bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS PENGARUH CAPITAL/LABOUR INTENSIVE, INVESTASI, KEPEMILIKAN MANAJERIAL, LEVERAGE OPERASI DENGAN VARIABEL MEDIASI KEBIJAKAN DIVIDEN DAN LEVERAGE KEUANGAN TERHADAP NILAI PERUSAHAAN
Authors: Nugraha Robi
Published: February 2019

ABSTRACT

The purpose of this study was to analyze the influence of capital labour intensive, investment, managerial ownership, operating leverage, dividen and financial leverage on the firm value of Indonesia non financial sector companies, the influence of capital labour intensive, investment, managerial ownership, operating leverage variable on dividen and financial leverage of Indonesia non financial sector companies, and the influence of capital labour intensive, investment, managerial ownership, operating leverage variable on the firm value through dividen and financial leverage as intervening variable.

The research data was collected using purposive sampling method to the data of non financial sector companies listed on the Indonesian Stock Exchange during the period 2003-2012. Based on the criteria of the study obtained 310 samples were then analyzed Using the panel data regression and path analysis. The results show that the capital labour intensive, investment, managerial ownership, operating leverage, dividen and financial leverage have significant influences on the firm value of Indonesia non financial sector companies. The capital labour intensive, investment, managerial ownership, operating leverage variable do not have significant influences on dividen. The capital labour intensive, investment, managerial ownership, operating leverage variable have significant influences on financial leverage.

With path analysis, the result show the The capital labour intensive, investment, managerial ownership, operating leverage variable do not have significant influence on the firm value of Indonesia non financial sector companies with dividen and financial leverage as intervening variable.

Keywords: Capital Labour Intensive, Investment, Managerial Ownership, Operating Leverage, Dividen and Financial Leverage, Firm Value.
Pengaruh Service Quality, Customer Satisfaction, dan Brand Trust di Mediasi Oleh Customer Commitment Terhadap Customer Loyalty Penumpang Maskapai Low Cost Carrier Di Bali
Authors: Lakhsmidevy Dewa ayu alit
Published: February 2019

Kebutuhan masyarakat Indonesia atas layanan transportasi terus meningkat sesuai dengan meningkatnya pembangunan nasional. Jenis layanan transportasi udara juga terus berkembang, salah satu adalah dengan beroperasinya model penerbangan unik yaitu melalui strategi penurunan operating cost di semua lini yang mengakibatkan harga tiket dapat ditekan. Model penerbangan ini disebut low cost carrier (LCC). Kepuasan konsumen terhadap pelayanan yang diberikan oleh maskapai penerbangan di Indonesia sangat berpengaruh terhadap seberapa besar tingkat kualitas pelayanan dari sebuah maskapai penerbangan. Berbagai pelayanan yang mempengaruhi, kepuasan konsumen adalah keramahan seluruh awak kabin, fasilitas fisik yang ada, tarif penerbangan, ketepatan waktu keberangkatan kemudahan akses dan juga keselamatan penerbangan. Berdasarkan jajak pendapat dari 2.674 orang responden mengenai apa yang diinginkan dari sebuah maskapai penerbangan didapatkan hasil sebanyak 9,6% menginginkan pelayanan ramah dari awak kabin, 16,9% penerbangan yang tepat waktu, armada yang baru 18,3%, 55,2% tarif yang murah (Indopos. 2015). Maskapai penerbangan di Indonesia sering mengalami keterlambatan waktu pada saat akan terbang atau dengan kata lain sering mengalami delay. Salah satu maskapai penerbangan di Indonesia yang sering mengalami keterlambatan dalam pemberangkatan pesawat adalah penerbangan low cost carriers. Secara garis besar tujuan penelitian ini adalah : menguji pengaruh service quality, customer satisfaction, brand trust terhadap costumer commitment serta dampaknya kepada customer loyalty pada penerbangan domestik maskapai low cost carrier di Bandara Internasional Ngurah Rai, Bali. Dengan unit observasi sebanyak 250 responden yang terdiri dari beberapa kriteria responden. Metode penelitian adalah explanatory survey. Hasil pengujian menunjukkan total indirect effect paling tinggi adalah pengaruh service quality terhadap customer loyalty dengan nilai t value sebesar 4,074, selanjutnya service quality terhadap customer commitment dengan nilai t value sebesar 3,243 di ikuti dengan sisa variabel lainnya. Hasil ini menunjukkan bahwa service quality merupakan variabel yang mendominasi pada hasil penelitian yang dilakukan. Semakin baik service quality yang diberikan maskapai kepada penumpang maka akan meninggkatkan komitmen penumpang dan selanjutnya akan menggiring penumapng untuk semakin loyal kepada maskapai.
Penerapan Customer Relationship Management (Crm) Dengan Menggunakan Metode Lrfm Analysis
Authors: Lubis Nurdin
Published: February 2019

