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This study explores the potential of 1H-NMR spectroscopy-based metabolic profiling in various biofluids as a diagnostic and predictive modality to assess disease severity in individuals with 5q spinal muscular atrophy. A total of 213 biosamples (urine, plasma, and CSF) from 153 treatment-naïve patients with SMA across five German centers were analyzed using 1H-NMR spectroscopy. Prediction models were developed using machine learning algorithms which enabled the patients with SMA to be grouped according to disease severity. A quantitative enrichment analysis was employed to identify metabolic pathways associated with disease progression. The results demonstrate high sensitivity (84–91%) and specificity (91–94%) in distinguishing treatment-naïve patients with SMA from controls across all biofluids. The urinary and plasma profiles differentiated between early-onset (type I) and later-onset (type II/III) SMA with over 80% accuracy. Key metabolic differences involved alterations in energy and amino acid metabolism. This study suggests that 1H-NMR spectroscopy based metabolic profiling may be a promising, non-invasive tool to identify patients with SMA and for severity stratification, potentially complementing current diagnostic and prognostic strategies in SMA management. [ABSTRACT FROM AUTHOR]

Abstract Background 5q spinal muscular atrophy (SMA) is a disabling and life-limiting neuromuscular disease. In recent years, novel therapies have shown to improve clinical outcomes. Yet, the absence of reliable biomarkers renders clinical assessment and prognosis of possibly already affected newborns with a positive newborn screening result for SMA imprecise and difficult. Therapeutic decisions and stratification of individualized therapies remain challenging, especially in symptomatic children. The aim of this proof-of-concept and feasibility study was to explore the value of 1H-nuclear magnetic resonance (NMR)-based metabolic profiling in identifying non-invasive diagnostic and prognostic urinary fingerprints in children and adolescents with SMA. Results Urine samples were collected from 29 treatment-naïve SMA patients (5 pre-symptomatic, 9 SMA 1, 8 SMA 2, 7 SMA 3), 18 patients with Duchenne muscular dystrophy (DMD) and 444 healthy controls. Using machine-learning algorithms, we propose a set of prediction models built on urinary fingerprints that showed potential diagnostic value in discriminating SMA patients from controls and DMD, as well as predictive properties in separating between SMA types, allowing predictions about phenotypic severity. Interestingly, preliminary results of the prediction models suggest additional value in determining biochemical onset of disease in pre-symptomatic infants with SMA identified by genetic newborn screening and furthermore as potential therapeutic monitoring tool. Conclusions This study provides preliminary evidence for the use of 1H-NMR-based urinary metabolic profiling as diagnostic and prognostic biomarker in spinal muscular atrophy.

Phenylketonuria (PKU) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase gene. Depending on the severity of the genetic mutation, medical treatment, and patient dietary management, elevated phenylalanine (Phe) may occur in blood and brain tissues. Research has recently shown that high Phe not only impacts the central nervous system, but also other organ systems (e.g., heart and microbiome). This study used ex vivo proton nuclear magnetic resonance (1H-NMR) analysis of urine samples from PKU patients (mean 14.9 ± 9.2 years, n = 51) to identify the impact of elevated blood Phe and PKU treatment on metabolic profiles. Our results found that 24 out of 98 urinary metabolites showed a significant difference (p < 0.05) for PKU patients compared to age-matched healthy controls (n = 51) based on an analysis of urinary metabolome. These altered urinary metabolites were related to Phe metabolism, dysbiosis, creatine synthesis or intake, the tricarboxylic acid (TCA) cycle, end products of nicotinamide-adenine dinucleotide degradation, and metabolites associated with a low Phe diet. There was an excellent correlation between the metabolome and genotype of PKU patients and healthy controls of 96.7% in a confusion matrix model. Metabolomic investigations may contribute to a better understanding of PKU pathophysiology.

Abstract Cognitive radio is a technology developed for the effective use of radio spectrum sources. The spectrum sensing function plays a key role in the performance of cognitive radio networks. In this study, a new threshold determination method based on online learning algorithm is proposed to increase the spectrum sensing performance of spectrum sensing methods and to minimize the total error probability. The online learning algorithm looks for the optimum decision threshold, which is the most important parameter to decide the presence or absence of the primary user, using historical detection data. Energy detection- and matched filter-based spectrum sensing methods are discussed in detail. The performance of the proposed algorithm was tested over non-fading and different fading channels for low signal-to-noise ratio regime with noise uncertainty. In the conclusion of the simulation studies, improvement in spectrum sensing performance according to optimal threshold selection was observed.

Objective: The purpose of this article is to assess whether the relationship that existed between Ronald Reagan and the Republican Party could reasonably be characterized as one of personalization/de‐institutionalization of the party.1 Methods: The authors employ the common conceptual framework developed for this special issue. Evidence is drawn from both popular journalism and scholarly sources. Results and Conclusion: While bits of evidence exist for personalization, especially with regard to the external dimension, the collective evidence stops short of what is required to be considered de‐institutionalization of the party. [ABSTRACT FROM AUTHOR]

