The clinical applications of sensing tools  for the monitoring of physiologically important analytes are very common. Nowadays, the biosensors are being increasingly used to detect physiologically important analytes in real biological samples . This review focuses on biosensors that can be applied to continuous, time-resolved measurements with fluorescence. The material presents the fluorescent biosensors for the detection of neurotransmitters, hormones, and other human metabolites as glucose, lactate or uric acid. The construction of microfluidic devices based on fluorescence uses a variety of materials, fluorescent dyes, types of detectors, excitation sources, optical filters, and geometrical systems. Due to their small size, these devices can perform a full analysis. Microfluidics-based technologies have shown promising applications in several of the main laboratory techniques, including blood chemistries, immunoassays, nucleic-acid amplification tests. Of the all technologies that are used to manufacture microfluidic systems, the LTCC technique seems to be an interesting alternative. It allows easy integration of electronic and microfluidic components on a single ceramic substrate. Moreover, the LTCC material is biologically and chemically inert, and is resistant to high temperature and pressure. The combination of all these features makes the LTCC technology particularly useful for implementation of fluorescence-based detection in the ceramic microfluidic systems. Biosensors are analytical tools that measure the presence of a single molecular species in complex mixtures by combining the exquisite molecular recognition properties of biological macromolecules with signal transduction mechanisms that couple ligand binding to readily detectable physical changes . These aThe choice of the substrates for the analytical applications depends on the transduction methods; i.e., fluorescence, chemiluminescence, or amperometry—and on the purpose of the analytical measurements . VariousAdvances in miniaturization, nanotechnology, and microfluidics, together with developments in cloud-connected point-of-care (POC) diagnostics technologies are pushing the frontiers of POC devices toward cost-reasonable, easy to use, and enhanced sensitivity molecular-level diagnostics. The merger of various bio-sensing systems within smartphone-integrated electronic readers provides proper on-site and real-time diagnostics based on various types of chemical and biological targets . This review focuses on biosensors that can be applied to continuous, time-resolved measurements with fluorescence. The material presents the fluorescent biosensors for the detection of neurotransmitters, hormones, and other human metabolites as glucose, lactate, or uric acid.One of the most dynamically developing areas of modern medicine is, according to the motto “prevention is better than cure”, clinical diagnostics. Researchers are focused not only on improving existing and constructing new analytical devices, but also more and more accurate methods of detecting chemical or biochemical compounds that show how the occurrence of given pathologies are being developed. During quick tests, so-called “bedside”, the time of the analysis is extremely important. Tests carried out in intensive care centers require the maximum time to wait for the results of the patient, which is often caused by the need to take immediate therapeutic decisions (sometimes access to the parameters obtained is necessary at the time). The term turnaround time (TAT) defines the time in which the sign should be made .For the sake of many stages during the analysis , the TAT behavior and the receipt of results in real time are not ensured. Hence, research is more often used as a point-of-care (POC), which means research in the place of patient care or bedside laboratory tests. The beginning of the use of diagnostic systems for POC research is considered to be the 60’s and 70’s of the 20th century, which is the date of development and implementation of a glucometer, an all-in-one apparatus enabling independent measurement of glucose in blood. Towards the end of the 1970s, one-time tests, such as pregnancy tests, have revolutionized the testing of disposable household products. Currently, we can find fertility tests, menopausal tests, tests detecting the presence of psychoactive substances, or the presence of infection. Designing devices allowing POC analysis in the clinical sense (enabling continuous monitoring of given substances) has been developing rapidly for two decades, enabling quick and sensitive “bedside” diagnostics . Th. Th35]. 3O4 nanoparticles. Fe3O4 nanoparticles have been modified with acrylic acid (AA) and fluorescein. 17β-estradiol was added to the thus-modified particles due to its complementary affinity for fluorescein. The change in fluorescence intensity indicated the 17β-estradiol concentration in the test solution [The fluorescence strategy is often used in sensing systems, for example Weina Ming et al. developed a fluorescent method for the detection of 17β-estradiol in aqueous solutions. They used the phenomenon of competitive hormone adsorption with fluorescein, which in the proposed system serves as a fluorophore particle. Functionalization was performed on a new magnetic core-shell material that combines the surface application technique and the ability to separate magnetic Fesolution .A fluorescent-based biosensor for the detection of 17β-estradiol was constructed by Yildirim et al. using specific short chain oligonucleotides (aptamers) . For thi−6 ng mL−1. The constructed biosensor was used for the detection and determination of 17β-estradiol in human urine.A gold nanoparticles-based fluorescence immunoassay was presented  to ultra−1.A TIRF-based biosensor for detection of steroid hormone testosterone was also constructed . For thi−6 ng mol−1 [Biosensors for detecting and determining insulin have also been constructed ,40. Yuhung mol−1 .Neurochemical methods are generally used for mechanism investigations of brain action, understanding the presence of neurotoxins during some disorders, and also for understanding the relationship between chemistry in central nervous system (CNS) and the emotional state ,43. The Determining the level of neurochemicals in body fluids is essential for the industry. For instance in environmental monitoring, food analysis or clinical diagnostics, is currently not available. This chapter presents new optical methods for neurotransmitter determination, which also in the future will be capable of monitoring these compounds in body fluids.The main mediators of the autonomic nervous system, which have a stimulating effect on the sympathetic nervous system, are: dopamine, epinephrine  and norepinephrine , which belongs to the catecholamines, and serotonin (5HT) (monoamine). Monitoring and detection of these molecules is extremely important in modern medicine, specifically for helping point-of-care measurements in hospitals ,60.Generally, the endogenous catecholamine concentration, which has been measured for patients without any diagnosed disorders, was approximately 150–800 ng/L for NE and 10–50 ng/L for EP and dopamine (DA) . Their lDA plays a significant role in movement, muscle tension control, pain processing, arousal, motivation, and reward . As a reFRET (Förster Resonance Energy Transfer),FLIM (Fluorescence Lifetime Imaging),FCS (Fluorescence Correlation Spectroscopy),FI (changes in Fluorescence Intensity).To determine the catecholamines using an optical detection bio-system, fluorescence-based biosensors are generally used . FluoresFRET is a method involving the radiation-less transfer of energy from a “donor” fluorophore to an “acceptor” fluorophore . Such a FLIM is a technique used for imaging processes which take place in living cells. Such an occurrence enables an average lifetime when a molecule remains in its excited state after absorbing a photon to be detected . Such a FCS is based on small deviations in an unprompted fluorescence intensity of the sample and the obtained signal provides information about the kinetics of thermodynamic processes related to reversible fluorescence changes ,67.FI is a method based on the direct measurement of fluorescence intensity (fluorescence emission) to the response of the system to excitation. FI is generally employed for fluorescence investigations of biosensors containing an enzyme in the bioreceptor part ,69.At present, there is no available diagnostic tool for the sensitive determination of catecholamines, which is extremely important in modern medicine. Optical bio-systems are a very promising candidate for analytical sensors, because they provide fast, simple, cheap, and sensitive analysis of the investigated sample. In the literature are presented fluorescent detection methods for catecholamines investigations, however, most of them are connected with DA detection ,71. In t−8 M concentrations [Baron et al. proposed a detection method for neurotransmitters using tyrosinase in a bioreceptor layer: dopamine, L-DOPA, epinephrine, and norepinephrine, which mediate the generation and growth of Au nanoparticles (Au-NPs). The assumption of measurements was based on the plasmon absorbance of the Au-NPs, which allows for the quantitative colorimetric detection of the neurotransmitters. Authors obtained good results of the detection limit  for a linear response in the range of 40–200 µM . Nikoleltrations . Chen ettrations .2+ ions, and then the addition of a DA molecule, which causes the retrieval fluorescence by binding with the metal ion and removing it from the surface of BSA–Au NCs. The detection limit for such an arrangement equals to 0.01 µM and the linear response of DA in the range of 0.5–4 µM [Lin et al. introduced the DNA-biosensor for DA detection, based on a DNA-mediated silver nanostructure, which consisted of a large fluorescence enhancement resulting from specific binding of intercalating dye with the DNA that is released by DA from the nanoparticles. Such a prepared detection system was linear in a wide range of concentrations, from 0–200 nM, and showed great a detection limit of 6 nM . Aswathy0.5–4 µM .There has been also presented the microfluidic ceramic settings for dopamine detection based on polydopamine-graphene quantum dots with LOD 80 nM [Searching for new approaches for neurotransmitter determination is a key factor in improving clinical diagnostics, which is directly connected with the point-of-care measurements. Such analytical tools will, in the future, ensure fast, simple, and bedside analysis of important biomolecules.Highly selective and sensitive detection of biologically important structures, including small molecules  and whole cells , is critical in clinical analysis, environmental screening, food safety, and bioprocess