bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung function abnormalities in HIV‐infected adults and children
Authors: Calligaro Gregory L. , Gray Diane M. 
Published: September 2014

AbstractDespite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function.This review therefore summarizes the lung function abnormalities described in HIV‐positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability.
Effect of increasing respiratory rate on airway resistance and reactance in COPD patients
Authors: Nakagawa Misa , Hattori Noboru , Haruta Yoshinori , Sugiyama Aya , Iwamoto Hiroshi , Ishikawa Nobuhisa , Fujitaka Kazunori , Murai Hiroshi , Tanaka Junko , Kohno Nobuoki 
Published: September 2014

AbstractBackground and objectiveAirway resistance and reactance measured by forced oscillometry have been used to measure the severity of airway obstruction in chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to assess the effects of tachypnoea on airway resistance and reactance and to correlate these with the severity of dyspnoea. We also evaluated the effects of short‐acting β2‐agonist (SABA) on these measurements.MethodsAirway resistance and reactance were measured with an impulse oscillation system (IOS) in 20 COPD and 10 control participants during resting respiration and metronome‐paced breathing at 20, 30 and 40 tidal breaths/min. The same measurements were made for COPD patients after SABA inhalation. Dyspnoea was evaluated using the modified Medical Research Council (MRC) scale.ResultsIn patients with COPD, higher respiratory rates increased expiratory and inspiratory resistance at 5 Hz (R5), the difference in respiratory resistance at 5 Hz and 20 Hz (R5–R20), resonant frequency and decreased expiratory reactance. The decreases in expiratory reactance from 20 to 40 tidal breaths/min were significantly correlated with MRC scores. SABA inhalation significantly reduced the effect of increased respiratory rate on the reactance measurements.ConclusionsCharacteristic changes in IOS measurements, particularly expiratory reactance, induced by increased respiratory rates, were correlated with severity of dyspnoea in COPD patients during their daily lives. IOS and paced breathing may be useful for assessing breathlessness in COPD.
Bayesian Semiparametric Analysis of Semicompeting Risks Data: Investigating Hospital Readmission After a Pancreatic Cancer Diagnosis
Authors: Lee Kyu Ha , Haneuse Sebastien , Schrag Deborah , Dominici Francesca 
Published: September 2014

SummaryIn the USA, the Centers for Medicare and Medicaid Services use 30-day readmission, following hospitalization, as a proxy outcome to monitor quality of care. These efforts generally focus on treatable health conditions, such as pneumonia and heart failure. Expanding quality-of-care systems to monitor conditions for which treatment options are limited or non-existent, such as pancreatic cancer, is challenging because of the non-trivial force of mortality; 30-day mortality for pancreatic cancer is approximately 30%. In the statistical literature, data that arise when the observation of the time to some non-terminal event is subject to some terminal event are referred to as ‘semicompeting risks data’. Given such data, scientific interest may lie in at least one of three areas: estimation or inference for regression parameters, characterization of dependence between the two events and prediction given a covariate profile. Existing statistical methods focus almost exclusively on the first of these; methods are sparse or non-existent, however, when interest lies with understanding dependence and performing prediction. We propose a Bayesian semiparametric regression framework for analysing semicompeting risks data that permits the simultaneous investigation of all three of the aforementioned scientific goals. Characterization of the induced posterior and posterior predictive distributions is achieved via an efficient Metropolis–Hastings–Green algorithm, which has been implemented in an R package. The framework proposed is applied to data on 16051 individuals who were diagnosed with pancreatic cancer between 2005 and 2008, obtained from Medicare part A. We found that increased risk for readmission is associated with a high comorbidity index, a long hospital stay at initial hospitalization, non-white race, being male and discharge to home care.
Instituting Best Practice for Monitoring for Opioid‐Induced Advancing Sedation in Hospitalized Patients
Authors: Jungquist Carla R. , Pasero Chris , Tripoli Nicole M. , Gorodetsky Rachel , Metersky Mark , Polomano Rosemary C. 
Published: September 2014