Without any financial protection out of pocket health expenses are essential both because their increase causes difficulties in accessing higher quality health services for households and more importantly because it complicates access to most basic health services. As a result of the Health Transformation Program in practice in the Turkish healthcare system since 2003, significant changes have been done in all layers of the health system. Turkish Statistics Institute (TurkStat) publishes the ratio of households that bear catastrophic health expenditures since 2002. According to TurkStat data, the ratio of households with catastrophic expenditure has fallen from 0.81% in 2002 to 0.17% in 2011 with the health transformation project. However, it has started to rise since 2012 and has reached 0.31% in 2014. This study aims to evaluate the expenditure items that may have caused the rise of the ratio of households with catastrophic health expenditures since 2012, which had previously dropped with the Health Transformation Program that has caused fundamental changes in health policies. Methodology and definitions presented in the article named “Distribution of health payments and catastrophic expenditures: Methodology” by Ke Xu published by the World Health Organization in 2005 have been used. Percentages of health expenditure items among the total expenditure of households with positive health expenditure and households with catastrophic health expenditure between 2007 and 2014 have been evaluated using descriptive analysis. Findings have been interpreted in light of the health policies in practice between 2007 and 2014. An overview of the impact of the health policies reveals that medicine expenditures have decreased both for household and public health expenditures. Despite the impact of policies on the pharmaceutical industry was criticized by the industry, the positive impact can be seen by the decrease in the spending on medicine for households spending on health. Hospital service with positive health expenditure is seen to decrease health expenditure. The reasons for the increase in households with catastrophic health expenditure need further research. As a result, the study strives to discuss the possible policy reasons for the observed effects.

BACKGROUND: Reimbursement agencies are increasingly adopting innovative reimbursement approaches for new and expensive technologies. Social Security Institution (SSI), Turkey`s reimbursement agency, established the Alternative Reimbursement Commission (ARC) on February 10, 2016. This study aimed to understand the implementations of market access agreements in recent years in Turkey. METHODS: Decisions of the Health Services Pricing Commission published in the official gazette , and information from the Turkey Pharmaceuticals and Medical Devices Agency, the Abroad Drug List, Health Implementation Communique published by SSI with additional lists, such as the Annex-4A List of Reimbursed Medicines and the Annex-4C Abroad Drug Price List, were used. The data was transferred to Windows Office Excel files, and a descriptive analysis was conducted and evaluated by two market access experts. RESULTS: There were 57 drugs included in the coverage of reimbursement with alternative reimbursement since the application was started in Turkey. 35 of them were added to Annex-4A and 22 of them to Annex-4C. Furthermore, 45.6% of the drugs had an Anatomic Therapeutic Chemical Classification (ATC) code of l-antineoplastic and immunomodulating agents, 28% were orphan drugs, 44 of them had a confidential discount rate, and financial-based agreement models were preferred for nearly all agreements. CONCLUSIONS: Turkey has been implementing market access agreements since mid-2016. In the past 3 years, 57 drugs have been covered for reimbursement under the new implementation. Further analysis should be conducted to understand the decision-making process involved.

Bu çalışmanın amacı, Türkiye’de meme kanseri tedavisinde ruhsatsız ve endikasyon dışı ilaç kullanımını değerlendirmektir. Bu çalışmaya trastuzumab veya diğer endikasyon dışı ilaç kullanımı için başvuruda bulunan olan ErbB-2 pozitif tümörleri olan metastatik meme kanseri olan hastalar (n = 1317) alındı. En çok üniversite hastanelerinden başvurular vardı, diğer başvurular ise eğitim ve araştırma hastaneleri ve özel hastanelerden geliyordu. Bu durum, üniversite hastanelerinin endikasyon-dışı ilaç kullanımına ihtiyaç duyabilecek hastaları daha fazla kabul etmesinden kaynaklanabilir.

OBJECTIVE: Preterm premature rupture of membranes (PPROM) has unfavorable consequences for the neonate and the mother if it occurs before 24 weeks of gestation. We aim to present our series to elucidate the course of previable PPROM and to detect maternal and neonatal outcomes. STUDY DESIGN: A single-centered retrospective cohort study that involves singleton patients diagnosed with spontaneous PPROM before 24 weeks. Data were retrieved from medical records, and maternal and neonatal outcomes were noted. RESULTS: Seventy-eight women were diagnosed with PPROM before 24 weeks, 42 patients (54%) opted for termination of pregnancy, and seven patients (9%) had spontaneous abortion. Twentynine patients (37%) gave live birth after a median latency of 47 days. Neonatal complications were respiratory distress syndrome (n=19; 65%), early sepsis (n=10; 34%), late sepsis (n=5; 17%), bronchopulmonary dysplasia (n=5;17%), retinopathy of prematurity (n=3; 10%), pneumothorax (n=5; 17%), intracranial hemorrhage (n=2; 6%), necrotizing enterocolitis (n=1; 3%) and meningitis (n=1; 3%). In the liveborn group, the neonatal survival rate was 62%. Of the survivors, twelve babies (66%) were discharged without composite neonatal morbidity. Maternal complications in the expectant management group included clinical chorioamnionitis (n=12, 33%) and placental abruption (n=2, 5%). CONCLUSION: In previable PPROM, overall half of the babies survive after expectant management. While a prolonged latency period and subsequent delivery at advanced gestational ages improve neonatal outcomes, such a conservative approach poses a substantial risk for chorioamnionitis. [ABSTRACT FROM AUTHOR]

Aim: Kangal dogs, known as guard dogs in many countries of the world, have been found to eat their own puppies during their first 24 h following birth, which is called as maternal cannibalism. Adenosine deaminase (ADA) and xanthine oxidase (XO) are important enzymes for purine metabolism. In this study, the aim is to evaluate ADA and XO activities in Kangal dogs with maternal cannibalism. Materials and Methods: The material of the study consists of the blood sera of Kangal dog breed with and without maternal cannibalism in the breeders around Sivas city and its districts. ADA and XO activities in blood serum of these animals were investigated by spectrophotometric method. Results: ADA activities in Kangal dogs with maternal cannibalism were increased to the control group without maternal cannibalism (p