monitoring.Many studies in recent decades have focused on the development of sensor systems for the determination and monitoring of lactate concentration, which are a very important factor in clinical diagnostics, sports medicine, and food technology . During Uric acid  is the main end product of purine nucleotide metabolism, mainly found in urine and serum ,90. The Glucose is one of the most important molecules in the body. It performs the basic function in metabolic processes and is the main source of energy in cellular metabolism. As with other important molecules, glucose disturbances can cause many serious diseases such as diabetes or hypoglycemia. As the incidence of diabetes continues to increase, it is extremely important to monitor the level of glucose in the blood in order to accurately diagnose diabetes .The most commonly used biologically active compound used to detect lactate is lactate dehydrogenase (LDH) . Sensorsd-glucose and oxygen to d-glucono-1,5-lactone and hydrogen peroxide. In the case of a fluorescent-based biosensor for glucose determination, the most widely used is glucose oxidase (GOx), which catalyzes the conversion of One of the used strategies for fluorescence-based glucose sensing is the method based on the intrinsic fluorescence of the enzyme. Due to the presence of tyrosine and tryptophan in protein molecule, GOx exhibits a strong fluorescence signal with excitation at 224 and 278 nm, and emission at 334 nm . A fluorEnzymatic systems can also be used to construct specific uric acid sensors. The detection process consists in carrying out a series of enzymatic reactions using uricase and horseradish peroxidase (HRP). The reaction consists in the initial oxidation of uric acid to allantoin and hydrogen peroxide . The resVarious biosensors based on fluorescence measurements for the determination of lactate have been developed. Yong-Sheng et al. used the enzyme lactate dehydrogenase (LDH) for the construction of a biosensor. LDH was immobilized in the inner surface in a medical capillary. The constructed biosensor can be applied for rapid and sensitive determination of lactate in ferment foodstuff, leechdom, and blood samples with LOD 0.45 mM . Zheng eFluorescence strategies can be also used for the determination of uric acid. Azmi et al. designed an enzymatic biosensor to determine the concentration of uric acid in urine . For the−9 mol L−1.Biosensors for the detection of glucose have also been constructed. Lin et al. proposed an enzyme based platform for the detection of this carbohydrate. The sensing system was constructed by using the label-free MIL-53(Fe) nanozyme and glucose oxidase . OccurriChen et al. designed an enzymatic biosensor for glucose detection, based on the FRET phenomenon . The CdSAyranci et al. constructed another platform for measuring changes in fluorescence intensity, produced by the copolymerization of an electroactive rhodamine-based monomer (RDC) and a monomer containing a functional group (SNS) allowing binding of the enzyme . The plaSeveral technologies are used for microfluidic system manufacturing, primarily: silicon, glass, polymer, and ceramic. The first can incorporate very fine structures by using various etching techniques . These processes are very well known and widely used, as they derivate from electronic component manufacturing methods. Therefore, highly integrated Micro Electro-Mechanical Systems (MEMS) are very common and cheap in mass production. However, development and small scale manufacturing are quite expensive due to high material and processing costs. The main issue in fluorescence measurement is material transparency. Therefore, silicon technology cannot be used as a standalone. In the case of silicon microsystems, bonding with glass is used in the vast majority of cases, as it is carried out using typical silicon bonding techniques, such as anodic bonding . Full glPolymer microsystems form a vast group. Nonetheless, the main trends can be separated: molding, 3D printing, and layer structuration. While the first is well established, the second is only just emerging, and the third is rather niche as a microfluidic technique. Molded structures are made primarily of optically transparent polydimethylsiloxane (PDMS). Forms can be made from various materials: from silicon (soft lithography) to 3D printed polymers. This method is inexpensive and relatively easy to develop. In order to obtain closed canals, the mold needs to be bonded, either to another PDMS structure or a different material. A plasma treatment is a common method. Due to good optical properties this material is very suitable for a fluorescence system manufacturing standalone  or in taAnother technique, 3D printing of microfluidic structures is very promising. The most common and inexpensive method, Fused Deposition Modelling (FDM), also known as Fused Filament Fabrication (FFF), uses thermoplastic polymers, as in typical plastic processing, in the form of a cable that is heated and then pushed out through an extruder. This method, although very inexpensive in both equipment and materials, struggles with shape fidelity, reproducibility, leaking and transparency. The inkjet 3D printers are much more capable, although 10–100 times more expensive . ForemosThe layer structuration method is based on cutting or engraving patterns on subsequent polymer substrates using a cutting plotter, milling machine or laser system, and then laminating them at elevated temperature. Polymethylmethacrylate (PMMA) and polyvinylchloride (PVC) are most commonly used to produce microfluidic chips using this technique. Main issues of this method are poor canal quality, detail resolution and shape fidelity, as well as deterioration of transparency in case of laser engraving. Ceramic technologywas developed primarily in order to manufacture microelectronic devices. It is the least known, however, the immense capabilities of developing 3D structures in Low Temperature Cofired Ceramic (LTCC) proved to be very useful in microfluidics. The LTCC substrates are composed of ceramic particles and glass. It has the possibility of cofiring with thick film layers , which is useful not only for the integration of electronic components but also for the deposition or immobilization of functional materials. One of the first efforts to obtain a fluorescence measurement in a ceramic system was a sensor developed by Golonka et al. . It consCouceiro et al. ,122 haveThe LTCC technology is a very promising alternative for the fabrication of microsystems for analytical chemistry, biology, and medicine. It has a unique feature to integrate electronics and microfluidics in a single module. The manufacturing process of LTCC structures begins with tape casting. From a reservoir containing ceramic-glass powder, mixed with solvent and dispersant, the mixture is transferred onto a support foil and then dried. Thus, the obtained intermediate product is called Green Tape and is very easy to process, usually by milling or laser ablation. Multiple sheets can be laminated in order to develop any 3D structure, just as in additive manufacturing—layer by layer. Moreover, LTCC is foremost a microelectronic material, so integration of electric interconnections is effortless, by use of thick film technology. The last step is firing in ca. 850 °C. More details about the LTCC technology can be found in ,125.2 blank at the top,4 with 500 µm wide canals and voids for optical fiber and fluidic ports,2 glass plate and1 with a 6 × 6 mm2 window for fluorescence measurement.1 at the bottom, with a 2 × 2 mmIn this work, we want to present the LTCC microfluidic system for fluorescence measurements developed by our group. It consists of a microfluidic chip and base station. Schematic views of both parts are shown in ® DP951 PX LTCC tapes, 254 μm thick. Patterning was carried out using LPKF Protolaser U laser system (λmax = 355 nm). Afterwards, a sodium glass window was inserted in a special void and all layers were stacked together. The lamination process was carried out at a pressure of 10 MPa and a temperature 70 °C for 10 min in an isostatic press. Structures were fired in a box furnace Nabertherm HTC 03/16, using the profile recommended by DuPont® . The glass held well on the smaller window due to surface tension, as described earlier. Afterwards, a PMMA optical waveguide with a diameter of 750 µm and a numerical aperture of NA = 0.5 was glued in. It was then trimmed using a grinding machine and finished with a polishing paper . In order to provide a hermetic fluidic connection, two fluidic ports made of steel capillaries were inserted into the structure.The chip was manufactured using commercially available DuPontmax = 470 nm and a spectral half-width of Δλ1/2 = 35 nm, as well as a light sensor  for fluorescence measurement, with integrated optical filters and an analog to digital converter (ADC). The light sensor provides a signal from 4 canals, which correspond with light filters: clear (from 350 to 650 nm), blue , green , and red . All color filters have a Gaussian spectra. Therefore, the green filter introduces significant selectivity towards fluorescein emission spectra at λmax = 520 nm over LED excitation light.The microfluidic chip is placed in a base station, which is also manufactured in a LTCC technology. The base station has an indentation for a microfluidic chip for effortless positioning of optical paths and it contains a super bright LED  for analyte excitation, with an emission peak of λThe presented two-component LTCC-based microfluidic system has been already applied for the fluorescent detection of various chemical and biological agents ,123. BalMedical biosensors can diagnose health conditions, such as diabetes, cardiovascular issues, infectious diseases, and cancer. Increasingly, biosensors are also being used to achieve targeted therapies in precision medicine and increase the efficacy of drugs through pharmacogenomics.The current trend in POCT is inclined strongly towards smart devices equipped with mobile healthcare (mH) , which cMycobacterium tuberculosis has also been reported by Jing et al. [Moreover, over the last two decades, microfluidic technologies  have experienced a significant growth in applications in the field of diagnostics. Microfluidics-based technologies have shown promising applications in several of the main laboratory techniques, including blood chemistries, immunoassays, nucleic-acid amplification tests, and flow cytometry . Microflg et al. . Of the However, the realization of new POC diagnostic tools must overcome regulatory defiance. Many occurring microfluidic POC patterns have significant but unproved capability to improve global health. Regulatory procedures, despite being time-consuming, are relevant to assure the effectiveness and reliability of diagnostic tests.


Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to increased postnatal growth compared to that of term infants and are, therefore, susceptible to a higher risk of developing iron deficiency or iron deficiency anemia. Notwithstanding, excess iron could affect organ development during the postnatal period, particularly in premature infants that have an immature and undeveloped antioxidant system. It is important, therefore, to perform a review and analyze the effects of iron status on the growth of premature infants. This is a transversal descriptive study of retrieved reports in the scientific literature by a systematic technique. PRISMA  guidelines were adapted for the review strategy. The inclusion criteria for the studies were made using the PICO  model. Consequently, the systematic reviews that included studies published between 2008–2018 were evaluated based on the impact of iron status on parameters of growth and development in preterm infants. Iron is involved in many key cellular functions and processes in humans due to its role as an essential micronutrient. This ubiquitous mineral plays a critical role in growth and the development of the central nervous system. It is essential for energy metabolism, cell differentiation, and a host range of physiological processes for the normal functioning of the brain . In spitPreterm infants are prone to develop iron deficiency anemia (IDA) in the first 4 months of life due to lower iron stores at birth compared with term infants, rapid growth and iron losses. Most fetal iron is transferred from the mother during the third trimester of gestation. This transfer is interrupted by preterm birth, resulting in iron stores at birth being proportional to birth weight. Despite low iron stores at birth, growth velocity of premature infants is maximal at a postmenstrual age of 28–38 weeks, reflecting a particularly high iron need. The risk of IDA in preterm infants is further increased by frequent uncompensated iatrogenic phlebotomy losses . Initial evaluation should include a clinical history, to assess prematurity, low birth weight, diet, chronic diseases, family history of anemia, and ethnic background. A complete blood count is the most common initial diagnostic test used to evaluate for IDA, and this count allows for differentiating microcytic, normocytic, and macrocytic anemia based on the mean corpuscular volume (MCV). Ferritin measurement is the most sensitive test for diagnosing IDA, being a good reflection of total iron storage and is also the first laboratory index to decline with ID .Developmental outcomes are positively influenced by adequate nutrition early in life, revealing an improvement in neurodevelopment and cognitive abilities in preterm infants, for instance. During development, ID negatively affects the growth and functioning of multiple organ systems particularly the brain, skeletal muscle, heart and the gastrointestinal tract ,9,10,11.An excess of iron can affect organ development during the postnatal period. There is an association between iron overload, retinopathy of prematurity, and bronchopulmonary dysplasia. Non-protein bound iron mediates oxidative stress in the presence of poor antioxidant capabilities, and this condition initiates or potentiates the progression of these pathologies through generation of free radicals . ID and There is a high prevalence of preterm babies who have an increased risk of IDA, and there are no clinical consensuses or guidelines about the clinical benefits of iron supplementation and/or fortification that the hospitals should follow with this extremely vulnerable population. Therefore, it is relevant to evaluate the effects of ID or iron toxicity on the optimal development and function of the organs such as the brain in premature infants, ID and iron overload disorders during this period .Consequently, this systematic review performed an analysis of the influence and effects of iron on the hematological parameters, growth, and development of premature infants. Thus, the review also revealed a systematic literature evidence on the beneficial effects of iron supplementation in premature infants.Descriptive study of the articles retrieved using a systematic technique.The data used in this study were obtained from the consultation and direct access to the scientific literature collection in the following databases: Medlars International Literature Online (MEDLINE) via PubMed , The Cochrane Library Plus, SCOPUS (World’s largest abstract and citation database of peer-reviewed literature), Web of Science and Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS).A search strategy for electronic databases was developed with regard to information processing, from the Thesaurus study, Medical Subject Headings (MeSH) developed by the U.S. National Library of Medicine.The use of the following terms was considered appropriate: “Iron”, “Growth and Development”, and “Infant, Premature”, as well as descriptors as text in the title and summary record fields. A search equation was developed for use in the MEDLINE database, via PubMed, using boolean connectors, and then adapted to the rest of aforementioned data bases: (“Iron”(Mesh) AND “Growth and Development”(Mesh) AND “Infant, Premature”(Mesh)). The search was expanded to include “Anemia, Iron-Deficiency” (Mesh).The proposed criteria for the studies included in the review, considering the PICO  model  were: , as the calculated period of obsolescence  should be greater than 80% . In the Two independent reviewers extracted the data. To increase uniformity and reduce bias, a standardized data collection form was used by each reviewer. The reviewers made a consensus decision when there was a discrepancy. From each eligible study, the following information/data were extracted: first author, year of publication, journal, eligibility criteria, definition of premature or low-birth weight, number of participants, hematological data (hemoglobin (Hb), hematocrit (Ht), serum iron) before iron supplementation, iron supplement dose, duration of iron supplementation, hematological data after iron supplementation, growth status after iron supplementation, adverse effects of iron supplementation, and effects of iron on cognitive status.The final sample of studies for review was subsequently assessed by the authors  separatehttp://www.TREND-statement.org) that must be described in the publication. The TREND statement is specifically developed to guide standardized reporting of nonrandomized controlled trials. The TREND statement complements the widely adopted CONsolidated Standards Of Reporting Trials (CONSORT) statement developed for randomized controlled trials. This is a collective effort in promoting the idea that transparent reporting is valuable to improve research synthesis and advance evidence-based recommendations for best practices and policies. A point was assigned for each item featured. Meanwhile, if an item was not applicable, it did not score (a maximum score of 22). When an item was composed of several points, these points were evaluated independently, giving the same value to each of them, and subsequently an average was made , in such a way that in no case the score of one point per item could be exceeded. For each included study, a consensus was achieved after discussion of discrepancies. Non-randomized studies were assessed using the Transparent Reporting of Evaluations with Non-randomized Designs (TREND) statement , which cUpon thoroughly reviewing the data collection and statistical analysis of each included article, it became apparent that there was too much variation between these studies, and, therefore, it was not considered appropriate to conduct additional analysis such as a meta-analysis using the reported findings.J.M-F and J.D-C reviewed the articles independently, extracted relevant data from each included article, and assessed risk of bias. The Delphi List was carried out in the 5 randomized studies selected, while the TREND Checklist was used in the 9 non-randomized selected manuscripts. Any discrepancies in scoring were resolved by mutual discussion or through discussion with J.J.O. An overall risk of bias rating was assigned to each study based on the quality score.The Delphi List carried out in the selected manuscripts is provided in The above methodology resulted in a total description of search criteria and provided a total of 108 citations. The title and abstract of each report were reviewed by J.M.-F. and J.D.-C. to assess eligibility, and if the abstract or title was not described in enough detail, full reports were assessed to consider their inclusion. In this sense, all full-text reports for inclusion eligibility were independently assessed by J.M.-F. and J.D.