bluuebunny/crossref_metadata_2025 huggingface dataset:
Cronos Titin Is Expressed in Human Cardiomyocytes and Necessary for Normal Sarcomere Function
Authors: Zaunbrecher Rebecca J. , Abel Ashley N. , Beussman Kevin , Leonard Andrea , von Frieling-Salewsky Marion , Fields Paul A. , Pabon Lil , Reinecke Hans , Yang Xiulan , Macadangdang Jesse , Kim Deok-Ho , Linke Wolfgang A. , Sniadecki Nathan J. , Regnier Michael , Murry Charles E.
Published: October 2019

Background:

The giant sarcomere protein titin is important in both heart health and disease. Mutations in the gene encoding for titin (
TTN
) are the leading known cause of familial dilated cardiomyopathy. The uneven distribution of these mutations within
TTN
motivated us to seek a more complete understanding of this gene and the isoforms it encodes in cardiomyocyte (CM) sarcomere formation and function.

Methods:

To investigate the function of titin in human CMs, we used CRISPR/Cas9 to generate homozygous truncations in the Z disk (TTN-Z
−/−
) and A-band (TTN-A
−/−
) regions of the
TTN
gene in human induced pluripotent stem cells. The resulting CMs were characterized with immunostaining, engineered heart tissue mechanical measurements, and single-cell force and calcium measurements.

Results:

After differentiation, we were surprised to find that despite the more upstream mutation, TTN-Z
−/−
-CMs had sarcomeres and visibly contracted, whereas TTN-A
−/−
-CMs did not. We hypothesized that sarcomere formation was caused by the expression of a recently discovered isoform of titin, Cronos, which initiates downstream of the truncation in TTN-Z
−/−
-CMs. Using a custom Cronos antibody, we demonstrate that this isoform is expressed and integrated into myofibrils in human CMs. TTN-Z
−/−
-CMs exclusively express Cronos titin, but these cells produce lower contractile force and have perturbed myofibril bundling compared with controls expressing both full-length and Cronos titin. Cronos titin is highly expressed in human fetal cardiac tissue, and when knocked out in human induced pluripotent stem cell derived CMs, these cells exhibit reduced contractile force and myofibrillar disarray despite the presence of full-length titin.

Conclusions:

We demonstrate that Cronos titin is expressed in developing human CMs and is able to support partial sarcomere formation in the absence of full-length titin. Furthermore, Cronos titin is necessary for proper sarcomere function in human induced pluripotent stem cell derived CMs. Additional investigation is necessary to understand the molecular mechanisms of this novel isoform and how it contributes to human cardiac disease.
Concentration of Branched-Chain Amino Acids Is a Strong Risk Marker for Incident Hypertension
Authors: Flores-Guerrero Jose L. , Groothof Dion , Connelly Margery A. , Otvos James D. , Bakker Stephan J.L. , Dullaart Robin P.F.
Published: October 2019

The potential role of branched-chain amino acids (BCAAs) in the pathogenesis of cardiometabolic diseases is increasingly recognized, but the association of BCAAs with incident hypertension remains unknown. The aim of the present study was to explore the association of BCAAs with incident hypertension in a prospective population-based cohort study. We measured plasma concentrations of BCAAs by means of nuclear magnetic resonance spectroscopy in 4169 participants from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study. We estimated the risk of incident hypertension using multivariable-adjusted Cox regression models. After a median follow-up of 8.6 years, incident hypertension was ascertained in 924 subjects. Cox regression analyses revealed a significant association between BCAAs and incident hypertension. The hazard ratio per one SD of BCAAs was 1.11 (95% CI, 1.02–1.20;
P
=0.01) after full adjustment for multiple clinical variables. Likewise, the fully adjusted association remained significant when evaluated as categorical variable (hazard ratio for upper quartile with lowest quartile as reference category, 1.36; 95% CI, 1.11–1.68;
P
=0.003). Furthermore, the net reclassification improvement assessment improved after addition of BCAAs to a traditional risk model (
P
<0.001). This prospective study revealed that high plasma concentrations of BCAAs are associated with an increased risk of newly developed hypertension. The association remained after adjusting for age, sex, body mass index, and lipid profile.
Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Acute, Nonminor Stroke
Authors: Kim Joon-Tae , Park Man-Seok , Choi Kang-Ho , Cho Ki-Hyun , Kim Beom Joon , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae-Kwan , Kim Dae-Hyun , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Kim Dong-Eog , Ryu Wi-Sun , Choi Jay Chol , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Sohn Sung Il , Hong Jeong-Ho , Lee Ji Sung , Lee Juneyoung , Bae Hee-Joon
Published: October 2019

Background and Purpose—

This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel plus aspirin (DAPT) with that of aspirin monotherapy (AM) in patients with acute, nonminor, and noncardioembolic stroke.