ABSTRACTBackgroundAdverse events related to opioid‐induced unintended advancing sedation and respiratory depression in hospitalized patients are occurring with increased frequency, and these adverse events can have a negative impact on quality and cost outcomes.AimThe goal of this paper is to inform nurses on best practices for preventing opioid‐induced advancing sedation and respiratory depression, and to inform nurse leaders on implementation strategies to guide change in policies and practice.MethodsThis paper presents an evidenced‐based systematic approach for organizations to use in implementing strategies to reduce adverse events secondary to opioid‐induced advancing sedation and respiratory depression in the hospitalized adult patient.ResultsAn action‐oriented framework was developed based on the authors’ experiences, strategies recommended by the Institute for Healthcare Improvement (IHI), the National Association of Healthcare Quality (NAHQ), and expert consensus‐based best monitoring practices.Linking Evidence to ActionNurse executives and nurse managers assume accountability for ensuring that patient care is aligned with the best evidence, practices, and regulatory mandates. The framework presented in this paper can help prevent opioid‐induced advancing sedation and respiratory depression, and assist nurse leaders in implementation strategies to guide policies and practice.
Angiotensin type 1A receptor expression in C1 neurons of the rostral ventrolateral medulla contributes to the development of angiotensin‐dependent hypertension
Authors: Jancovski Nikola , Carter David A. , Connelly Angela A. , Stevens Elyse , Bassi Jaspreet K. , Menuet Clement , Allen Andrew M. 
Published: September 2014

New Findings
What is the central question of this study?
This study addresses the mechanism by which deletion of angiotensin II type 1A receptors from catecholaminergic neurons reduces angiotensin‐dependent hypertension, as well as the identity of the cells involved.

What is the main finding and its importance?
Deletion of angiotensin II type 1A receptors from catecholaminergic neurons results in reduced sympathetic nerve activation and fluid and electrolyte retention during angiotensin infusion. The C1 neurons of the rostral ventrolateral medulla are involved in the later phase of the hypertension. We demonstrate that at least two different populations of catecholaminergic neurons are involved in the sympathetic nerve activation required for the full development of angiotensin‐dependent hypertension.

Chronic low‐dose systemic infusion of angiotensin II induces hypertension via activation of the angiotensin II type 1A receptor (AT1AR). Previously, we have demonstrated that expression of the AT1AR on catecholaminergic neurons is necessary for the full development of angiotensin‐dependent hypertension. In the present study, we examined the mechanism by which selective deletion of the AT1AR from these cells affects the development of hypertension. We also tested the hypothesis that AT1ARs expressed by catecholaminergic C1 neurons in the rostral ventrolateral medulla play an important role in angiotensin‐induced hypertension. A Cre‐lox approach was used to delete the AT1AR from all catecholaminergic cells or from C1 neurons selectively. Subcutaneous administration of angiotensin II induced hypertension in all mice, with delayed onset and reduced maximal response in the global AT1AR catecholaminergic knockout mice. The AT1AR catecholaminergic knockout mice had decreased renal fluid and electrolyte retention and urinary noradrenaline excretion. The blood pressure response was reduced only during the second week of angiotensin II infusion in the mice with selective C1 AT1AR deletion, demonstrating that AT1AR expression by C1 neurons plays a moderate role in angiotensin‐induced hypertension. The difference in the time course of development of hypertension between the mice with global AT1AR knockout from catecholaminergic cells and the mice with C1 AT1AR deletion suggests that other catecholaminergic neurons are important.
Periaqueductal grey cyclooxygenase‐dependent facilitation of C‐nociceptive drive and encoding in dorsal horn neurons in the rat
Authors: Leith J. Lianne , Wilson Alex W. , You Hao‐Jun , Lumb Bridget M. , Donaldson Lucy F. 
Published: September 2014