-C. The level of agreement between the two researchers was high enough. The researchers resolved minor differences related to the inclusion of the reports by discussion. The potential lists of each relevant recovered article were scanned and four more articles were identified as possibly relevant. Duplicate manuscripts and those based on exclusion criteria and limits were removed. Thirty studies remained potentially eligible . SixteenThe summary of the most relevant characteristics of the randomized and non-randomized studies included are shown in Regarding the randomization, this review includes six randomized studies ,27,28,29Sample sizes ranged from 46 to 401 subjects. Among the total of 1743 participants included in the trials, 50.95% were men and 49.05% were women. One study did not specify the number of male and female participants . The ageAmong all included studies, a variety of different iron status parameters were investigated. Most of the studies analyzed Hb, serum ferritin (SF), serum iron, and total iron-binding capacity (TIBC). Neurological development was also studied to measure the developmental assessment scale and child behavior checklist questionnaire. Berglund et al.  followedAll of the studies included in the review assessed the iron status in preterm neonates to evaluate iron metabolism and requirements, supplying a large number of different measures. SF levels were reported in all the studies except Amin et al. , who meaTwo studies measured reticulocytes counts ,34, one p < 0.001) at an expected rate for the age of the population during the postnatal development of all infants, although these measurements were lower in preterm infants. The infants with iron depletion showed a lower birth weight than those without iron depletion. Lower birth weight and SF concentrations are independently associated with iron depletion at 6 weeks of age [In all studies that analyzed the weight, the length and head circumference of premature infants was lower than that of the term infants. As suspected, these measurements were lower in preterm infants when compared to term infants, although Yamada and Leone  showed as of age . A studys of age  showed as of age . On the s of age .In addition, a lower birth weight was found in infants born with iron overload compared to those with normal iron status and latent ID status (serum ferritin ˂76 ng/mL or ˂170.7 pmol/L) . Other sID was evaluated despite the different iron status indices used in the studies consulted. Most of the studies revealed that preterm or late preterm neonates usually featured a high risk of ID. p = 0.01). Moreover, ferritin levels were significantly lower (p = 0.006) those in the preterm appropriate for gestation group compared to the term appropriate for gestation infants. Serum iron also decreased in the preterm small for gestational age group compared to the preterm appropriate for gestation group (p = 0.002). Amin et al. [In this sense, indicators of iron status, including Hb levels and the prevalence rates of ID and IDA at 6 months, differed significantly in a dose-dependent manner between the intervention groups. Berglund et al.  found thn et al.  showed tp = 0.02). Hb and Ht decreased mainly in the late-preterm newborns (p < 0.001). At birth, differences between the two groups were observed only for Ht (p = 0.010), whereas at two months, more dramatic differences in both Hb (p = 0.020) and Ht (p < 0.001) were reported. Iron concentrations in the late-preterm infants were lower at term (p = 0.0034) and at one month post term (p < 0.001). TIBC showed lower levels when measured in the late-preterm infants at birth (p < 0.001). Transferrin saturation presented a similar pattern and was lower in late-preterm newborns at birth (p < 0.001). In a study conducted by de Waal et al. [p < 0.001). At the same time point, infant with ID did not show any differences in ZnPP/H levels compared with normal infants p = 0.223). In addition, a study conducted by Amin et al. [In this sense, Yamada and Leone , indicatl et al.  with pren et al.  revealedp = 0.005, p = 0.018, respectively). At the birth of preterm infants, SF levels were lower than those of full-term infants (p = 0.011), and the transferrin saturation of preterm infants did not differ between birth and 1 month after birth levels. Preterm infants showed a significant increase in prohepcidin levels (p = 0.011), a finding not shown in full-term infants.Conversely, others studies reported that there were no significant differences between preterm or term infants with regards to ID. Therefore, Molloy et al.  observedIron supplementation was established in 9 studies. Most of the studies supplied iron as elemental iron in ferrous sulfate chemical form, colloidal iron and ferrous succinate mixture while 3 studies did not specify the chemical form of iron supplement ,34,38. TIn the scientific literature, controversies abound on the necessity of t iron supplementation. Some studies showed a positive effect of iron supplementation and its role in preventing or treating ID. In a study with marginally low birth weight preterm or term infants, Berglund et al.  showed tIn contrast, other studies did not show any effect of iron supplementation. Saha et al.  suggesteUijterschout et al.  proposedOf the studies included in this systematic review, three directly investigated the effects of iron status on cognitive performance in premature infants. The techniques used to assess cognitive performance were noninvasive. p = 0.08).Berglund et al.  tested tp = 0.040) and “attention problems” (p = 0.022) subscales and a similar trend in all subscales except “withdrawn.” This study was reported to be the first showing a positive effect of early iron supplementation on neurobehavioral development beyond 2 years of age. This is another surprising result because ID impairs brain development and interferes with neurotransmitter function and biosynthesis, particularly with regard to dopamine and other monoamines. Another study by Berglund et al. , used thBerglund et al.  tested aIn general the results observed in the different studies of Berglund ,27,28,29Gupta et al.  evaluateThis review investigated the literature available about the iron status of premature infants and their growth and development. Moreover, it evaluated the effect of iron supplementation in this age group. Premature infants revealed a lower weight, length, and head circumference compared to term infants. The preterm infants with iron depletion had a lower birth weight than those without iron depletion. Iron depletion at 6 weeks of age was independently associated with lower birth weights together with lower SF concentrations . Low iroRegarding iron status, results from the studies analyzed showed the absence of consensus on how to define iron stores in preterm infants. SF measurement is the most widely used index to evaluate iron status and it was measured in all studies. Even so, SF is not considered the best iron status parameter by all the authors, because it changes over time and increases during infection and inflammation ,34,42,43Mukhopadhyay et al.  used ferIron has a crucial role in many metabolic pathways, especially in erythropoiesis and neurodevelopment . SpecifiAlthough, some studies did not find lower iron parameters in premature infants after birth, Molloy et al.  found thTaking into account iron status in preterm infants, it seems highly relevant to study the presence or absence of ID or IDA in this population. Premature infants have increased risk to develop ID, which is the most common micronutrient deficiency in the world , and alsDewey et al.  reportedAccording to these results and taking into account the importance of avoiding ID in this population, iron supplementation of preterm neonates seems vital because rapidly depleting inadequate iron stores cannot meet the iron requirement of enhanced erythropoiesis during this period. However, previous studies on iron supplementation in preterm infants have yielded conflicting results ,58. AlthIn contrast, Sankar et al.  did not Regarding the effect of iron supplementation on cognitive performance, Berglund et al.  evaluateBerglund et al.  did not Iron plays a crucial role in myelination, dendritic growth, and synaptogenesis. Therefore, ID could interfere with neurotransmitter function, mainly with regard to dopamine and other monoamines, which interestingly are closely associated with behavior . NonetheFinally, Gupta et al.  evaluateIn summary, the findings of this systematic review provide evidence that premature infants require iron supplementation in most of the cases and are susceptible to the development of ID or IDA, which could affect postnatal cognitive development and behavior. However, although ID impairs brain development due to its essential role in myelination, dendritic growth, synaptogenesis, and neurotransmitter function, motor, mental, and development parameters were not affected by iron supplementation in preterm neonates. Infants with iron depletion and overload showed a lower birth weight than those with a normal iron status. Taking into account these considerations, future research with more robust experimental designs and lower RoB are needed to achieve more solid conclusions.