Methods—

Using a prospective, nationwide, multicenter stroke registry database, acute (within 24 hours of onset), nonminor (baseline National Institutes of Health Stroke Scale score, 4–15), and noncardioembolic stroke patients were identified. Propensity scores using inverse probability of treatment weighting were used to adjust baseline imbalances between the DAPT and AM groups. A primary outcome measure was a composite of all types of stroke (ischemic and hemorrhagic), myocardial infarction, and all-cause mortality within 3 months of stroke onset.

Results—

Among the 4461 patients meeting the eligibility criteria (age, 69±13 years; men, 57.7%), 52.5% (n=2340) received AM, and 47.5% (n=2121) received DAPT. The primary outcome event was not significantly different between the DAPT group and the AM group (20.9% versus 22.6%,
P
=0.13). The event rates of all types of stroke were also not different between the 2 groups (19.3% versus 20.1%,
P
=0.35), while all-cause mortality was significantly lower in the DAPT group than in the AM group (3.4% versus 4.9%,
P
=0.02). In the propensity-weighted Cox proportional hazards models with robust estimation, DAPT did not reduce the risk of the primary outcome event (hazards ratio, 0.91; 95% CI, 0.79–1.04) but did reduce the risk of all-cause mortality (0.69; 0.49–0.97). There was no treatment heterogeneity among the predefined subgroups, although the potential benefits of DAPT were suggested in subpopulations of moderate-to-severe relevant arterial stenosis and relatively severe deficits (National Institutes of Health Stroke Scale score, 12–15).

Conclusions—

Compared to AM, clopidogrel plus aspirin did not reduce the risk of the primary outcome event during the first 3 months after a nonminor, noncardioembolic, ischemic stroke.
Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke
Authors: Torres-Aguila Nuria P. , Carrera Caty , Giese Anne-Katrine , Cullell Natalia , Muiño Elena , Cárcel-Márquez Jara , Gallego-Fabrega Cristina , González-Sánchez Jonathan , del Mar Freijo María , Álvarez-Sabín José , Molina Carlos , Ribó Marc , Jimenez-Conde Jordi , Roquer Jaume , Sobrino Tomás , Campos Francisco , Castillo José , Muñoz-Narbona Lucia , Lopez-Cancio Elena , Dàvalos Antoni , Diaz-Navarro Rosa , Tur Silvia , Vives-Bauza Cristòfol , Serrano-Heras Gemma , Segura Tomás , Krupinski Jerzy , Delgado-Mederos Raquel , Martí-Fàbregas Joan , Heitsch Laura , Ibañez Laura , Cruchaga Carlos , Rost Natalia S. , Montaner Joan , Lee Jin-Moo , Fernandez-Cadenas Israel
Published: October 2019

Background and Purpose—

Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke.

Methods—

Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed.

Results—

Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance (
P
<5×10
−8
). The 14q24.3 locus was associated with acute stroke outcome (rs112809786,
P
=0.036) and with
ACOT1
and
PTGR2
gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study.

Conclusions—

We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.
Dual Antiplatelet Therapy Increases Hemorrhagic Transformation Following Thrombolytic Treatment in Experimental Stroke
Authors: Zheng Yi , Lieschke Franziska , Schaefer Jan Hendrik , Wang Xiaoying , Foerch Christian , van Leyen Klaus
Published: October 2019

Background and Purpose—

Dual antiplatelet treatment poses a risk for increased hemorrhagic transformation (HT) following intravenous thrombolysis and mechanical thrombectomy. The aim of this study was to implement a model of experimental stroke with tissue-type plasminogen activator (tPA)-associated HT in mice on dual antiplatelet treatment to enable mechanistic studies and also to allow for an initial assessment of therapeutic approaches to limit HT.

Methods—

Male C57BL6 mice were fed with Aspirin and Clopidogrel via drinking water for 3 days. Subsequently, mice were subjected to 2-hour transient middle cerebral artery occlusion, and tPA was infused when indicated. HT was quantified by measuring hemorrhaged areas in brain sections with ImageJ. TTC staining was used to determine infarct size. Platelet function was tested in vitro using flow cytometry and in vivo with standard tail bleeding tests.

Results—

Both flow cytometry and tail bleeding volumes indicated significantly reduced platelet function following Aspirin and Clopidogrel treatment. While tPA administered 2 hours after onset of middle cerebral artery occlusion did not cause bleeding in control mice (0.51±0.13 mm2), HT significantly increased by 18.9±5.4 mm2 (
P
=0.0045) in Aspirin and Clopidogrel mice treated with tPA. HT in aspirin and clopidogrel mice not treated with tPA was nonsignificantly elevated by 8.0±4.6 mm
2
(
P
=0.3784) compared with controls. Infarct sizes did not differ between groups. The HT persisted when the tPA dosage was reduced.