Key points
A‐ and C‐nociceptors make different contributions to pain. They signal fast and slow pain, respectively, and C‐nociceptors drive central sensitisation.
Cyclooxygenase‐1 (COX‐1)‐dependent descending facilitation from the periaqueductal grey (PAG) affects C‐nociceptor spinal reflexes, but leaves A‐nociceptor reflexes largely untouched.
We studied the responses of spinal wide dynamic‐range dorsal horn neurons to A‐ and C‐nociceptor stimulation before and after COX‐1 inhibition in the PAG.
Inhibition of COX‐1 descending facilitation disrupted the neuronal encoding of C‐nociceptor information, but left the encoding of A‐nociceptor information untouched.
Inhibition of COX‐1‐dependent descending facilitation increased the activation threshold of wide dynamic range neurons to both A‐ and C‐nociceptor input.
The COX‐dependent descending system from the PAG can therefore control the amount of C‐nociceptor information reaching the CNS (slow, burning, aching, debilitating pain) without affecting the protective A‐nociceptor information (sharp, well‐localised, protective pain).
AbstractThe experience of pain is strongly affected by descending control systems originating in the brainstem ventrolateral periaqueductal grey (VL‐PAG), which control the spinal processing of nociceptive information. A‐ and C‐fibre nociceptors detect noxious stimulation, and have distinct and independent contributions to both the perception of pain quality (fast and slow pain, respectively) and the development of chronic pain. Evidence suggests a separation in the central processing of information arising from A‐ vs. C‐nociceptors; for example, inhibition of the cyclooxygenase‐1 (COX‐1)–prostaglandin system within the VL‐PAG alters spinal nociceptive reflexes evoked by C‐nociceptor input in vivo via descending pathways, leaving A‐nociceptor‐evoked reflexes largely unaffected. As the spinal neuronal mechanisms underlying these different responses remain unknown, we determined the effect of inhibition of VL‐PAG COX‐1 on dorsal horn wide dynamic‐range neurons evoked by C‐ vs. A‐nociceptor activation. Inhibition of VL‐PAG COX‐1 in anaesthetised rats increased firing thresholds of lamina IV–V wide dynamic‐range dorsal horn neurons in response to both A‐ and C‐nociceptor stimulation. Importantly, wide dynamic‐range dorsal horn neurons continued to faithfully encode A‐nociceptive information, even after VL‐PAG COX‐1 inhibition, whereas the encoding of C‐nociceptor information by wide dynamic‐range spinal neurons was significantly disrupted. Dorsal horn neurons with stronger C‐nociceptor input were affected by COX‐1 inhibition to a greater extent than those with weak C‐fibre input. These data show that the gain and contrast of C‐nociceptive information processed in individual wide dynamic‐range dorsal horn neurons is modulated by prostanergic descending control mechanisms in the VL‐PAG.
Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition
Authors: Yoon Bo‐Eun , Woo Junsung , Chun Ye‐Eun , Chun Heejung , Jo Seonmi , Bae Jin Young , An Heeyoung , Min Joo Ok , Oh Soo‐Jin , Han Kyung‐Seok , Kim Hye Yun , Kim Taekeun , Kim Young Soo , Bae Yong Chul , Lee C. Justin 
Published: September 2014

Key points
Here we show that glial gamma aminobutyric acid (GABA) is produced by monoamine oxidase B (MAOB), utilizing a polyamine, putrescine.
The concentration of GABA in Bergmann glial cells is estimated to be around 5–10 mM.
General gene silencing of MAOB resulted in elimination of tonic GABA currents recorded from granule cells in the cerebellum and medium spiny neurons (MSN) in the striatum.
Glial‐specific rescue of MAOB resulted in complete restoration of tonic GABA currents.
Our results identify MAOB as a synthesizing enzyme of glial GABA, which is released to mediate tonic inhibition in the cerebellum and striatum.
AbstractGABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5–10 mm by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca2+‐induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial‐specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain.
Active Commuting to School in Mexican Adolescents: Evidence From the Mexican National Nutrition and Health Survey
Authors: Jáuregui Alejandra , Medina Catalina , Salvo Deborah , Barquera Simon , Rivera-Dommarco Juan A. 
Published: September 2014

Background:Travel to school offers a convenient way to increase physical activity (PA) levels in youth. We examined the prevalence and correlates of active commuting to school (ACS) in a nationally representative sample of Mexican adolescents. A secondary objective was to explore the association between ACS and BMI status.Methods:Using data of adolescents (10–14 years old) from the 2012 Mexican National Health and Nutrition Survey (n = 2952) we ran multivariate regression models to explore the correlates of ACS and to test the association between ACS and BMI z-score or overweight/obesity. Models were adjusted for potential confounders and design effect.Results:70.8% of adolescents engaged in ACS (walking: 68.8%, bicycling: 2.0%). ACS was negatively associated with travel time, age, mother’s education level, household motor vehicle ownership, family socioeconomic status, and living in urban areas or the North region of the country (P < .05). Time in ACS was negatively associated with overweight/obesity: Each additional minute of ACS was associated with a 1% decrease in the odds for being overweight or obese (P < .05).Conclusions:Potential correlates of ACS that may result in benefits for Mexican adolescents are identified. More studies on this relationship are needed to develop interventions aimed at increasing PA through ACS in Mexico.
Multiple Influenza A (H3N2) Mutations Conferring Resistance to Neuraminidase Inhibitors in a Bone Marrow Transplant Recipient
Authors: Eshaghi Alireza , Shalhoub Sarah , Rosenfeld Paul , Li Aimin , Higgins Rachel R. , Stogios Peter J. , Savchenko Alexei , Bastien Nathalie , Li Yan , Rotstein Coleman , Gubbay Jonathan B. 
Published: September 2014

ABSTRACTImmunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Δ245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.
Bacillus anthracis GrlA
V96A
Topoisomerase IV, a Quinolone Resistance Mutation That Does Not Affect the Water-Metal Ion Bridge
Authors: Aldred Katie J. , Breland Erin J. , McPherson Sylvia A. , Turnbough Charles L. , Kerns Robert J. , Osheroff Neil 
Published: September 2014

ABSTRACT

The rise in quinolone resistance is threatening the clinical use of this important class of broad-spectrum antibacterials. Quinolones kill bacteria by increasing the level of DNA strand breaks generated by the type II topoisomerases gyrase and topoisomerase IV. Most commonly, resistance is caused by mutations in the serine and acidic amino acid residues that anchor a water-metal ion bridge that facilitates quinolone-enzyme interactions. Although other mutations in gyrase and topoisomerase IV have been reported in quinolone-resistant strains, little is known regarding their contributions to cellular quinolone resistance. To address this issue, we characterized the effects of the V96A mutation in the A subunit of
Bacillus anthracis
topoisomerase IV on quinolone activity. The results indicate that this mutation causes an ∼3-fold decrease in quinolone potency and reduces the stability of covalent topoisomerase IV-cleaved DNA complexes. However, based on metal ion usage, the V96A mutation does not disrupt the function of the water-metal ion bridge. A similar level of resistance to quinazolinediones (which do not use the bridge) was seen. V96A is the first topoisomerase IV mutation distal to the water-metal ion bridge demonstrated to decrease quinolone activity. It also represents the first A subunit mutation reported to cause resistance to quinazolinediones. This cross-resistance suggests that the V96A change has a global effect on the structure of the drug-binding pocket of topoisomerase IV.
Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase
Authors: Bai Tingli , Zhang Daozhong , Lin Shuangjun , Long Qingshan , Wang Yemin , Ou Hongyu , Kang Qianjin , Deng Zixin , Liu Wen , Tao Meifeng 
Published: September 2014

ABSTRACT

Lipstatin, isolated from
Streptomyces toxytricini
as a potent and selective inhibitor of human pancreatic lipase, is a precursor for tetrahydrolipstatin (also known as orlistat, Xenical, and Alli), the only FDA-approved antiobesity medication for long-term use. Lipstatin features a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-β-lactone structure with an
N
-formyl-
l
-leucine group attached as an ester to the 5-hydroxy group. It has been suggested that the α-branched 3,5-dihydroxy fatty acid β-lactone moiety of lipstatin in
S. toxytricini
is derived from Claisen condensation between two fatty acid substrates, which are derived from incomplete oxidative degradation of linoleic acid based on feeding experiments. In this study, we identified a six-gene operon (
lst
) that was essential for the biosynthesis of lipstatin by large-deletion, complementation, and single-gene knockout experiments.
lstA
,
lstB
, and
lstC
, which encode two β-ketoacyl–acyl carrier protein synthase III homologues and an acyl coenzyme A (acyl-CoA) synthetase homologue, were indicated to be responsible for the generation of the α-branched 3,5-dihydroxy fatty acid backbone. Subsequently, the nonribosomal peptide synthetase (NRPS) gene
lstE
and the putative formyltransferase gene
lstF
were involved in decoration of the α-branched 3,5-dihydroxy fatty acid chain with an N-formylated leucine residue. Finally, the 3β-hydroxysteroid dehydrogenase-homologous gene
lstD
might be responsible for the reduction of the β-keto group of the biosynthetic intermediate, thereby facilitating the formation of the unique β-lactone ring.