The left ventricular ejection fraction (LVEF) and right ventricular function (RVF) were not associated with the primary outcome—HR 1.02  and 0.96  respectively. In patients admitted for ADHF, a high probability of PH as evaluated by echocardiography provided the highest independent prognostic value for mortality and readmission, whereas LVEF and RVF were not associated with prognosis. The identification of patients at high risk of PH by non-invasive measurement conveys important prognostic information and may guide management.The prognostic value of pulmonary hypertension (PH) estimated by echocardiography in unselected patients with acute decompensated heart failure (ADHF) is poorly studied. Between November 2014 and September 2018, 657 patients were recruited in a prospective registry of ADHF . The probability of pulmonary hypertension was based on European Society of Cardiology (ESC) guidelines for echocardiographic evaluation. The median survival without all-cause mortality or readmission was 7 months. During the median follow-up period of 15 months, there were 450 events including 185 deaths. In multivariate analysis, the hazard ratio (HR) of all-cause mortality or readmission for patients with a high probability of PH was 1.67 (95% CI 1.29–2.17,  Despite the availability of numerous therapeutic agents and advances in patient management, prognosis remains poor in heart failure (HF) ,2. AcuteClinicalTrials.gov NCT02444416). The study included patients with symptoms of heart failure based on the European Society of Cardiology (ESC) definition, such as dyspnea, ankle swelling and fatigue, accompanied by signs of heart failure such as elevated jugular venous pressure, pulmonary crackles or peripheral edema due to structural and/or functional cardiac abnormality ..7].p < 0.001) as compared to patients with a low or intermediate probability of PH (p = 0.84) and 0.96  respectively. Aortic stenosis and mitral stenosis were also associated with poor outcome, with HR’s of 1.5  and 2.37  respectively, as was a history of COPD , and chronic anemia . Of note, there was no significant difference in the proportion of patients with a history of COPD in the two PH groups (p < 001)  .p < 0.001), as compared to patients with a low or intermediate probability of PH (p = 0.38) and 1.07  respectively. Mitral stenosis and a history of COPD were also associated with poor outcome. These observed associations were similar when considering cardiovascular mortality alone.The probability of PH was also significantly associated with the secondary outcomes, including worse cardiovascular mortality or readmission. The hazard ratio of cardiovascular mortality or readmission in patients with a high probability of PH was 2.04 . In addition to the fact that LVEF was not significantly associated with outcome on multivariate analysis, this finding confirms the complex relationship between LVEF and prognosis [The close interaction between LVEF, the development of PH, and RVF is well described, and therefore it could be assumed that the prognostic value of each of these parameters would show a degree of overlap or co-linearity of association. Previous studies have only investigated selected HF patient populations; and furthermore, PH has only been assessed as an independent marker of prognosis only in specific cases such as reactive PH . Our sturognosis .The management of HF, and in particular ADHF, is complex and is well codified for HFrEF—less so for HFpEF. Estimation of prognosis is equally difficult and dependent on intrinsic cardiac properties as well as comorbidities. The clinical implications of this study are that the routine evaluation of PH and its incorporation into the care of patients admitted with ADHF may enable improved risk stratification, particularly for patients with a high probability of PH. Attention to valvular disease and specific therapies for PH such as the appropriate use of diuretics and monitoring may be important in this group.Our study has limitations. First, because of their observational nature, our findings are limited to association and not causality. Furthermore, despite multivariate analysis, there is residual confounding. Second, data collection on past medical history was based on medical records. In the case of COPD, cross-reference with pulmonary function results was not carried out, which may have led to the misclassification of this exposure risk. The strengths of our study are its prospective design, the consecutive inclusion of patients admitted with ADHF, and the use of robust clinical and biological inclusion criteria based on accepted guidelines and definitions for the identification of patients with HF ,8,34,35.In patients admitted for ADHF, a high probability of PH as evaluated by echocardiography, was the strongest predictor of all-cause mortality and hospital readmission. LVEF and RVF were not independently associated with prognosis. This suggests that the non-invasive estimation of PH in this setting provides important prognostic information, and its use in routine patient management could lead to improved clinical outcomes.


AbstractContemporary and historical bryozoan records were compiled to provide a comprehensive checklist of species in Scottish waters. The checklist comprises 218 species in 58 families, with representatives from each of the extant bryozoan orders. The fauna was relatively sparse compared to other regions for which bryozoan checklists were available e.g. New Zealand and Australia. Six non-indigenous bryozoan species from the Scottish seas region were included in the checklist. Baseline information on species distributions, such as that presented in this checklist, can be used to monitor and manage the impact of human activities on the marine environment, and ultimately preserve marine biodiversity. Bryozoa comprises approximately 6000 known/described extant species of filter feeding invertebrates that predominantly occur in the marine environment , order Phylactolaemataincertae sedis; class Stenolaemata, order Cyclostomatida). The order Cheilostomatida is the most diverse.The phylum ironment . There aAll bryozoans are clonal and the colonies can take many different forms including encrusting, erect and arborescent forms . The majBryozoans contribute to ecosystem functioning and services through the provision of three-dimensional structure and habitat for other species, and by serving as a food source for other marine species . Bryozoa2 of territorial seas  are denoted with an asterisk (*) in the checklist. Individual bryozoan records are provided in the Suppl. material The checklist is arranged phylogenetically for the higher-level taxa, with the families, genera, and species listed alphabetically. Taxonomy was checked against the World Register of Marine Species , and namBryozoa from the Scottish sea regions. A total of 218 species are included in the list, belonging to 128 different genera from 58 families. The Scottish records represent approximately 3.7% of the total number of bryozoan species known worldwide (n = 5869) . The most speciose bryozoan families in Scotland were the Calloporidae (13 species) and the Romancheinidae (13 species), which both contain mainly encrusting species.Table  = 5869) . There aNIS were identified as part of the Scottish fauna. These were Bugulinafulva , Bugulinasimplex , Bugulaneritina , Tricellariainopinata d’Hondt & Occhipinti Ambrogi, 1985, Fenestrulinadelicia Winston, Hayward & Craig, 2000, Schizoporellajaponica Ortmann, 1890. The Clyde sub-region contained the greatest number of NIS .Six PageBreakPageBreakPageBreakPageBreakPageBreakPageBreakPageBreakof focused taxonomic efforts in certain regions , Australia (n = 886), and the Mediterranean (n = 556) . Given S regions . Rosso a regions , which mNIS (NIS within the Clyde Sea region most likely represents the fact that the area is both a well-studied region and the location of a significant number of ports. As global shipping and aquaculture increase, along with climate change, it is expected that the number of invasive or non-indigenous bryozoans in the Scottish sea regions will increase in the future (As with other benthic marine invertebrates in Scotland, the bryozoan fauna includes NIS . The pree future .The estimate of bryozoan species number in Scotland, presented here, is likely to be conservative, since much of the offshore shelf areas and seamounts have not been fully explored. Estimates of the global number of bryozoan species yet to be discovered range from 2800–5200 . Given t