Masyarakat Ekonomi ASEAN (MEA) atau ASEAN Economic Community telah dibuka. hal ini tak hanya membuka peluang, namun menjadi tantangan pula bagi sektor industri, termasuk industri farmasi nasional. Peningkatan kemampuan industri farmasi nasional dapat dilakukan melalui riset dan peningkatan kemampuanPenelitian ini dilakukan untuk mengetahui informasi mengenai karakteristik pelanggan dari PT Phapros Tbk, sebuah perusahaan yang bergerak pada bidang farmasi. Data yang digunakan yakni data pelanggan dan data transaksi penjualan historikal. Data tersebut kemudian akan diolah dengan LRFM model (Length, Recency, Frequency, Monetary), dan dua tahapan clustering (two stage clustering) yaitu metode wardâ€™s untuk mengetahui jumlah cluster terbaik dan algoritma k-means yang merupakan distance-based cluster analysis untuk melakukan proses operasional clustering. Setelah proses operasional clustering dilakukan, hasil cluster akan dipetakan dengan customer value matrix dan customer loyalty matrix untuk mengetahui karakteristik tiap segmen pelanggan.Hasil yang didapatkan dari studi kasus PT Phapros Tbk menunjukkan bahwa segmen atau grup pelanggan yang terbentuk semuanya memiliki perbedaan statistik yang signifikan, dan dapat dijelaskan dalam konteks strategi marketing. Oleh karena itu, penelitian ini berguna untuk menentukan strategi pengelolaan pelanggan tiap segmen.Key Words: Clustering Analysis, Customer Relationship Management, Data mining, LRFM model.
HASTANELERDE BİLGİ GÜVENLİĞİ YÖNETİMİ: NİTEL BİR ARAŞTIRMA
Authors: Baran Selma , Şener Emine
Published: February 2019

Bilgi güvenliği son yıllarda sağlık kurumlarında daha da önem kazanmaya başlamıştır. Özellikle teknolojik gelişmeler ile birlikte gerekli önlemler alınmadığı takdirde bilgi sızıntılarının artacağı düşünülmektedir. Hastane bilgi güvenliğine ilişkin çalışanların görüş, öneri ve değerlendirmelerini tespit etmek amacıyla nitel araştırma yönetmelerinden derinlemesine görüşmenin kullanıldığı bu çalışmada farklı birimlerde çalışan 12 hastane çalışanına ulaşılmıştır. Görüşmelerden elde edilen veriler ATLAS.ti nitel veri programında analiz edilerek yorumlanmıştır. Bu doğrultuda uygulamada ortaya çıkan sorunlar ve çözüm önerileri bu görüşler doğrultusunda oluşturulmuştur. Araştırma sonucunda, katılımcıların yaygın olarak bilgi güvenliğinin önemini vurguladıkları ve bilgi güvenliği olgusunun “hasta mahremiyeti” olgusuyla birlikte algılandığı tespit edilmiştir. Bunun yanı sıra fiziksel koşulların, gizlilik, bütünlük ve erişilebilirlik açısından bilgi güvenliği için gerekli olduğu görülmüştür. Bilgi güvenliği yönetim sisteminin etkili işlemesi amacıyla, yöneticiler ve çalışanların işbirliği içinde olması araştırma sonuçlarına ilişkin geliştirilen önerilerden biridir.
A randomized controlled trial of the effect of supervised progressive crosscontinuum strength training in older medical patients: the STAND-Cph trial
Authors: Pedersen Mette Merete , Petersen Janne , Beyer Nina , Juul-Larsen Helle Gybel , Jensen Pia Søe , Andersen Ove , Bandholm Thomas
Published: February 2019

Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and 4 weeks at home after discharge on change in mobility in older medical patients.
Methods: Older medical patients (≥65 yrs) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3 days/week for 4 weeks after discharge. The primary outcome was between-group difference in change in mobility from baseline to 4 weeks after discharge assessed by the De Morton Mobility Index. Secondary outcomes were 24-hour mobility, lower extremity strength, gait speed, grip strength and Activities of Daily Living.
Results: Eighty-five patients were randomized to the intervention (N=43) or control group (N=42). In the intervention group, 43% were highly compliant with the intervention. Our intention to treat analysis revealed no between-group difference in mobility (difference baseline to 4 weeks: -4.17 (IQR -11.09;2.74; p=0.24) nor in any of the secondary outcomes. The per protocol analysis showed that the intervention group increased significantly more in the daily number of steps taken compared to the control group (difference in change from baseline to 4 weeks: 1024.7 steps (IQR 0.7;2048.6); p<0.05; adjusted for mobility at baseline).
Conclusions: Simple supervised strength training for the lower extremities, combined with protein supplementation initiated during hospitalization and continued at home for 4 weeks after discharge was not superior to usual care on change in mobility at 4 weeks in older medical patients. For the secondary outcome, daily number of steps, high compliance with the intervention resulted in a higher daily number of steps. Less than half of the patients were compliant with the intervention indicating that a simpler intervention might be needed.
Trial registration: NCT01964482, https://clinicaltrials.gov/ct2/show/NCT01964482, registration date: October 14, 2013, trial protocol: PubMed ID (PMID): 27039381.
1-1-8 one-step sevoflurane-nitrous oxide wash-in scheme for low-flow anesthesia: simple, rapid, and predictable induction
Authors: Tribuddharat Sirirat , Sathitkarnmanee Thepakorn , Vattanasiriporn Naruemon , Thananun Maneerat , Nonlhaopol Duangthida , Somdee Wilawan
Published: February 2019

Background

Sevoflurane is suitable for low-flow anesthesia (LFA). LFA needs a wash-in phase. The reported sevoflurane wash-in schemes lack simplicity, target coverage, and applicability. We proposed a one-step 1-1-8 wash-in scheme for sevoflurane-nitrous oxide (N2O) LFA. The objective of our study was to identify times to achieve every alveolar concentration of sevoflurane (FAS) from 1% to 3.5%.

