to Hospital
Authors: Karyanti Mulya Rahma , Uiterwaal Cuno S.P.M. , Hadinegoro Sri Rezeki , Jansen Maria A.C. , Heesterbeek J.A.P. Hans , Hoes Arno W. , Bruijning-Verhagen Patricia
Published: November 2019

Background:

Dengue incidence is rising globally which was estimated 100 million per year, whereas in Indonesia was estimated 7.5 million per year. Dengue clinical course varies from mild dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Patients, clinicians and care facilities would benefit if reliable predictors can determine at admission which cases with clinically suspected dengue will progress to DHF or DSS.

Methods:

From 2009 through 2013, a cohort of 494 children admitted with clinically suspected dengue at a tertiary care hospital in Jakarta, Indonesia, was followed until discharge. We evaluated the clinical course and disease outcome of admitted patients and estimated the burden of dengue cases hospitalized over time.

Results:

Of all 494 children, 185 (37%) were classified at admission as DF, 158 (32%) as DHF and 151 (31%) as DSS. Of DF patients, 52 (28%) progressed to DHF or DSS, 10 (5%) had other viral diseases. Of DHF patients, 9(6%) progressed to DSS. Of 33 routinely collected parameters at admission, duration of fever ≤4 days was the only significant predictor of disease progression (P = 0.01). Five cases (3%) admitted with DSS died. Between 2009 and 2013, annual dengue admissions declined, while distribution of disease severity remained stable.

Conclusions:

Almost a third of children admitted to tertiary care with clinically suspected DF progress to DHF or DSS. Among routinely collected parameters at admission, only fever duration was significantly associated with clinical progression, emphasizing unpredictability of dengue disease course from parameters currently routinely collected.
Systematic Review on the Acute Cost-of-illness of Sepsis and Meningitis in Neonates and Infants
Authors: Salman Omar , Procter Simon R. , McGregor Callum , Paul Proma , Hutubessy Raymond , Lawn Joy E. , Jit Mark
Published: November 2019

Background:

Sepsis and meningitis in neonates and infants are a source of substantial morbidity, mortality and economic loss. The objective of this review is to estimate the acute costs associated with treating sepsis, meningitis and meningococcal septicemia, in neonates and infants, worldwide.

Methods:

The electronic databases Medline, Embase and EconLit were searched and exported on November 24, 2018. Studies that reported an average hospitalization cost for confirmed cases of sepsis, meningitis or meningococcal septicemia were eligible for our review. Descriptive data were extracted and reported costs were inflated and converted. A narrative synthesis of the costs was conducted.

Results:

Our review identified 20 studies reporting costs of sepsis, meningitis and/or meningococcal septicemia. Costs ranged from $55 to $129,632 for sepsis and from $222 to $33,635 for meningitis (in 2017 US dollars). One study estimated the cost of meningococcal septicemia to be $56,286. All reported costs were estimated from the perspective of the healthcare provider or payer. Most studies were from the United States, which also had the highest costs. Only a few studies were identified for low- and middle-income countries, which reported lower costs than high-income countries for both sepsis and meningitis.

Conclusions:

Sepsis and meningitis in neonates and infants are associated with substantial costs to the healthcare system and showed a marked difference across global income groups. However, more research is needed to inform costs in low- and middle-income settings and to understand the economic costs borne by families and wider society.
Cytomegalovirus Seroprevalence and Birth Prevalence of Congenital CMV Infection in Bosnia and Herzegovina
Authors: Arapović Jurica , Rajič Borko , Pati Sunil , Brizić Ilija , Azinović Igor , Šušak Božo , Ostojić Maja , Tutiš Borka , Raguž Ana Boban , Tomić Vajdana , Jonjić Stipan , Boppana Suresh
Published: November 2019

Background:

Congenital cytomegalovirus infection (cCMV) is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in developed countries. Although high cCMV rates have been reported in populations with high seroprevalence, the cCMV prevalence in low/middle-income countries in Europe has not been defined.

Objective:

To determine cytomegalovirus (CMV) seroprevalence and the cCMV prevalence in Bosnia and Herzegovina.

Methods:

Between March 2010 and February 2019, 5222 sera samples from patients seen at the University Clinical Hospital Mostar were tested for CMV IgG. The cord blood samples collected from 2091 infants between July 2011 and January 2013 were analyzed for CMV IgG and CMV DNA. The cCMV prevalence was determined by testing saliva swabs from 1293 infants between November 2015 and October 2016.