Conclusions—

We successfully established a translational stroke model of tPA treatment under dual antiplatelet treatment. The impaired platelet function led to an increased risk for HT in tPA-treated mice. Reducing the dosage of tPA did not prevent this hemorrhagic complication.
Persea himalayensis (Lauraceae), a superfluous name for Machilus odoratissima and second-step lectotypification of Machilus odoratissima

Authors: KUMAR ANAND
Published: October 2019

The genus Machilus Nees von Esenbeck (1831: 70) comprises c. 100 species distributed in tropical and subtropical S and SE Asia (Wei & van der Werff 2008). Kostermans (1952: 116) transferred Machilus to Persea Miller (1754: without pagination), but recent molecular evidence supports that Machilus should be treated as a distinct genus (Rohwer et al. 2009, Li et al. 2011). The type species Machilus odoratissima Nees von Esenbeck (1831: 70) was described with two unnamed varieties α and β based on the collections no. 2607A–F of Wallich’s Catalogue. For variety α, Nees von Esenbeck stated ‘paniculis floribusque pubescentibus, baccis globosis’ and cited ‘n. 2607 A ex parte, C, D, E.’ For variety β, he stated ‘paniculis floribusque glabriusculis aut sparsim puberulis, baccis ovatis vel (immaturis) oblongis’ and cited ‘n. 2607 A ex parte, B, F’. Hooker (1890: 859–860) was the first person to clarify Nees’s original material. He noted that the collection no. 2607A of Wallich’s catalogue from Nepal was in bud only, and the panicles as well as the buds were silky pubescent. In his opinion, it was possibly a large leaved form of M. bombycina King ex Hooker (1890: 861).  In fact, the collection no. 2607A consists of several specimens deposited in different herbaria, bearing buds, flowers and fruits. The collections with silky pubescent buds (BM000888163, E00393305, E00393306, GZU000254236, K000821638, K000821637, K001116551, L0036904, L0036905, MEL2389976), pubescent flowers (GZU000254234) and globose fruits (GZU000254237) are of M. duthiei King ex Hook.f. (1890: 861) and the specimens with glabrous inflorescences (CAL0000073560, E00680973, K000228477, NY00355177, NY00355178) and oblong fruits (CAL0000073560, GZU000254235) are of M. odoratissima. Some fruits of M. odoratissima were wrongly placed in a packet attached to a specimen of M. duthiei bearing barcode no. GZU000254236. These fruits most likely have been taken from the specimen bearing barcode no. GZU000254235, which is of M. odoratissima. The collection no. 2607B from ‘Chercoolie’ in the ‘Deyra Dhoon’ (Dehra Dun) has a perfectly glabrous panicle, old flowers and oblong fruit. Hooker believed that this was what Wallich intended for M. odoratissima. He also stated that the collections from Rungpore and Patgong, no. 2607C, with globose small fruit, and perhaps (indicated by a question mark) the one from Goalpara, no. 2607D, were the cultivated M. bombycina. Hooker mentioned that the collection no. 2607E from Silhet, with a silky perianth and long glaucous leaves, was probably M. kurzii King ex Hooker (1890: 860) and the collection no. 2607F, supposedly from Singapore, was ‘unquestionably the same as B’, but the locality was almost certainly erroneous.
A new species of Archaebranchinecta (Anostraca: Branchinectidae) from the South American Altiplano
Authors: COHEN ROSA GRACIELA , MARINONE MARÍA CRISTINA , ADAMOWICZ SARAH J.
Published: October 2019

A detailed morphological comparison was carried out among specimens of several samples of Archaebranchinecta Rogers & Coronel, 2011 from the Altiplano of Peru, Bolivia, and Argentina. Surprisingly, striking differences were found between Peruvian samples collected near the western shore of Lake Titicaca, and those from Bolivia taken southwardly, near the east coasts of River Desaguadero and Lake Poopó. Accordingly, the new species Archaebranchinecta aimara sp. nov. is described, representing the second specific entity of a genus that so far included only A. pollicifera (Harding, 1940). The main differential features between both species include: (a) size and shape of the three processes of basal segment of the male second antenna; (b) shape and protrusion degree of the pair of medioventral bulges in the male genital segments; (c) presence or absence of strong ventrolateral spine on the second genital segment of female; and (d) presence or absence of a pair of ventrolateral outgrowths in the brood pouch. This research contributes to our understanding of the biodiversity and endemism of the unique Altiplano region of South America.
Recent Trends in the Near-Surface Climatology of the Northern North American Great Plains
Authors: Bromley Gabriel T. , Gerken Tobias , Prein Andreas F. , Stoy Paul C.
Published: October 2019

We examined climate trends in the northern North American Great Plains (NNAGP) from 1970 to 2015, a period that aligns with widespread land-use changes in this globally important agricultural region. Trends were calculated from the Climatic Research Unit (CRU) and other climate datasets using a linear regression model that accounts for temporal autocorrelation. The NNAGP warmed on an annual basis, with the largest change occurring in winter (DJF) at 0.4°C decade−1. January in particular warmed at nearly 0.9°C decade−1. The NNAGP cooled by −0.18°C decade−1 during May and June, nearly the opposite of global warming trends during the study period. The atmospheric vapor pressure deficit (VPD), which can limit crop growth, decreased in excess of −0.4 hPa decade−1 during climatological summer in the southeastern part of the study domain. Precipitation P increased in the eastern portion of the NNAGP during all seasons except fall and increased during May and June in excess of 8 mm decade−1. Climate trends in the NNAGP largely followed global trends except during the early warm season (May and June) during which 2-m air temperature Tair became cooler, VPD lower, and P greater across large parts of the study region. These changes are consistent with observed agricultural intensification during the study period, namely the reduction of summer fallow and expansion of agricultural land use. Global climate model simulations indicate that observed Tair trends cannot be explained by natural climate variability. However, further climate attribution experiments are necessary to understand if observed changes are caused by increased agricultural intensity or other factors.
Atmospheric Mixed Layer Convergence from Observed MJO Sea Surface Temperature Anomalies
Authors: de Szoeke Simon P. , Maloney Eric D.
Published: October 2019