Methods

We recruited 102 adults requiring general anesthesia with endotracheal intubation and controlled ventilation. After induction and intubation, a wash-in was started using a fresh gas flow of oxygen (O2):N2O at 1:1 L·min-1 plus sevoflurane 8%. The ventilation was controlled to maintain end-tidal carbon dioxide (CO2) of 30-35 mmHg.

Results

The rising patterns of FAS and inspired concentration of sevoflurane (FIS) are similar and parallel. The FAS/FIS ratio increased from 0.46 to 0.72 within 260 sec. The respective times to achieve FAS of 1%, 1.5%, 2%, 2.5%, 3% and 3.5% were 1, 1.5, 2, 3, 3.5, and 4.5 min. The heart rate and blood pressure significantly increased initially then gradually decreased as FAS increased.

Conclusions

The 1-1-8 wash-in scheme for sevoflurane has many advantages, including simplicity, coverage, swiftness, safety, and economy. A respective FAS of 1%, 1.5%, 2%, 2.5%, 3%, and 3.5% can be expected at 1, 1.5, 2, 3, 3.5, and 4.5 min. This scheme may be applied for LFA in the situation where anesthetic gas analyzer is not available.
The effect of oxygenation by continuous low-pressure oxygen flow through thyrocricocentesis cannulation on asphyxia-induced injury in canine.
Authors: Huang Fengyi , Chen Feng , Zheng Xiaochun , Gao Fei
Published: February 2019

Background

To observe the oxygenation efficacy using a continuous low-pressure oxygen flow through thyrocricoid emergency airway by venous catheter needle in canine model of asphyxia.

Methods

Eighteen healthy male canine were randomly assigned to three group A (control), group B (continuous low-pressure oxygen flow insufflation), and group C (continuous low-pressure oxygen flow insufflation with chest compressions). After thyrocricocentesis cannulation and intubation achieved, ventilation was stopped for 40 minutes to establish asphyxia model. Electrocardiogram (ECG), arterial blood pressure (ABP), oxygen saturation (SpO2), heart rate (HR), arterial blood gas analysis was recorded in duration. Concentration of S100β protein, cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB) and moisture in brain tissue were measured at before asphyxia, 2h and 4h after resuscitation.

Results

Compared with the control group, the pace of decline in SpO2, PaO2, pH value and the raise of PaCO2, LAC were slower in the other two groups. Similarly, a delay in increase of concentration of S100β, cTnI was observed, moreover, cerebral edema in group B and group C was significantly alleviated. Compared with Group B, the level of serum S100β, cTnI and brain tissue moisture content was lower in Group C (p<0.05).

Conclusions

The implication of continuous low-pressure oxygen insufflation through venous catheter needle after thyrocricoid puncture with assisted chest compression can ameliorate oxygenation in vivo, slow the increasing of PaCO2 and reduce the accumulation of H+. Consequently, it could attenuate the injury of vital organs, and finally improve prognosis. So it can be a promising approach for rescuing patients with asphyxia in clinic.
Conversion to Mechanical Pruning in Vineyards Maintains Fruit Composition while Reducing Labor Costs in ‘Merlot’ Grape Production
Authors: Kurtural S. Kaan , Beebe Andrew E. , Martínez-Lüscher Johann , Zhuang Shijian , Lund Karl T. , McGourty Glenn , Bettiga Larry J.
Published: February 2019

A field study was conducted for three consecutive seasons in the hot climate of central California to assess the performance of ‘Merlot’ grapevine (Vitis vinifera) grafted onto ‘Freedom’ [Fresno 1613-59 × Dog Ridge 5 (27% V. vinifera hybrid)] during training system conversion to facilitate mechanization. The traditional head-trained and cane-pruned (CP) system was either retained or converted either to a bilateral cordon-trained, spur-pruned California sprawl training system (HP), or to a bilateral cordon-trained, mechanically box-pruned single high-wire sprawling system (SHMP). After the conversion, SHMP sustained greater yield with more clusters per vine and smaller berries without affecting the canopy microclimate. This was due to a higher number of nodes retained after dormant pruning. The SHMP canopies, compared with CP and HP; filled allotted canopy space earlier based on photosynthetically active radiation (PAR) transmitted through the canopies, populating the space allotted per vine, favoring higher production efficiency. There were no adverse effects of training systems on berry composition or flavonoid concentration, during or after conversion to mechanical management. However, experimental year effect was obvious on anthocyanin composition of ‘Merlot’ berries, increasing trihydroxylated (i.e., delphinidin-based) anthocyanins in the latter years of the experiment. Our results also provided evidence that earlier canopy growth coupled with sufficient reproductive compensating responses allowed for increased yields while reaching commercial maturity without a decline in anthocyanin content with the SHMP. Converting CP to SHMP reduced labor operations costs by 90%. Furthermore, the SHMP had greater gross revenue and resulted in greater net income per acre even when the conversion year was taken into account. Therefore, SHMP is recommended for growers within the hot climate of the central San Joaquin Valley as a means to maintain productivity of vineyards while not sacrificing berry composition at the farm gate.
Postoperative Care of the Patient With Pulmonary Hypertension
Authors: Dezube Rebecca , Housten Traci , Mathai Stephen C.
Published: February 2019