Our objective was to assess whether clusters of centers with similar peritoneal dialysis (PD) catheter related practices were associated with differences in the risk of technique failure.Patients on incident PD in French centers contributing to the French Language PD Registry from 2012 to 2016 were included in a retrospective analysis of prospectively collected data. Centers with similar catheter cares practices were gathered in clusters in a hierarchical analysis. Clusters of centers associated with technique failure were evaluated using Cox and Fine and Gray models. A mixed effect Cox model was used to assess the influence of a center effect, as explained by the clusters.Data from 2727 catheters placed in 64 centers in France were analyzed. Five clusters of centers were identified. After adjustment for patient-level characteristics, the fourth cluster was associated with a lower risk of technique failure (cause specific-HR 0.70, 95%CI 0.54–0.90. The variance of the center effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and clusters of centers in the mixed effect Cox model. Favorable outcomes were observed in clusters with a greater proportion of community hospitals, where catheters were placed via open surgery, first dressing done 6 to 15 days after catheter placement, and local prophylactic antibiotics was applied on exit-site.Several patterns of PD catheter related practices have been identified in France, associated with differences in the risk of technique failure. Combinations of favorable practices are suggested in this study. One of the main challenges of peritoneal dialysis (PD) is to ensure the sustainability of the technique. Peritonitis is a leading cause of technique failure , 2], , , 5], , , 8], , , 11], , . ConsequWe identified clusters of French PD centers that were grouped according to the proximity of their PD catheter related practices . We hypoThis was a retrospective study using data from the "catheter" section of the French Language Peritoneal Dialysis Registry (RDPLF) . Eighty-2), malnutrition , causal nephropathy, existence of diabetes and its type of treatment, and modified Charlson comorbidity index, which is the Charlson comorbidity index after excluding the age subscore, were extracted from the registry.Age, sex, weight, obesity , assistance for PD , type of administrative structure, and center size (number of catheters registered) were obtained from the database.Type of PD catheter, surgery technique, administration of antibiotic prophylaxis prior to catheter insertion, specialized surgeon for catheter placement, screening for nasal carriage of For each center, a practice was defined as being the center standard practice during the follow-up period whenever it was applied in 75% or more of the listed cases, from the individual data available in the registry.A hierarchical clustering analysis using Ward’s method was applied to determine five clusters of centers with similar practices . Each prThe primary outcome was PD technique failure, defined as a transfer to hemodialysis for longer than 2 months. Two events of interest were considered as secondary outcomes: first peritonitis episode for a given PD catheter, and technique failure due to peritonitis. A supplemental analysis was performed computing the risks for early or late technique failure (occurring respectively earlier or later than 3 months after the starting of PD). A composite outcome of technique failure and mortality was assessed to identify covariates potentially decreasing the risk of technique failure while increasing mortality.Categorical variables were described by their frequencies and percentages and continuous variables by their median and interquartile ranges. Differences of the distribution of practices among the clusters were evaluated using chi-squared tests. We examined for collinearity by assessing the generalized variance inflation factor.Kaplan-Meier survival curves were drawn, and log-rank tests were performed to determine whether the outcomes were different between the five clusters. Cox models were used to explore the association between the covariates and the events of interest: technique failure, first peritonitis episode, early and late technique failure. Considering the event technique failure due to peritonitis, other causes of technique failure would have been censored in a classical Cox model, overestimating the HR, so this event was not considered in the Cox model. Cause-specific HR with 95% confidence intervals (CI) were estimated. Regression splines were used to explore the effect of continuous variables and to choose their management in the models. Proportional hazard assumption was tested by visual inspection of Schoenfeld residual plots. Covariates were entered in the multivariate analysis when p < 0.20 in the bivariate analysis, the cluster covariate was entered a priori since it was the covariate of interest.To avoid overestimating hazard rate, a competing risk analysis was performed, accounting for the risk of death, renal transplantation and other causes of technique failure . The FinTo assess the relevance of the approach with clusters of practices, we used a hierarchical analysis. A mixed-effect Cox model was used to estimate the influence of the clusters on the center effect for the two events: technique failure, and first peritonitis episode. An empty Cox model (model 0) with center as random effect was fitted to estimate the random effect. Individual characteristics (level 1 covariates) were included in the model (model 1) to investigate whether the heterogeneity between centers was explained by the patient composition of the center. Cluster (level 2 covariates) was included in the model (model 2) to determine the magnitude of the clusters on the center effect. Model 1 and model 2 were compared with model 0 by analysis of variance (ANOVA). The proportional change in variance was calculated to estimate the contribution of the covariates in each model. Individual characteristics (level 1 covariates) were entered a priori in the multivariate analysis to improve the assessment of the center effect.th cluster of centers.We performed Cox and Fine and Gray analysis for each practice at the patients’ level to assess the isolated effect of practices on technique failure risk. Results were compared with those found in the 4The rate of missing data was < 3%. Given this very low rate, a complete case analysis was performed.Statistical analyses were performed with R 3.1.1  including the hclust, survival, cmprsk and coxme packages.Commission nationale de l’informatique et des libertés, agreement number 542 668) and fulfills the GDPR requests). This study took place within the framework of this authorization. All data analyzed were fully anonymized by the RDPLF, before we accessed them.The RDPLF provides an informative note to the patients, explaining the use made of their data, their rights to get an access to these data. Patients are informed of their right to oppose to the collection of their data without any consequence on their treatment. Nephrologists in the centers participating to the registry have the responsibility to give this note to any included patient, to obtain the patient’s signature for agreement, and to keep this agreement in the medical records. The RDPLF has the approval of the French National Ethics Committee  guidelines .Data concerning 2727 PD catheters placed in 2540 patients were included from 64 centers . The proThere were 10 academic hospitals, 33 community hospitals, 12 nonprofit centers, and 9 private centers . The numFive clusters of centers have been identified, according to the similarity of their PD catheter related practices . Table 1During the follow-up period, there were 604 technique failures, 755 peritonitis episodes occurring in 675 patients, and 81 cases of technique failure due to peritonitis. Survival curves are depicted on The absolute rate of survival free of technique failure censored for transplantation and death was 87% at one year during the follow-up period. In the bivariate analysis, covariates significantly associated with the risk of technique failure were sex, obesity, malnutrition, age, Charlson comorbidity index, and belonging to cluster number 4 in the Cox model, and obesity, malnutrition, age and belonging to cluster 4 in the Fine and Gray model . In the Of the 755 first episodes of peritonitis, 348 were due to Gram-positive cocci, 188 to Gram-negative bacilli, 18 to Gram-positive bacilli, 6 to fungi, and 195 to unidentified organism. The results of the bivariate analysis are given in Taking into account the competing events with a Fine and Gray model, cluster 2 was associated with a greater risk of technique failure due to peritonitis in the bivariate analysis  as in th−3 and p = 2·10−3, respectively). These results suggest that the clusters of practices explained a fifth of the center effect. Being treated in the fourth cluster was associated with a lower risk of technique failure  . The variance of the random effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and center clusters. Model 1 and model 2 were significantly different from model 0 according to ANOVA (p = 3·1050–1.00) .Compared with the first cluster, which was the reference, we found out that cluster 4 was protective against technique failure . In the centers from this cluster, there was a greater proportion of community