The Madden–Julian oscillation (MJO) dominates tropical weather on intraseasonal 30–90-day time scales, yet mechanisms for its generation, maintenance, and propagation remain unclear. Although surface moist static energy (MSE) flux is greatest under strong winds in the convective phase, sea surface temperature (SST) warms by ~0.3°C in the clear nonconvective phase of the MJO. Winds converging into the hydrostatic low pressure under warm air over the warm SST increase the vertically integrated MSE. We estimate column-integrated MSE convergence using a model of mixed layer (ML) winds balancing friction, planetary rotation, and hydrostatic pressure gradients. Small (0.3 K) SST anomalies associated with the MJO drive 7 W m−2net column MSE convergence averaged over the equatorial Indian Ocean ahead of MJO deep convection. The MSE convergence is in the right phase to contribute to MJO generation and propagation. It is on the order of the total MSE tendency previously assessed from reanalysis, and greater than surface heat flux anomalies driven by intraseasonal SST fluctuations.
Influence of Bottom Topography on Vortex Stability
Authors: Zhao Bowen , Chieusse-Gérard Emma , Flierl Glenn
Published: October 2019

The effects of topography on the linear stability of both barotropic vortices and two-layer, baroclinic vortices are examined by considering cylindrical topography and vortices with stepwise relative vorticity profiles in the quasigeostrophic approximation. Four vortex configurations are considered, classified by the number of relative vorticity steps in the horizontal and the number of layers in the vertical: barotropic one-step vortex (Rankine vortex), barotropic two-step vortex, and their two-layer, baroclinic counterparts with the vorticity steps in the upper layer. In the barotropic calculation, the vortex is destabilized by topography having an oppositely signed potential vorticity jump while stabilized by topography of same-signed jump, that is, anticyclones are destabilized by seamounts while stabilized by depressions. Further, topography of appropriate sign and magnitude can excite a mode-1 instability for a two-step vortex, especially relevant for topographic encounters of an otherwise stable vortex. The baroclinic calculation is in general consistent with the barotropic calculation except that the growth rate weakens and, for a two-step vortex, becomes less sensitive to topography (sign and magnitude) as baroclinicity increases. The smaller growth rate for a baroclinic vortex is consistent with previous findings that vortices with sufficient baroclinic structure could cross the topography relatively easily. Nonlinear contour dynamics simulations are conducted to confirm the linear stability analysis and to describe the subsequent evolution.
Sustained relief of trigeminal neuropathic pain by a blood–brain barrier penetrable PPAR gamma agonist
Authors: Zhang Morgan , Hu Min , Montera Marena A , Westlund Karin N
Published: October 2019

The blood–brain barrier (BBB) and blood–nerve barrier ensure protection of the nervous system but pose a challenge for the treatment of pain since it restricts passage of many therapeutic drugs. Although it is unknown which blood–neural barrier is more relevant, or whether permeabilities are the same for different barriers, we proposed that the inefficiency of thiazolidinedione-type agonists for peroxisome proliferator-activated receptor gamma (PPARɣ) is due to their difficulty in passage through the BBB. We developed a new highly BBB penetrable PPARɣ agonist for the treatment of neuropathic pain, assuming BBB permeability is a rule of thumb to estimate the overall permeability of relevant blood–neural barriers.  As an index of brain penetration, the brain–plasma ratio (Kp) of ELB00824 is 5.13, suggesting very high brain bioavailability, which is 58-fold that of pioglitazone. The series of studies presented here indicate that ELB00824 may be the most potent PPARɣ agonist currently known for acute reduction of neuropathic pain in trigeminal nerve in rat and mouse models. Low-dose PPARɣ agonist, ELB00824 (10 mg/kg), effectively decreased neuropathic hypersensitivity in mice and rats at both acute and chronic time points, a dose 100-fold lower than the effective dose (1000 mg/kg, i.p.) of pioglitazone. Comparisons of ELB00824 alone or in combination with gabapentin or carbamazepine are provided. While PPARɣ agonists used to treat Type 2 diabetes produce several adverse side effects, sub-chronic oral toxicity study provided promising results that ELB00824 does not produce any significant short-term toxicity. The study animals of either sex remained alive and healthy with no significant alteration of body weight long term. Toxicity study results obtained were satisfactory, with no significant alterations in any serum biochemistry parameters.
AIKYATAN: mapping distal regulatory elements using convolutional learning on GPU
Authors: Fang Chih-Hao , Theera-Ampornpunt Nawanol , Roth Michael A. , Grama Ananth , Chaterji Somali
Published: October 2019