CASE: SH is a 46-year-old woman with idiopathic pulmonary arterial hypertension (IPAH) (World Health Organization [WHO] Group 1), New York Heart Association functional class (NYHA FC) I, treated with bosentan and sildenafil as well as with anticoagulation. She was diagnosed with IPAH 10 years prior and her most recent right heart catheterization (RHC) showed a right atrial pressure of 7 mm Hg, mean pulmonary artery pressure (mPAP) of 48 mm Hg, cardiac output of 5.3 L/min, and pulmonary vascular resistance (PVR) of 7.1 Wood units. She was transferred to our intensive care unit with vaginal bleeding significant enough to cause systemic hypotension associated with a cardiac troponin leak and requiring multiple units of transfusions. Uterine artery embolization was attempted by interventional radiology at our institution, but the patient continued to have significant bleeding postprocedure. The patient ultimately was urgently taken to the operating room and underwent dilation and curettage while receiving general anesthesia. The patient tolerated the procedure well, was extubated, and transferred to the intensive care unit on 100% oxygen delivered by face mask.

The surgical team requests consultation regarding postoperative management. What advice would you give?
Clinical Trials Update: Recent Reports
Authors: Torres Fernando
Published: February 2019

The Clinical Trials Update highlights new and ongoing research trials that are evaluating therapies for PAH. In this issue, Dr Torres examines a study on the RELAX trial and a study on a revision to the Lung Allocation Score.
Clinical Trials Update
Authors: Levine Deborah J. , Torres Fernando
Published: February 2019

The Clinical Trials Update highlights new and ongoing research trials that are evaluating therapies for PAH. In this issue, Deborah Levine, MD, examines the PATENT-1 study results, findings from CHEST-1, and outcomes of the SERAPHIN trial.
Clinical Trials Update
Authors: Torres Fernando
Published: February 2019

The Clinical Trials Update highlights new and ongoing research trials that are evaluating therapies for PAH. In this issue, Fernando Torres, MD, examines a study on patients with pulmonary hypertension associated with left ventricular systolic dysfunction.
Hypoxic Pulmonary Vasoconstriction and Chronic Lung Disease
Authors: Swenson Erik R.
Published: February 2019

Hypoxic vasoconstriction in the lung is a unique and fundamental characteristic of the pulmonary circulation. It functions in health and disease states to better preserve ventilation-perfusion matching by diverting blood flow to better ventilated regions when local ventilation is compromised. As more areas of lung become hypoxic either with high altitude or global lung disease, then hypoxic pulmonary vasoconstriction (HPV) becomes less effective in ventilation-perfusion matching and can lead to pulmonary hypertension. HPV is intrinsic to the vascular smooth muscle and its mechanisms remain poorly understood. In addition, the pulmonary vascular endothelium, red cells, lung innervation, and numerous circulating vasoactive agents also affect the strength of HPV. This review will discuss the pathophysiology of HPV and address its role in pulmonary hypertension associated with World Health Organization Group 3 diseases. When sustained beyond many hours, HPV may initiate pulmonary vascular remodeling and lead to more fixed and less oxygen-responsive pulmonary hypertension if the hypoxic stimulus is maintained.
Diagnosis and Preoperative Evaluation of Chronic Thromboembolic Pulmonary Hypertension
Authors: van Kan Coen , Bresser Paul
Published: February 2019

Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as precapillary pulmonary hypertension (PH) as assessed by right heart catheterization, and results from incomplete resolution of the vascular obstruction associated with acute pulmonary embolism (PE). Pulmonary thromboendarterectomy (PTE) is the therapy of choice for CTEPH patients with surgically accessible thrombi.

Although associated with potential risks, PTE has been found to improve, and in many cases normalize pulmonary hemodynamics, functional status, and long-term survival. It is critical to undergo careful diagnosis and preoperative selection of patients who will most likely benefit from surgery. We have used published literature along with our personal experiences to review diagnosis of CTEPH and evaluation in advance of the PTE procedure.