Results:

The overall CMV IgG prevalence was 81.4% (95% confidence interval: 0.8–0.82). Significantly higher prevalence was observed among females (84.9%) than in males (77.0%), and the rate increased from 50.8% in the 1 to 5 years group to 97.7% in the group > 65 years old. Most cord blood samples (2091/1925, 92.1%) were CMV IgG positive, and 2 (0.1%) were CMV DNA positive. Of the 1293 saliva swabs, 8 (0.62%; 95% confidence interval: 0.3–1.2) were CMV positive. All 8 infected infants had asymptomatic cCMV, and none had SNHL at 18 months of age.

Conclusions:

In a highly CMV seropositive population, the prevalence of cCMV was lower compared with that reported from other low/middle-income countries populations. None of the infected infants had symptomatic infection or SNHL at 18 months.
Complications of Otitis Media and Sinusitis Caused by Streptococcus anginosus Group Organisms in Children
Authors: McNeil J. Chase , Dunn James J. , Kaplan Sheldon L. , Vallejo Jesus G.
Published: November 2019

Background:

The Streptococcus anginosus group (SAG, S. anginosus, S. intermedius and S. constellatus) are often associated with severe disease and abscess formation. In our institution, we observed an apparent increase in frequency of intraorbital and intracranial infections resulting from SAG at Texas Children’s Hospital. We undertook a retrospective review to describe the frequency and clinical features of these infections.

Methods:

We reviewed the database of the microbiology laboratory at Texas Children’s Hospital from 2011 to 2018 for SAG-positive cultures. Cases included were those associated with (1) either otitis media or sinusitis and (2) Pott’s puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging. The number of overall diagnoses were determined using diagnostic codes and used to estimate the proportion of disease caused by SAG.

Results:

Ninety-five cases were identified meeting inclusion criteria. The median age of patients was 11.4 years, and 75.8% were previously healthy. S. intermedius was most commonly isolated (80%) followed by S. constellatus (12.6%) and S. anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention. 8.4% of patients experienced persistent neurologic deficits. We observed a significant increase in disease incidence during the study period; in addition, the overall proportion of all intracranial infections caused by SAG increased.

Conclusions:

Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity. These infections are becoming increasingly common at our center although the precise reason for this temporal trend is unclear.
Meta-analysis of the Clinical Efficacy and Safety of High- and Low-dose Methylprednisolone in the Treatment of Children With Severe Mycoplasma Pneumoniae Pneumonia
Authors: Sun Lin-Li , Ye Chao , Zhou Yu-Lu , Zuo Shan-Ru , Deng Zhen-Zhen , Wang Chun-Jiang
Published: November 2019

Background:

Mycoplasma pneumoniae pneumonia is generally a self-limiting disease, but it can develop into severe Mycoplasma pneumoniae pneumonia (SMPP). Immunologic mechanisms are thought to play an important role in the pathogenesis of SMPP. Therefore, the use of systemic glucocorticoids may have beneficial effects. However, to date, the use of glucocorticoid therapy in SMPP is limited to small case series, and the glucocorticoid dosage for children with SMPP has not been established.

Methods:

Here, we used a meta-analysis method to collect data from randomized control trials of different doses of methylprednisolone in SMPP to assess the safety and efficacy of treatment with low- versus high-dose methylprednisolone in children with SMPP.

Results:

We included 13 Chinese randomized control trials that included 1049 children. The high- and low-dose groups were comprised of 524 and 525 children, respectively. The high-dose group was significantly more effective than the low-dose group in clinical efficacy [risk ratio = 1.30, 95% confidence interval (CI) (1.23, 1.38), P < 0.05]. In addition, compared with low-dose methylprednisolone, high-dose methylprednisolone significantly shortened hospital stays and antipyretic therapy, pulmonary rales disappearance, cough disappearance and pulmonary shadow absorption times. There was no significant difference in adverse events between the high- and low-dose groups: risk ratio= 0.85, 95% CI (0.53, 1.36), P > 0.05.