Background

The data deluge can leverage sophisticated ML techniques for functionally annotating the regulatory non-coding genome. The challenge lies in selecting the appropriate classifier for the specific functional annotation problem, within the bounds of the hardware constraints and the model’s complexity. In our systemAikyatan, we annotate distal epigenomic regulatory sites, e.g., enhancers. Specifically, we develop a binary classifier that classifies genome sequences as distal regulatory regions or not, given their histone modifications’ combinatorial signatures. This problem is challenging because the regulatory regions are distal to the genes, with diverse signatures across classes (e.g., enhancers and insulators) and even within each class (e.g., different enhancer sub-classes).

Results

We develop a suite of ML models, under the bannerAikyatan, including SVM models, random forest variants, and deep learning architectures, for distal regulatory element (DRE) detection. We demonstrate, with strong empirical evidence, deep learning approaches have a computational advantage. Plus, convolutional neural networks (CNN) provide the best-in-class accuracy, superior to the vanilla variant. With the human embryonic cell line H1, CNN achieves an accuracy of 97.9% and an order of magnitude lower runtime than the kernel SVM. Running on a GPU, the training time is sped up 21x and 30x (over CPU) for DNN and CNN, respectively. Finally, our CNN model enjoys superior prediction performance vis-‘a-vis the competition. Specifically,Aikyatan-CNN achieved 40% higher validation rate versus CSIANN and the same accuracy as RFECS.

Conclusions

Our exhaustive experiments using an array of ML tools validate the need for a model that is not only expressive but can scale with increasing data volumes and diversity. In addition, a subset of these datasets have image-like properties and benefit from spatial pooling of features. OurAikyatansuite leverages diverse epigenomic datasets that can then be modeled using CNNs with optimized activation and pooling functions. The goal is to capture the salient features of the integrated epigenomic datasets for deciphering the distal (non-coding) regulatory elements, which have been found to be associated with functional variants. Our source code will be made publicly available at:https://bitbucket.org/cellsandmachines/aikyatan.
Prevalence of first-degree atrioventricular block and the associated risk factors: a cross-sectional study in rural Northeast China
Authors: Du Zhi , Xing Liying , Lin Min , Tian Yuanmeng , Jing Li , Yan Han , Zhang Boqiang , Liu Shuang , Yu Shiwen , Sun Yingxian
Published: October 2019

Background

First-degree atrioventricular block (AVB) has traditionally been regarded as a benign condition but recent studies have challenged this conception. Prevalence of 1–2% have been reported in developed countries in Asia. However, no epidemiologic studies have established the prevalence of first-degree AVB in developing countries. The aim of the study was to investigate the prevalence of first-degree AVB in rural northeast China and identify the associated risk factors.

Methods

This cross-sectional study was undertaken from September 2017 to May 2018 in rural areas of Liaoning Province. It involved 10,926 participants aged ≥40 years (85.3% of those who were eligible). First-degree AVB was confirmed by at least two independent cardiologists. Risk factors were evaluated using stepwise logistic regression.

Results

The prevalence of first-degree AVB was 3.4% (95% confidence interval [CI]: 3.0–3.8%). Males had a higher prevalence than females (5.1% vs. 2.2%, p < 0.001). The regression model involving all participants showed that age (odds ratio [OR]: 1.32; p <0.001), male sex (OR: 1.72; p = 0.001), height (OR: 1.25; p = 0.008), systolic blood pressure (SBP) (OR: 1.15; p = 0.003), triglycerides (TG) (OR: 1.10; p < 0.001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.73; p < 0.001), heart rate (OR: 0.78; p < 0.001), and exercising regularly (OR: 0.73; p = 0.030) were independent risk factors.

Conclusions

First-degree AVB is highly prevalent in rural areas of northeast China. The associated independent risk factors include being male, older, and taller, higher SBP and TG, lower HDL-C and heart rate, and lack of exercise.
Braden scale for assessing pneumonia after acute ischaemic stroke
Authors: Ding Yunlong , Yan Yazhou , Niu Jiali , Zhang Yanrong , Gu Zhiqun , Tang Ping , Liu Yan
Published: October 2019

Background

The prevention of pneumonia is critical for patients with acute ischaemic stroke (AIS). The six subscales in the Braden Scale seem to be related to the occurrence of pneumonia. We aimed to evaluate the feasibility of using the Braden Scale to predict the occurrence of pneumonia after AIS.

Methods

We studied a series of consecutive patients with AIS who were admitted to the hospital. The cohort was subdivided into pneumonia and no pneumonia groups. The scores on the Braden Scale, demographic characteristics and clinical characteristics were obtained and analysed by statistical comparisons between the two groups. We investigated the predictive validity of the Braden Scale by receiver operating characteristic (ROC) curve analysis.