In patients with PH or suspected PH, a complete diagnostic workup should be performed to identify the underlying etiology of the disease. Pulmonary angiography and right heart catheterization are the preferred assessment tools to diagnose CTEPH. PTE remains the treatment of choice, and for further evaluation of operability and preoperative risk patients should be referred to a CTEPH expert center.
Medical Therapy for Chronic Thromboembolic Pulmonary Hypertension
Authors: Rodriguez-Lopez Josanna , Channick Richard N.
Published: February 2019

Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary hypertension (PH) secondary to chronic emboli, obstructing the pulmonary arteries. This results in increased pulmonary vascular resistance and right ventricular failure. CTEPH is the only form of PH that is potentially curable, through a surgical procedure that removes the chronic emboli: pulmonary thromboendarterectomy (PTE). The first step in managing patients diagnosed with CTEPH is to determine if they are operable. The use of medical therapy should never delay referral for surgery, which should be done at a specialized center with expertise in CTEPH. Since a significant proportion of CTEPH patients are not surgical candidates, or are among the 10% to 15% of patients that have persistent or recurrent PH after surgery, there is a need for effective medical therapy.

The use of several pulmonary arterial hypertension (PAH)-targeted agents have been studied, mostly in small uncontrolled trials. A recent Phase 3 clinical trial found riociguat, a stimulator of soluble guanylate cyclase (sGC), to be effective for inoperable CTEPH.
A Treatment Algorithm for Pulmonary Arterial Hypertension
Authors: Galiè Nazzareno
Published: February 2019

The treatment algorithm for pulmonary arterial hypertension (PAH) represents graphically a sequence of operations that are needed for the management of patients. The treatment algorithm includes different types of recommendations with varying degrees of scientific evidence. The recommendations are based on information derived from different areas including clinical, hemodynamic, medical, interventional, pharmacological, and regulatory domains.

The current treatment algorithm is divided into 3 main sections: I) general measures, supportive therapy, referral strategy, acute vasoreactivity testing, and chronic treatment with calcium channel blockers; II) initial therapy with approved PAH drugs; III) clinical response to the initial therapy, combination therapy, balloon atrial septostomy, and lung transplantation. The European Society of Cardiology grades of recommendation and levels of evidence are adopted to rank the proposed treatments.
Future Therapies in PAH: Update on the New Landscape and Drugs in the Pipeline
Authors: Preston Ioana R.
Published: February 2019

Research in pulmonary hypertension (PH) in general and in pulmonary arterial hypertension (PAH) in particular has been extremely active in the past few years. The current therapeutic landscape includes multiple compounds shown to be active in modulating and ameliorating the pathological changes in the endothelin, nitric oxide (NO), and prostacyclin pathways. In addition, development of new compounds targeting pathways of pulmonary vascular remodeling due to inflammation, fibrosis, and oxidative stress is underway. This review summarizes the most recent achievements and newly conducted clinical trials—some with novel trial design—for treatment of PH and PAH.
PH Grand Rounds: Pulmonary Artery Filling Defects: Are They All the Same?
Authors: Levine Deborah J. , Al-Naamani Nadine , Channick Richard N. , Preston Ioana R.
Published: February 2019

Section editor's note: The diagnostic evaluation of pulmonary hypertension (PH) is an extensive, yet specific, process. Each individual study is significant, but it is truly the insightful analysis of the combination of studies that assists us most in making the correct diagnosis. In this issue's PH Grand Rounds, we congratulate Dr Al-Naamani and her colleagues for reminding us to consider a more in-depth examination of the data prior to making what seems to be an obvious diagnosis. This case not only imparts valuable information on this particular diagnosis, it also demonstrates how this type of thought process is vital to both the diagnosis and therapy for our patients.
Challenges in Endpoint Development for Pulmonary Hypertension Trials in Children
Authors: Ivy Dunbar
Published: February 2019

There are currently 12 medications approved for use in the treatment of pulmonary arterial hypertension (PAH) in adults. These include endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclins. However, in children there are no approved targeted PAH medications, with the exception of inhaled nitric oxide for treatment of hypoxemic respiratory failure in neonates. This review will address some of the challenges in the development of treatments for children, including lessons from recent trials, endpoints for clinical trials, and challenges with drug approval in children.
Research Reviews
Authors: Shlobin Oksana A. , Rich Jonathan D.
Published: February 2019

In this issue of Advances, section editors Oksana Shlobin, MD, and Jonathan Rich, MD, review findings from 2 recently published studies focused on outcomes and implications of the REVEAL registry.

Farber HW, Miller DP, Poms AD, et al. Five-year Outcomes of Patients Enrolled in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL). Chest. 2015 Jun 11. [Epub ahead of print]

Benza RL, Miller DP, Foreman AJ, et al. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease (REVEAL) analysis. J Heart Lung Transplant. 2015;34(3):356–361.
Sarcoidosis-Associated Pulmonary Hypertension: Diagnosis and Treatment
Authors: Baughman Robert P. , Engel Peter J.
Published: February 2019

Sarcoidosis-associated pulmonary hypertension (SAPH) has been reported in 10% of all sarcoidosis patients. In the United States, the prevalence is similar to that reported for scleroderma. There are several possible mechanisms for SAPH, including vascular compression, granulomatous angiitis, left ventricular (LV) dysfunction, and fibrosis of lung tissue. The prognosis of those with LV dysfunction is significantly better than those with precapillary pulmonary hypertension. Screening for SAPH includes evaluation of dyspnea by 6-minute walk test, echocardiography, and measurement of pulmonary artery diameter on computer tomographic scan. Right heart catheterization remains the definitive test for characterizing SAPH. Treatment for precapillary hypertension has been shown to improve pulmonary hemodynamics. However, it is still unclear whether such treatments will change the natural course of the disease, especially in those with severe fibrosis.
Pulmonary Hypertension in Chronic Myeloproliferative Disorders
Authors: Bhatia Sapna , Melendres Frederick , Melendres-Groves Lana
Published: February 2019