Conclusions:

We conclude that high-dose methylprednisolone is effective in the treatment of SMPP without increasing the incidence of adverse reactions.
Epidemiology and Microbiology of Bacterial Bloodstream Infection in a Tertiary Hospital in Nigeria
Authors: Iliyasu Garba , Dayyab Farouq Muhammad , Aminu Aliyu , Halilu Sadiq , Abubakar Salisu , Inuwa Salisu , Habib Abdulrazaq Garba
Published: November 2019

Background

Bacterial bloodstream infections (BSIs) are a significant cause of morbidity and mortality among hospitalized patients, and data in resource-limited countries are sparse.

Methods

A hospital-wide retrospective analysis of microbiologically proven bacteremia was conducted. Sociodemographic data, comorbidities, bacterial isolates, and their antimicrobial susceptibility pattern were recorded.

Results

Of the 276 episodes of bacteremia studied, 130 (47.1%) occurred in females. The overall mean age was 15.29 ± 23.22 years. Community-acquired BSI was seen in 179 (65.0%) of the patients, whereas 97 (35%) was hospital-acquired BSI. Gram-negative bacteria 158 (57.2%) were the leading cause of BSI. More than 60% of the isolates were resistant to commonly prescribed antibiotics, especially trimethoprim-sulfamethoxazole, ampicillin, and amoxicillin–clavulanic acid.

Conclusions

Gram-negative bacteria are the leading cause of bacteremia with resistance to commonly prescribed antibiotics.
A Case of Sphingobacterium spiritivorum Bacteremia and Literature Review
Authors: Sahar Najmus , Shahid Mohammad , Ali Asghar
Published: November 2019

High sphingophospholipids in the cell membrane characterize the genus Sphingobacterium. Sphingobacterium spiritivorum is a gram-negative, non–spore-forming, nonmotile bacterium that is ubiquitous in nature and rarely involved in human disease. It is intrinsically resistant to many antimicrobials, which if underrecognized can be potentially life-threatening. We present a case of a 72-year-old white man who presented with cellulitis and sepsis secondary to S. spiritivorum.
Previously Unreported Presentation of Anaplasmosis in an Endemic Area
Authors: Saha Biplab K. , Chieng Hau , Itty Ria , Bonnier Alyssa , Shkolnik Boris , Beegle Scott
Published: November 2019

Human granulocytic anaplasmosis or anaplasmosis is a zoonotic disease that is endemic to certain geographic areas of the United States. Anaplasmosis is caused by Anaplasma phagocytophilum, an intracellular bacterium that is transmitted to humans by deer ticks. The clinical presentation can vary from a subclinical infection to fulminant disease resulting in multiorgan failure and death. Patients commonly present with fever, malaise, myalgia, headache, nausea, vomiting, arthralgia, and cough. Central nervous system involvement has also been reported. Here, we present 2 cases that presented with significant diagnostic challenge being the first reported cases of pleuropericarditis (case 1) and autoimmune hemolytic anemia due to cold agglutinin disease (case 2) secondary to anaplasmosis. Knowledge of these complications from human granulocytic anaplasmosis will help clinicians to make an early diagnosis and institute appropriate treatment, especially in an endemic setting.
A Single-Center Experience and Literature Review of Management Strategies for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Patients
Authors: Majeed Aneela , Larriva Marti M. , Iftikhar Ahmad , Mushtaq Adeela , Campbell Patrick , Malik Mustafa Nadeem , Rafae Abdul , Zar Muhammad Abu , Kamal Ahmad , Lakhani Midhat , Khalid Nageena Rani , Zangeneh Tirdad T. , Anwer Faiz
Published: November 2019

Introduction

The aim of our study is to evaluate risk factors associated with the development ofClostridium difficileinfection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence, and report outcomes of CDI in our patient population.

Methods

We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI.

Results

The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, sex, cancer type, and transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only 2 of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus, and no patient underwent colectomy. There was no mortality associated with CDI at our center.