Results

A total of 414 patients with AIS were included in this study. Of those 414 patients, 57 (13.8%) patients fulfilled the criteria for post-stroke pneumonia. There were significant differences in age and histories of chronic obstructive pulmonary disease (COPD), dysphagia and Glasgow Coma Scale (GCS) score between the two groups, and the National Institutes of Health Stroke Scale (NIHSS) score in the pneumonia group was significantly higher than that in the no pneumonia group (P < 0.01). The mean score on the Braden Scale in the pneumonia group was significantly lower than that in the no pneumonia group (P < 0.01). The six subscale scores on the Braden Scale were all significantly different between the two groups. The area under the curve (AUC) for the Braden Scale for the prediction of pneumonia after AIS was 0.883 (95% CI = 0.828–0.937). With 18 points as the cutoff point, the sensitivity was 83.2%, and the specificity was 84.2%.

Conclusion

The Braden Scale with 18 points as the cutoff point is likely a valid clinical grading scale for predicting pneumonia after AIS at presentation. Further studies on the association of the Braden Scale score with stroke outcomes are needed.
Multiple sequence types responsible for healthcare-associated Acinetobacter baumannii dissemination in a single centre in Egypt
Authors: Al-Hassan Leena , Zafer Mai M. , El-Mahallawy Hadir
Published: October 2019

Background

Acinetobacter baumannii is an increasingly worrying organism in the healthcare setting, due to its multidrug resistance and persistence. Prolonged hospitalisation, immunocompromised patients and excessive antibiotic exposure all contribute to increasing the risk of A. baumannii infections, which makes cancer patients a significant risk group. This study aims to investigate the dissemination of A. baumannii at the National Cancer Institute (NCI) in Cairo – Egypt.

Methods

All bacterial isolates were typed using Multi-locus Sequence Typing (MLST) to characterise the epidemiology of isolates. The intrinsic OXA-51-like, and the acquired carbapanemases OXA-23, − 24/40, − 58, NDM, IMP, and VIM were also amplified and sequenced to genetically identify mechanisms of carbapenem resistance.

Results

MLST results show a high degree of multi-clonal dissemination, with 18 different Sequence Types (STs) identified, including 5 novel. The majority of isolates belonged to International Clone (IC) 2, and carbapenem resistance was detected in 93% of isolates and mediated by blaOXA-23, blaOXA-58, blaNDM-1 and blaVIM-1. We also report the presence of a resistant ST732 (OXA-378) which has been previously identified in migratory birds.

Conclusions

Multiple highly resistant clones were identified in a Cancer hospital in Cairo. It is vital that clinicians and healthcare workers are aware of the population of A. baumannii present in order to have appropriate treatment and infection control practices.
Past history of stage I/II solid tumor malignancy impacts considerably on sepsis mortality: a propensity score matching analysis from the hellenic sepsis study group
Authors:   on behalf of the Hellenic Sepsis Study Group, Dimοpoulos George , Rovina Nikoletta , Patrani Maria , Antoniadou Eleni , Konstantonis Dimitrios , Vryza Konstantina , Vlachogianni Glykeria , Kyprianou Miltiades , Routsi Christina , Giamarellos-Bourboulis Evangelos J.
Published: October 2019

Background

Whether past history of solid stage I/II inactive cancer has an impact on 28-day mortality of sepsis remains unclear. We aimed to determine the impact of history of stage I or II solid tumor malignancy in complete remission the last 3 years on sepsis outcome.

Methods

Using the database of the Hellenic Sepsis Study Group from 1553 patients with sepsis admitted in the ICU, 83 patients with sepsis by Sepsis-3 definition with past-history of stage I/II inactive solid malignancy the last 3 years were depicted. A comparator group of 83 patients fully matched for age, severity, type of infection and comorbidities was selected by propensity score matching.

Results

Mortality after 28 days was 37.3% in the comparator group and 54.2% in the solid tumor stage I/II group (odds ratio for death 1.98; p: 0.030). Following step-wise forward Cox regression analysis, septic shock (hazard ratio 1.80), acute renal injury (hazard ratio 2.06), history of coronary heart disease (hazard ratio 0.36) and history of stage I/II solid tumor malignancy (hazard ratio 1.79) were the only independent variables associated with 28-day mortality. Serum levels of procalcitonin and of soluble urokinase plasminogen activator receptor were similar between the two groups of comparisons.

Conclusions

Past history of stage I/II solid malignancy is an independent risk factor for unfavorable outcome from sepsis the first 28 days.
Adiponectin levels in maternal serum and umbilical cord blood at birth by mode of delivery: relationship to anthropometric measurements and fetal sex
Authors: Fazeli Daryasari Seyedeh Razieh , Tehranian Najmeh , Kazemnejad Anoshirvan , Razavinia Fatemeh , Tork Tatari Fatemeh , Pahlavan Fattaneh
Published: October 2019

Background

The rate of cesarean section is increasing worldwide. Adiponectin is a hormone related to anti-inflammatory and anti-atherogenic effects; and it′s concentrations may change in response to inflammatory situations including surgical intervention. The aim of the current study was to investigate serum adiponectin levels in maternal and umbilical cord blood according to different modes of delivery and their relationship with anthropometric measurements and fetal sex.