Chronic myeloproliferative disorders (CMPDs) are a heterogenous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood. Bone marrow histology shows hypercellularity and fibrosis in most of these disorders. The incidence of CMPD is estimated between 6 and 9 new cases per 100,000 yearly. CMPDs are incurable and are associated with a variable clinical course. Pulmonary hypertension (PH) is a well-recognized complication of CMPD, and when present, portends a poorer prognosis with median survival as low as several months, though this varies by the type of PH as well as the severity of the underlying CMPD. This review will serve to summarize the current knowledge of epidemiology, pathophysiology, diagnostic methods, clinical implications, and management of PH in CMPD.
PH Grand Rounds: Confronting the Challenge of Sarcoidosis-Associated Pulmonary Hypertension
Authors: Levine Deborah J. , Parikh Kishan S. , Fortin Terry , Rajagopal Sudarshan
Published: February 2019

Pulmonary hypertension (PH) associated with sarcoidosis (World Health Organization Group 5) carries a poor prognosis and likely occurs through multiple mechanisms. Routine monitoring and a high clinical suspicion must be maintained to establish early diagnosis. Imaging and other ancillary tests may suggest PH in these patients, but as with all PH groups, right heart catheterization is needed for confirmation and for differentiating contributors to PH. Although there appears to be a role for treatment in select patients with significant concomitant pulmonary arterial hypertension (PAH), pulmonary vasodilator therapy can also risk worsening hypoxia secondary to ventilation/perfusion mismatch. The medical management of patients with sarcoidosis-associated pulmonary hypertension (SAPH) will be better informed with further study in large, randomized trials. At this time, there are no US Food and Drug Administration-approved therapies, including PAH medications, for patients with SAPH.
Brain-on-a-chip Devices for Drug Screening and Disease Modeling Applications
Authors: Miccoli Beatrice , Braeken Dries , Li Yi-Chen Ethan
Published: February 2019

:

Neurodegenerative disorders are related to the progressive functional loss of the brain, often connected to emotional and physical disability and, ultimately, to death. These disorders, strongly connected to the aging process, are becoming increasingly more relevant due to the increase of life expectancy. Current pharmaceutical treatments poorly tackle these diseases, mainly acting only on their symptomology. One of the main reasons of this is the current drug development process, which is not only expensive and time-consuming but, also, still strongly relies on animal models at the preclinical stage.

:

Organ-on-a-chip platforms have the potential to strongly impact and improve the drug screening process by recreating in vitro the functionality of human organs. Patient-derived neurons from different regions of the brain can be directly grown and differentiated on a brain-on-a-chip device where the disease development, progression and pharmacological treatments can be studied and monitored in real time. The model reliability is strongly improved by using human-derived cells, more relevant than animal models for pharmacological screening and disease monitoring. The selected cells will be then capable of proliferating and organizing themselves in the in vivo environment thanks to the device architecture, materials selection and bio-chemical functionalization.

:

In this review, we start by presenting the fundamental strategies adopted for brain-on-a-chip devices fabrication including e.g., photolithography, micromachining and 3D printing technology. Then, we discuss the state-of-theart of brain-on-a-chip platforms including their role in the study of the functional architecture of the brain e.g., blood-brain barrier, or of the most diffuse neurodegenerative diseases like Alzheimer’s and Parkinson’s. At last, the current limitations and future perspectives of this approach for the development of new drugs and neurodegenerative diseases modeling will be discussed.
Expression of NRP-1 and NRP-2 in Endometrial Cancer
Authors: Oplawski Marcin , Dziobek Konrad , Grabarek Beniamin , Zmarzły Nikola , Dąbruś Dariusz , Januszyk Piotr , Brus Ryszard , Tomala Barbara , Boroń Dariusz
Published: February 2019

Background:

Neuropilins (NRPs) participate in many processes related to cancer development such as angiogenesis, lymphangiogenesis and metastasis. Although endometrial cancer is one of the most common gynecological cancers, it has not been studied in terms of NRPs expression.

Objective:

The aim of this study was to investigate the potential utility of NRPs as important factors in the diagnosis and treatment of endometrial cancer.

Methods:

Our study consisted of 45 women diagnosed with endometrial cancer at the following degrees of histological differentiation: G1, 17; G2, 15; G3, 13 cases. The control group included 15 women without neoplastic changes. The immunohistochemical reactions were evaluated using light microscopy.

Results:

We did not detect the expression of NRP-1 and NRP-2 in the control group. NRP-1 expression was found exclusively in cancer cells. It was higher in G2 and G3 and reached about 190% of G1. NRP-2 expression was observed in the endothelium and was similar across all three cancer grades. In cancer cells, NRP-2 expression increased with the degree of histological differentiation.