hospitals, open surgery catheter placements, coiled catheters placed, use of local prophylactic antibiotics on exit-site, antiseptic use for dressing, and first dressing after catheter placement made between 5 and 14 days. On the other hand, there was fewer use of prophylactic antibiotic prior to catheter placement, and screening for nasal S. aureus presence. There was no difference on the covariates: use of assistance, PD modality, specialized surgeon for catheter placement .S. aureus, and surgeon experience.Results of the bivariate Cox and Fine and Gray models at the patient’s level are shown in Using an ascendant hierarchical analysis, we defined five clusters of centers with similar patterns of PD catheter related practices . Our stuOne should wonder why clusters of centers were used instead of studying the effect of each given practice separately. Randomized trials are mandatory to determine the best practices to propose to PD patients, but unfortunately, due to the large numbers of eligible practices, it is unlikely that evidence will be produced for each practice. Moreover, interactions may exist between practices and may have a synergic effect on the outcomes. The cluster analysis could help to identify association of practices that could influence positively the patient outcome. Furthermore, the method of clustering centers could allow implementation of quality improvement programs in group of centers, to prioritize the action at a nationwide level especially when practices are modifiable.Cluster identification could also lead to research about the effect of pattern of practices on the patient outcome. In support of this, in the pattern of practices of cluster 4, a greater proportion of patients received local prophylactic antibiotics on exit-site, a finding in line with the ISPD guidelines, . In the S. aureus, which have a sustained effect in time.We found that cluster 4 was protective against the risk of late technique failure, whereas there was no association with the risk of early technique failure. We can hypothesize from these results that the protective effect observed in cluster 4 was mainly due to the use of local prophylactic antibiotics on exit-site, the absence of antiseptic use for dressing, and the absence of screening for nasal Substantial variations in the peritonitis rate are reported between countries but also within countries 11]. On . On 11].Early peritonitis was associated with worse technique survival  in a 10-year single-center study in Taiwan . See et Few studies have focused on PD outcomes related to center-level characteristics. In a retrospective study analyzing 9100 episodes of peritonitis from the ANZDATA registry, Htay et al. showed that center-level characteristics substantially influenced PD peritonitis outcomes. Centers with more than 29% of dialysis patients treated with PD had higher odds of cured peritonitis (odds ratio (OR) 1.21, 95%CI 1.04–1.40) and lower odds of catheter removal , transfer to hemodialysis therapy  and peritonitis relapse/recurrence  . In anotPeritonitis risk was not different between the five clusters. However, cluster 2 was associated with a greater risk of technique failure due to peritonitis. This reflects that peritonitis outcomes are not uniform between the centers. Htay et al. found that the variation in odds of peritonitis cure across Australian centers was 66% lower after adjustment for center-level characteristics . Ways ofTaken together, these results argue that center experience and practices are more important than patient characteristics in determining major clinical outcomes in PD, such as technique failure and peritonitis outcome.Quality improvement programs have already proven their efficacy in PD care. The overall rate of technique failure was significantly reduced in Australia and New Zealand after a 2009 national peritonitis prevention program . Poor adConsidering every practice of a PD unit and assessing the coherence of the whole program could be a further step toward improvement. The “clusters method” that we propose here does not give a definitive answer to what the more suitable practices are, but it adds significant information by identifying centers where poor outcomes should be more prone to improve, by evaluating and changing practices.To our knowledge, this study is the first to propose a comparison of clinical outcomes among clusters of centers with similar practices. A large population of incident PD patients was included with very good quality data . Robust However, these strengths should be balanced against the study’s limitations, including the retrospective design and possibility of reporting bias. The use of registry data restricts the availability of clinical variables. Participation in the registry is voluntary, thus centers participating in the RDPLF may have more involvement in PD than other centers and may have different practices. Covariates declared in the registry, like specialization of the surgeon, were not defined in a standardized way, exposing to a declaration bias. The survival models used here do not allow handling for multiple events, which is a limitation considering the outcome peritonitis.In conclusion, clusters of centers with similar patterns of practices can be identified in France. These patterns of practices are associated with significantly different risks of technique failure. Belonging to a given cluster explained a significant part of the center effect associated with the risk of technique failure, and therefore combinations of profitable practices are suggested.S1 TableEarly technique failure is defining as occurring earlier than 3 months after the starting of PD. Late technique failure is defining as occurring later than 3 months after the starting of PD. Cs-HR: Cause specific hazard ratio; sd-HR: sub distribution hazard ratio; p: global p-value; GN: Glomerulonephritis; TIN: tubulointertitial nephritis; ADPKD: autosomic dominant polycystic disease; CCI: Charlson comorbidity index, *: p < 0.2; **: p < 0.05.(DOCX)Click here for additional data file.S2 TableCs-HR: Cause specific hazard ratio; sd-HR: sub distribution hazard ratio; GN: Glomerulonephritis; TIN: tubulointertitial nephritis; ADPKD: autosomic dominant polycystic disease; CCI: Charlson comorbidity index, *: p < 0.2; **: p < 0.05.(DOCX)Click here for additional data file.S3 TableHosp: hospital, CAPD: Continuous Ambulatory Peritoneal Dialysis. APD: Automated Peritoneal Dialysis. *: p-value < 0.05.(DOCX)Click here for additional data file.S1 FigX, eY, and eZ, corresponding to the longitude, latitude and altitude. In the space of practices, e1 may be the use of prophylactic antibiotic prior to catheter insertion, e2 the type of catheter placed in the center, and each ei a given practice. In this space of n-dimension, a metric is built and distances between centers are computed, allowing to gathering the centers according to their proximity in term of practice.In the geographical space, the dimensions are e(TIF)Click here for additional data file.S2 FigThe classes of references are: female for the sex, 2–3 for the modified Charlson comorbidity index, and cluster number 1 for the clusters of centers. CCI: modified Charlson Comorbidity Index, cs-HR: cause specific hazard-ratio, 95%CI: 95% confidence interval, sd-HR: subdistribution specific hazard-ratio.(PDF)Click here for additional data file.S3 FigThe classes of references are: diabetic nephropathy for the nephropathy, female for the sex, 18–39 years old for the age, and cluster number 1 for the clusters of centers. GN: glomerulopathy, TIN: tubulo interstitial nephropathy, ADPKD: Autosomic dominant polycystic kidney disease, cs-HR: cause specific hazard-ratio, 95%CI: 95% confidence interval, sd-HR: subdistribution specific hazard-ratio.(PDF)Click here for additional data file.S4 FigThe classes of references are: female for the sex, 18–39 years old for the age, diabetic nephropathy for the nephropathy, 2–3 for the modified Charlson comorbidity index, and cluster number 1 for the clusters of centers. GN: glomerulopathy, TIN: tubulo interstitial nephropathy, ADPKD: Autosomic dominant polycystic kidney disease, CCI: modified Charlson Comorbidity Index, cs-HR: cause specific hazard-ratio, 95%CI: 95% confidence interval, sd-HR: subdistribution specific hazard-ratio.(PDF)Click here for additional data file.S5 FigThe classes of references are: female for the sex, 18–39 years old for the age, 2–3 for the CCI, and cluster number 1 for the clusters of centers. CCI: modified Charlson Comorbidity Index, cs-HR: cause specific hazard-ratio, 95%CI: 95% confidence interval, sd-HR: subdistribution specific hazard-ratio.(PDF)Click here for additional data file.S6 FigThe classes of references are cluster number 1 for the clusters of centers. CCI: modified Charlson Comorbidity Index, cs-HR: cause specific hazard-ratio, 95%CI: 95% confidence interval, sd-HR: subdistribution specific hazard-ratio.(PDF)Click here for additional data file.