Methods

The study population initially comprised 90 healthy pregnant women referred to the teaching hospital. Eventually, 40 participants in the vaginal delivery group and 35 subjects in the cesarean delivery group were recruited in to the study. Umbilical cord blood and maternal serum samples were analyzed according to the standard protocol from the manufacturer. The collected data were analyzed using SPSS-16 software. P-value < 0.05 was considered as the significance level for all tests.

Results

Our results indicated a significant association between maternal adiponectin and the mode of delivery, with adiponectin levels significantly higher in vaginal delivery compared to cesarean section (P < 0.001). However, no difference was found in umbilical cord blood adiponectin between the two groups (P = 0.51). A significant positive correlation was found between maternal serum adiponectin in the first day after birth and umbilical cord blood adiponectin in the vaginal delivery group (P = 0.007). Nevertheless, this correlation was not statistically significant in the cesarean delivery group (P = 0.62). There was also no significant correlation between fetal sex and anthropometric measurements with maternal adiponectin (P = 0.44) and umbilical cord blood adiponectin (P = 0.86).

Conclusions

The result of the current study revealed that maternal adiponectin concentration was significantly higher in vaginal delivery compared to cesarean section, which might be due to the increased levels of maternal adiponectin release during labor.
The effects of photodynamic therapy on leukemia cells mediated by KillerRed, a genetically encoded fluorescent protein photosensitizer
Authors: Yuan Meng , Liu Chengcheng , Li Jiao , Ma Wenpeng , Yu Xiaozhuo , Zhang Ping , Ji Yanhong
Published: October 2019

Background

Leukemia is a cancer of blood and bone marrow cells, causing about 300,000 deaths worldwide. Photodynamic therapy (PDT) is a promising alternative for the treatment of malignant tumors. KillerRed is a genetically encoded red fluorescent protein photosensitizer (PS). In this study, we aimed to investigate the effects of KillerRed-mediated PDT on chronic myelogenous leukemia K562 cells, acute monocytic leukemia NB4 cells, and acute monocytic leukemia THP1 cells.

Methods

KillerRed was expressed inEscherichia colicells, purified by Q-Sepharose column, and confirmed by western-blotting. The PDT effect on cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PE Annexin V/7-AAD staining and flow cytometry. The distribution of KillerRed in leukemia cells was detected by confocal laser scanning microscopy (CLSM) and western-blotting. The ROS generation was measured by flow cytometry.

Results

Pure KillerRed was obtained with a yield of about 37 mg per liter of bacterial cells. KillerRed photodynamic inactivated the leukemia cells in a concentration-dependent manner, but exhibited no obvious dark toxicity. PDT mediated by KillerRed could also induce apoptotic response (mainly early apoptosis) in the three cell lines. The CLSM imaging indicated that KillerRed was distributed within the cytoplasm and nuclei of leukemia cells, causing damages to the cytoplasm and leaving the nuclear envelope intact during light irradiation. KillerRed distributed both in the cytosol and nuclei was confirmed by western blotting, and ROS significantly increased in PDT treated cells compared to the cells treated with KillerRed alone.

Conclusions

Our studies demonstrated that KillerRed-mediated PDT could effectively inactivate K562, NB4, and THP1 leukemia cells and trigger cell apoptosis, and it has potential to be used individually or complementally, in the treatment of leukemia.
Adherence and barriers to penile rehabilitation over 2 years following radical prostatectomy
Authors: Albaugh Jeffrey , Adamic Brittany , Chang Cecilia , Kirwen Nicholas , Aizen Joshua
Published: October 2019

Background

A variety of penile rehabilitation (PR) therapies are available to improve post-prostatectomy erectile dysfunction (ED) with mixed results. It is uncertain how adherent men are to PR therapies. The aim of this study is to determine adherence to and identify barriers to PR treatment.

Methods

A longitudinal cross-sectional approach was used in men who underwent radical prostatectomy over 2 years. Men were instructed to take a PDE5 inhibitor (PDE5i) three times per week, and if required, utilize a vacuum constriction device (VCD) daily. Outcomes were measured by multiple validated questionnaires. In addition, penile stretched length, side effects, compliance to PR regimen & barriers to participation were documented.

Results

Seventy-seven patients were enrolled, however only 49 completed evaluation at 3 or more timepoints and were included in analysis. This cohort was an average age of 58.1 years (±7.7), had robotic laparoscopic radical prostatectomy (91.7%), and had bilateral nerve sparing procedures (95.8%). Majority (62.5%) reported normal SHIM pre-operatively, however 79% used PDE5i. Erectile function as measured by IIEF and Erection Hardness Rating were negatively affected post-operatively, with gradual improvement in parameters throughout the 24 month follow up. Of the participants who had normal pre-op SHIM, only 23.1 and 28.6% regained baseline function at 1 and 2 years, respectively. Orgasm was significantly diminished immediately post-operatively, however, at the end of the study period only 37% of men reported diminished climax and no men reported absent orgasm. Adherence to penile rehabilitation therapies declined overtime. Men took oral PDE5i on average 2.3 times weekly at 12 and 24 months (p < 0.001). Men used the VCD 2.3–3.9 days a week, which declined overtime (p = 0.014).