Conclusion:

NRP1 and NRP2 are candidates for complementary diagnostic molecular markers and promising new targets for molecular, personalized anticancer therapies.
Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma
Authors: Sánchez-Crisóstomo Isabel , Fernández-Martínez Eduardo , Cariño-Cortés Raquel , Betanzos-Cabrera Gabriel , Bobadilla-Lugo Rosa A.
Published: February 2019

Background:

Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs.

Review and Conclusion:

Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.
Targeting DNA Double-Strand Break (DSB) Repair to Counteract Tumor Radio-resistance
Authors: Zhao Yucui , Chen Siyu
Published: February 2019

During the last decade, advances of radiotherapy (RT) have been made in the clinical practice
of cancer treatment. RT exerts its anticancer effect mainly via leading to the DNA Double-Strand
Break (DSB), which is one of the most toxic DNA damages. Non-Homologous End Joining (NHEJ)
and Homologous Recombination (HR) are two major DSB repair pathways in human cells. It is
known that dysregulations of DSB repair elicit a predisposition to cancer and probably result in resistance
to cancer therapies including RT. Therefore, targeting the DSB repair presents an attractive
strategy to counteract radio-resistance. In this review, we describe the latest knowledge of the two
DSB repair pathways, focusing on several key proteins contributing to the repair, such as DNA-PKcs,
RAD51, MRN and PARP1. Most importantly, we discuss the possibility of overcoming radiation resistance
by targeting these proteins for therapeutic inhibition. Recent tests of DSB repair inhibitors in
the laboratory and their translations into clinical studies are also addressed.
Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells
Authors: Chan Elaine Wan Ling , Yeo Emilia Tze Ying , Wong Kelly Wang Ling , See Mun Ling , Wong Ka Yan , Gan Sook Yee
Published: February 2019

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that
eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive,
increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are
associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological
properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little
is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory-
mediated ailments.

Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts
obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the
production of pro-inflammatory mediators.

Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate
(REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and
mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and
RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay.
BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective
effect was assessed using MTT assay.

Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression
of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and
RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was
correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS
root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in
microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity
either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y
cells against these inflammatory mediators.

Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ-
induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a
potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease
(AD).
Therapeutic Potential of Melatonin in the Regulation of MiR-148a-3p and Angiogenic Factors in Breast Cancer
Authors: Lacerda Jéssica Zani , Ferreira Lívia Carvalho , Lopes Beatriz Camargo , Aristizábal-Pachón Andrés Felipe , Bajgelman Marcio Chaim , Borin Thaiz Ferraz , de Campos Zuccari Debora Aparecida Pires
Published: February 2019

Background:

The high mortality rate of breast cancer is related to the occurrence of metastasis, a process that is promoted by tumor angiogenesis. MicroRNAs are small molecules of noncoding mRNA that play a key role in gene regulation and are directly involved in the progression and angiogenesis of various tumor types, including breast cancer. Several miRNAs have been described as promoters or suppressors angiogenesis and may be associated with tumor growth and metastasis. Melatonin is an oncostatic agent with a capacity of modifying the expression of innumerable genes and miRNAs related to cancer.

Objective:

The aim of this study was to evaluate the role of melatonin and the tumor suppressor miR- 148a-3p on angiogenesis of breast cancer.

Method:

MDA-MB-231 cells were treated with melatonin and modified with the overexpression of miR-148a-3p. The relative quantification in real-time of miR-148a-3p, IGF-IR and VEGF was performed by real-time PCR. The protein expression of these targets was performed by immunocytochemistry and immunohistochemistry. Survival, migration and invasion rates of tumor cells were evaluated. Finally, the xenograft model of breast cancer was performed to confirm the role of melatonin in the tumor.

Results:

The melatonin was able to increase the gene level of miR-148a-3p and decreased the gene and protein expression of IGF-1R and VEGF, both in vitro and in vivo. In addition, it also had an inhibitory effect on the survival, migration and invasion of breast tumor cells.

Conclusion:

Our results confirm the role of melatonin in the regulation of miR-148a-3p and decrease of angiogenic factors.
Influence of Women Age on Berries Consumption: The Role of Liking and Properties of Berries as Determinants of Their Intake
Authors: Lares-Michel Mariana , Housni Fatima Ezzahra , Cervantes Virginia Gabriela Aguilera , Carmona María Del Carmen Barragán , Cañedo Claudia Llanes
Published: February 2019

Due to the benefits of berries to health and aging in women and the fact that as women age, they are increasingly concerned about remaining healthy and looking young, the aim of this paper is to determine if the consumption of berries among women is influenced by their age; also, to identify if the reasons why berries are ingested vary with age. This study evaluated berries intake and motives of consumption of 240 adult women from Jalisco, Mexico, ranging from 18 to 65 years old, divided into three groups: Young Adult Women (YAW, from 18 to 35 years old), Middle-Aged Adult Women (MAW, from 36 to 55 years old) and Older Adult Women (OAW, from 56 to 65 years old). Berries (blueberry, raspberry, strawberry and blackberry) consumption was collected by an adapted Food Consumption Frequency Questionnaire validated for Mexican population, and intake reasons were assessed by a qualitative section. Spearman’s Correlations, ANOVA and Bonferroni test were done. While berries consumption lowers in the MAW group, it increases when women reach the advanced adulthood. YAW consumes berries mainly because of liking and OAW due to its properties. Only 60% of OAW consumes berries and frequency of consumption is occasional in all women, so policies to increase berries intake are needed.
A Comparison of Women’s Travel to Mammography Services and Average Week Day Trip Length
Authors: Gaans Dr. Deborah Van , Carroll Dr. Suzanne , Coffee Dr. Neil , Miles Ms. Catherine , Warner-Smith Mr. Matthew , Daniel Prof. Mark , Roder Prof. David
Published: February 2019