Conclusions

Clostridium difficileinfection has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, sex, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of more than 4 lines of antibiotics were observed among those with CDI compared with those without CDI.
A functional polymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients
Authors: Benavides Rodrigo , Vsevolozhskaya Olga , Cattaneo Stefano , Zaykin Dmitri , Brenton Ashley , Parisien Marc , Verma Vivek , Khoury Samar , Gilron Ian , Diatchenko Luda
Published: November 2019

Many genetic markers have been associated with variations in treatment response to analgesics, but none have been assessed in the context of combination therapies. In this study, the treatment effects of nortriptyline and morphine were tested for an association with genetic markers relevant to pain pathways. Treatment effects were determined for single and combination therapies. A total of 24 functional single nucleotide polymorphisms were tested within the gene loci of mu-opioid receptor (OPRM1) gene locus, ATP-Binding Cassette B1 Transporter (ABCB1), Cytochrome P450 gene family (CYP2C19andCYP2D6), catecholamine inactivator Catechol-O-Methyl Transferase (COMT), and serotonin receptor 2A (HTR2A). Genotyping was performed in a population of neuropathic pain patients who previously participated in a clinical trial. For monotherapy, neither nortriptyline nor morphine responses were associated with single nucleotide polymorphisms. However, for nortriptyline + morphine combination therapy, the single nucleotide polymorphism rs1045642 within the drug efflux pump ABCB1 transporter significantly predicted analgesic response. The presence of the C allele accounted for 51% of pain variance in this subgroup in response to combination treatment. The T-allele homozygotes demonstrated only 20% improvement in pain scores, whereas the C-allele homozygotes 88%. There was no significant contribution of rs1045642 to the medication side effects under all treatment conditions. The UK Biobank data set was then used to validate this genetic association. Here, patients receiving similar combination therapy (opioid + tricyclic antidepressant) carrying the C allele of rs1045642 displayed 33% fewer body pain sites than patients without that allele, suggesting better pain control. In all, our results show a robust effect of the rs1045642 polymorphism in response to chronic pain treatment with a nortriptyline + morphine combination.
Effects of eHealth-Based Interventions on Adherence to Components of Cardiac Rehabilitation
Authors: Kebapci Ayda , Ozkaynak Mustafa , Lareau Suzanne C.
Published: November 2019

Objective

The aim of this study was to determine the effects of eHealth-based interventions on patient adherence to components of cardiac rehabilitation (CR).

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guided this review. Medline, CINAHL, Embase, and Cochrane Library databases were searched for studies published from January 1996 to December 2017. All studies were included in which eHealth-based components of CR and its effects on patient adherence were measured. Because this review included a heterogeneous group of study designs, the authors qualitatively described the effect of eHealth on adherence into a narrative approach.

Results

A total of 1520 studies were identified, with 1415 excluded after screening. Of the remaining 105 studies, 90 were excluded after full text assessment, leaving 15 studies for analysis. Most (11) of the 15 studies reported on medication adherence. Other studies focused on adherence to diet, physical activity, vital signs, weight, step counts, smoking, and fluid restriction. The type of eHealth used also varied, ranging from telemonitoring and web-based applications to telephone calls. Of the 15 studies, 7 reported significant improvements with eHealth-based components of CR on adherence.

Discussion and Conclusion

This review summarizes the effects of eHealth on components of CR and revealed variations in measurement and evaluation methods. The telemonitoring and web-based applications for self-care behaviors were most effective in promoting adherence. The measurement of adherence should be based on an explicit definition of adherence and should be measured with validated scales tested in the CR population.
Binge eating behavior among a cohort of normal weight college women
Authors: Kells Meredith , Kelly-Weeder Susan
Published: November 2019

Background and purpose:

Binge eating (BE) has been linked to the development of eating disorders and obesity, and it has been reported in college women. Few studies investigate BE by weight category. The purpose of this study was to examine BE in “normal” weight college women.

Methods:

Secondary analysis of Web-based survey at a private university in the northeastern United States.

Results:

Sample was 317 female subjects, 75.4% were White. Binge eating was reported by 99 women (31.2%); 7.6% of binge eaters were underweight, 73.5% normal weight, 15.3% overweight, and 4.1% obese. Normal weight binge eaters were more likely to purge (x
2 = 6.830; p = .033) and overexercise (x
2 = 15.179, p = .019). All binge eaters reported feeling sad, guilty, or distressed after eating and weight dissatisfaction. Normal weight binge eaters reported negative affect before (x
2 = 33.187; p < .001) and after eating (x
2 = 36.329; p < .001) more frequently than normal weight non–binge eaters. Normal weight binge eaters more often described themselves as overweight when compared with normal weight non–binge eaters (x
2 = 9.267; p = .026).

Implications for practice:

Nearly one third of college women report BE, the majority are of normal weight. These women are more likely to engage in compensatory mechanisms and have distorted body image and a negative affective state with eating. Findings highlight the importance of screening for BE in college women regardless of weight.