Conclusions

Improvement in erectile and orgasm parameters was observed over time, but most men did not return to baseline function. Despite comprehensive instructions and a frequent follow up schedule, PDE5i and VCD adherence was poor. High attrition rates were noted with only 55.8% of men remaining at 12 months and 45% of men completing 24 months. The most common barriers to PR adherence were cost, inconvenience and perceived ineffectiveness.
A comparative study of the microtensile bond strength and microstructural differences between sclerotic and Normal dentine after surface pretreatment
Authors: Wang Jinhua , Song Weijian , Zhu Lei , Wei Xin
Published: October 2019

Background

The resin bond strength of sclerotic dentine is significantly lower than that of the normal dentine, which paused a challenge for bonding procedures clinically. The aim of this study was to compare the effects of different surface pretreatments on the micro-tensile bond strength and microstructure between sclerotic dentine and normal dentine.

Methods

Eighty teeth that were collected, forty premolars with typical wedge-shaped defects visually graded as class III were assigned as the sclerotic dentine group (SD), the other forty normal premolars with artificial wedge-shaped defects were assigned as the normal dentine group (ND). Each group was randomly subdivided into eight subgroups according to the solution used: 35% phosphoric acid, 15% EDTA, 5% or 10% NaClO. Then the dentine surface was examined using a scanning electron microscope (SEM). The lesions were restored using self-etching adhesive and the subsequent resin composite. The teeth were sectioned into sticks for the micro-tensile bond strength analysis, and the data were analysed using the SPSS17.0 software package (α = 0.05).

Results

First, for the ND groups, after pretreatment using 35% phosphoric acid, and 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the normal dentine were higher than that of the other groups (P < 0.05). Second, for the SD groups, after pretreatment using 35% phosphoric acid, 15% EDTA, and 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the sclerotic dentine were higher than that of the other groups (P < 0.05). Third, the bond strengths of the sclerotic dentine were lower than that of the normal dentine without any pretreatment (P < 0.05). After pretreatment using 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the sclerotic dentine were higher than that of the normal dentine (P < 0.05). SEM observation showed that the appearances of dentine surface were changed after pretreatment using the above solutions, with the reduced smear layer, opened small groove and increased dentinal tubules.

Conclusion

Pretreatment of dentine using 35% phosphoric acid+ 5% or + 10% sodium hypochlorite changed the microstructure of the sclerotic dentine surface and subsequently increased the micro-tensile bond strength.
Music in palliative care: a qualitative study with patients suffering from cancer
Authors: Pommeret Sandrine , Chrusciel Jan , Verlaine Catherine , Filbet Marilene , Tricou Colombe , Sanchez Stephane , Hannetel Louise
Published: October 2019

Background

The palliative care unit is an emotionally challenging place where patients and their families may feel at loss. Art can allow the expression of complex feelings. We aimed to examine how cancer patients hospitalized in the palliative care unit experienced a musical intervention.

Methods

We conducted a qualitative study based on semi-structured interviews. The study took place in a palliative care unit from 18 January 2017 to 17 May 2017. Two artists performed in the palliative care unit once a week from 9:30 am to 5:30 pm. The data from patient interviews were analysed based on an inductive approach to the verbatim accounts.

Results

The accounts we gathered led us to weigh the positive emotions engendered by this musical intervention against the potential difficulties encountered. The artists opened a parenthesis in the care process and brought joy and well-being to the palliative care unit. Patients also encountered difficulties during the intervention: reference to an altered general state, to loss of autonomy; a sense of the effort required, of fatigue; an adaptation period; reference to the end of life, to death; a difficulty in choosing songs.

Conclusions

Although music appeared to benefit the patients, it sometimes reminded them of their altered state. The difficulties experienced by patients during the experience were also related to physical exhaustion. Additional studies are needed to determine the benefits of music for patients and their families in the palliative care unit.
Number of parity is associated with low-grade albuminuria in middle-aged and elderly Chinese women
Authors: Sun Kan , Lin Diaozhu , Qiling Feng , Li Feng , Qi Yiqin , Feng Wanting , Ren Meng , Yan Li , Liu Dan
Published: October 2019

Background

Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria.

Methods

We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria.

Results

Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09–1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older.

Conclusion

Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.
Meta-analysis of vitamin D and lung function in patients with asthma
Authors: Liu Jian , Dong Yong-Quan , Yin Jie , Yao Jian , Shen Jie , Sheng Guo-Jie , Li Kun , Lv Hai-Feng , Fang Xing , Wu Wei-Fang
Published: October 2019

Background

There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients.

Methods

Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5.

Results

This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = − 0.1, 95% CI = − 0.11 to − 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = − 10.02, 95% CI = − 11 to − 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults.

Conclusions

Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.