Long travel distances/times to a mammography service may act as a barrier that hinders women from seeking screening mammography on a recommended schedule. Average weekday trip length data from the New South Wales Travel Survey was compared with the average distance women travelled to a mammography service, the difference was tested using the Wilcoxon Signed Rank Test. The distance travelled to mammography services was statistically greater than the average week day trip length from the New South Wales Travel Survey (4.3 km, 95% CI 3.3 to 5.9 kms, p,0.001). This study has identified that within New South Wales there is a significant difference between average week day trip length travel and client travel to mammography services. Therefore, highlighting that women are undertaking a greater than normal travel burden to access mammography services. The comparison of normal weekday travel and travel to mammography services has enabled the burden of travel to mammography services to be identified. Reducing the burden of travel to mammography services is pivotal to increasing the utilization of mammography services and reducing the inequalities in health comes.
Human Immunodeficiency Virus Nephropathy in Central Africa: The Value of Renal Ultrasound
Authors: Kinfuidi Nancy Moyo , Bompeka François Lepira , Mangani Nazaire Nseka , Kalambayi Patrick Kayembe , Dikamba Nelly , Kisile Olive , Aloni Michel , Mfutu Pepe Ekulu , Tshibola Jean Mukaya , Tshikwela Michel Lelo
Published: February 2019

Introduction: HIV-Associated Nephropathy may shorten the life expectancy of affected patients. Its early detection is beneficial for the indication of treatment and hence prevention of progression to the end-stage of renal failure. The final diagnosis requires renal biopsy which may be difficult in some African area; clinical and ultrasound criteria may be helpful. The aim of this study was twofold: to characterize renal sonographic changes in HIV-positive patients with HIV associated Nephropathy and to investigate the correlation between renal sonographic changes and histological lesions in central Africa.

Methods: A prospective and multi-center study conducted from January 2013 to July 2015 included, for renal ultrasound evaluation of the length, thickness and echogenicity, forty two of the 334 biologically confirmed HIV-positive patients who presented with significant proteinuria suggestive of HIV associated Nephropathy. And transcutaneous renal biopsy with histopathology has been performed in 16 patients of them. Statistical analyzes were used.

Results: There were 100 men and 234 women; proteinuria was positive in 42 patients, (12.6%). The average length of the kidneys was 111 ± 8 mm (normal), with 10% of patients with pathological values (5% with kidneys of reduced size and 5%, increased size). The kidneys had an average thickness of 44 ± 5 mm (normal), with 21% of patients presenting an increase in renal thickness. Quantitative echogenicity was calculated at 1.492 ± 0.793 (normal), with 79% of patients with increased quantitative echogenicity. Of the 16 patients biopsied, all had tubulo-interstitial lesions, and 75% of them associated with glomerular lesions. In simple correlation analysis, tubular dilatation was positively and significantly related to quantitative echogenicity (r = 0.67, p < 0.01) and to renal parenchyma thickness (r = 0.67; 0.85, p ? 0.05). The relationship between the other parameters studied did not reach statistical significance. In multiple linear regression, glomerular hyalinosis, glomerular proliferation, tubular dilatation, tubular atrophy, interstitial fibrosis, and interstitial inflammation emerged as the main determinants of quantitative echogenicity; however, the relationship was statistically significant only for tubular dilatation (? = 0.305, p = 0.034).
Conclusion: The present study showed the characteristic of renal change and the relation with histology found in central Africans patients.
DANO AMBIENTAL TRABALHISTA E A FORÇA PROBATÓRIA DOS ESTUDOS EPIDEMIOLÓGICOS SOBRE CÂNCER OCUPACIONAL
Authors: PESSOA ANDRE MAGALHÃES , De Aguiar Julio Cesar
Published: February 2019

O propósito deste artigo é analisar a força probatória dos estudos epidemiológicos que relacionam câncer a exposições ocupacionais específicas, em especial para a demonstração do nexo de causalidade entre a atividade laboral e o adoecimento. Para alcançar essa finalidade, utilizou-se como fonte de pesquisa a teoria geral da prova e estudos epidemiológicos sobre o câncer ocupacional. Foi necessário examinar o sistema de provas diretas e por indícios, à luz do explanacionismo, valendo-se do método da inferência para melhor explicação. Ao final, foi feito uma breve diagnose diferencial no potencial probatório dos estudos epidemiológicos nas ações para tutela de direitos individuais e nas ações para a tutela de direitos coletivos.