Background: Trust represents a complex emotion and interpersonal concept which assumes abandoning control over a given situation or set of circumstances, in turn yielding such control to another party. Advances in our knowledge of post-traumatic stress disorder and moral injury have underscored the need to more closely examine how trust stands to impact health outcomes in these disorders. The aim of the present study is to examine and identify relationships linking general trust with select health outcomes in a mixed sample of Veterans and Service members with a self-reported history of deployment to a combat theater and PTSD symptomatology.Methods: This study applied a cross-sectional methodology, surveying n = 427 participants recruited across six sites. This included 373 Veterans and 54 active duty Service members in the United States. Measures included demographic characteristics, combat exposure, general trust, post-traumatic stress disorder symptomatology, depressive/anxiety symptomatology, alcohol use, social involvement, religiosity, and physical health. Data were analyzed descriptively as well as using Pearson correlations, Student's t-test, and multivariate regression.Results: Several significant relationships were identified, indicating an inverse relationship between trust and PTSD, depressive, and anxiety symptomatology. Greater levels of trust were also significantly associated with increased social interaction and religiosity. Lastly, no significant associations were identified with either physical functioning or pain level.Conclusion: The findings suggest that trust is correlated with a variety of health outcomes in Veterans and Service members affected by combat-related PTSD. Additional, hypothesis-driven research, informed by longitudinal data, is needed to better understand how trust stands to impact health outcomes, including the development of strategies and intervention options for repairing trust. Developing and establishing trusting relationships remains essential to healthy human development. Trust represents a complex emotion and interpersonal concept which assumes abandoning control over a given situation or set of circumstances, in turn yielding such control to another party . An enhaThe value and importance of trust is especially well developed in the military, where the dynamic of military service pushes the issue of trust to the forefront –6. OperaA diminished capacity for trust usually falls under the rubric of general psychopathology and can be indicative of any number of clinical disorders. Understandings of how impacted trust stands to affect the health of Veteran and Service member populations have largely focused on samples affected by post-traumatic stress disorder (PTSD). In general terms, a diminished capacity for trust hampers access to social capital and supportive services, contributing to a downward spiral of increasing social isolation and difficulty accessing vital services . These uDisturbed trust is commonly encountered in cases of PTSD . DisturbAn emerging body of research into moral injury (MI) has also informed understandings of trust among Veterans and Service members. There is presently no clinical threshold or diagnostic standard to identify cases of MI. Further, there is no single, standardized definition of MI which would extend across clinical-therapeutic settings . Still, The aim of the present study is to examine and identify relationships linking general trust with select psychological, social, religious, and physical health outcomes in a mixed sample of Veterans and Service members in the United States. This study is unique in its use of a sample with a history of deployment to a combat zone as well as PTSD symptomatology. The present study adds to the extant literature by examining bivariate and multivariate relationships involving general trust, affording a more robust understanding of how trust stands to impact the health and well-being of Veterans and Service members with combat-related PTSD symptomatology. The findings could serve to inform future research aimed at developing interpersonal as well as organizational trust among combat Veterans and Service members, in addition to mitigating any adverse health effects resulting from having difficulty with general trust.n = 373 Veterans recruited from the Department of Veterans Affairs (VA) Medical Center (MC) in Durham , VA Greater Los Angeles Healthcare System , Charlie Norwood VAMC , Michael E. DeBakey VAMC , Audie L. Murphy VAMC . A sample of n = 54 active duty Service members were recruited through Liberty University . Only Veteran or active duty Service members, with a self-reported history of deployment to a combat theater, and exhibiting PTSD symptoms were included in this study.Participants for this cross-sectional study were recruited from six different sites. This included a sample of The data analyzed here were drawn from a larger study examining the psychometric properties of a measure of moral injury. A detailed methodology of this larger study has been published elsewhere . In brieWe applied several procedural remedies in an effort to mitigate any potential for common method bias . As partRespondents were asked their age, gender, race, education, and marital status. Respondents were also asked their religious affiliation, with the following answer options: Christian, Jewish, Hindu, Muslim, Buddhist, other, no affiliation, and atheist/agnostic.The 6-item General Trust Scale (GTS) was used to assess beliefs about the honesty and trustworthiness of others . The GTSDiagnostic and Statistical Manual, Fifth Edition (The PTSD Checklist for DSM-5 (PCL-5) is a 20-item measure assessing for the symptoms required for a PTSD diagnosis per criteria outlined in the  Edition , 42. The Edition , 44. ScoAll respondents self-reported either (a) deployment to a combat zone, without combat involvement or (b) deployment and combat involvement. For the purposes of the present study, this is taken to be indicative of combat-related symptomatology. A variety of deployment-related stressors have been associated with adverse mental health outcomes –47. RespThe 14-item Hospital Anxiety and Depression Scale (HADS) assesses for anxiety and depressive symptoms, each measured by seven items . The HADDaily alcohol intake was measured using a single item on a 4-point scale, ranging from “none” to “a lot (>6 drinks/day)”. For the purposes of data analysis, responses were dichotomized into (a) < 2 drinks/day and (b) >2 drinks/day.Respondents were asked to respond to two questions asking about (a) the quality of their relationships with spouse, children, and friends and (b) their level of involvement in community activities (other than religious group participation). Each was rated on a scale from 1  to 10 . The scores on the two items were summed to create a composite score ranging from 2 to 20, where higher scores are indicative of greater social involvement. In the present sample, α = 0.57.CI = 0.86–0.91) and test-retest reliability for the BIAC  were high. The scale has robust convergent, discriminant, and factor analytic validity (one factor explaining 94% of variance). In the present study, α = 0.90.The 10-item Belief into Action Scale (BIAC) is used to assess religious involvement , 51. ThiDifficulty engaging in physical activity level was assessed with a single item rated on a 0 to 10 scale . Current pain level was also assessed with a single question  likewise with ratings from 0 to 10 .If more than 50% of responses were left unanswered on the GTS, then such individual cases were removed from data analysis by list-wise deletion. In cases of missing items, if participants answered at least 50% of items on a given scale, the average of items answered was substituted for the missing item value. Missing values had to be substituted in 2.4% of GTS cases , 9.9% of PCL-5 cases, 8.3% of HADS cases, < 0.5% of the social involvement questions, and 5.9% of BIAC cases.t-test for comparison of trust scores across dichotomized categorical variables. Multivariate regression was used to examine the association between trust and mental, social-religious, and physical health states, controlling for demographic and military characteristics. First, all demographic and military characteristics were included in full multivariate models; second, only characteristics associated with the outcomes at p < 0.20 were included in final reduced models. Statistical significance was set at p < 0.05. SAS  was used for all analyses.Means (standard deviations) and frequency distributions were calculated to describe the sample. Associations between trust (6-item GTS) and demographic, military, social, religious, psychological, and physical health characteristics were examined using Pearson correlations for bivariate analysis of continuous variables and the Student's n = 7 (1.6%) individual cases were removed from data analysis owing to the omission of more than 50% of items on the GTS. The mean on the GTS was 35.1 (SD = 11.0) ranging from 6.0 to 54.0, with a median of 36.0 (n = 420). No significant difference on trust was found between Veterans and Active Duty Military on GTS scores . Those who were older, white Caucasian, more educated, deployed to combat theaters other than the Middle East , and deployed longer ago, all had higher trust scores , as well as less depression and lower levels of anxiety . Being non-White  was associated with greater PTSD severity, as was a history of deployment to the Middle East combat theater. When controlling for both of these factors, however, trust remained strongly and inversely associated with PTSD symptoms .Among demographic and military factors in full models that included all of these characteristics, only two were related to PTSD symptom severity .In the full model, greater depressive symptoms were associated with less education, being married, not being Christian, and not being actively involved in combat. Reduced models controlling for these demographic and military factors indicated that greater trust remained inversely related to depressive symptoms and was the strongest of all correlates .In the full model, greater anxiety was respectively reported by younger participants, married respondents, and those deployed to the Middle East. Controlling for these factors, greater trust remained inversely related to anxiety symptoms, and again, was the strongest and only significant inverse correlate .In the full model, social interaction was greater among those with more education, those who were actually involved in combat, and those who were not deployed to the Middle East . Again, greater trust remained significantly related to, and was the strongest predictor for, greater social interaction, even after controlling for these factors .In the full model, those who were older, non-White, with more education, and Christian reported higher scores on religious involvement. After controlling for these factors in the reduced model, greater trust remained significantly correlated with greater religiosity , relationships with significant others, and marital history. It is not uncommon for Veterans to have difficult pre-military family experiences . Enlistmn = 54; 13% of the sample). The present study did not assess for different types of trauma experienced by the sample. Lastly, all data was self-reported and not verified by official government and/or clinical records.The generalizability of the findings reported here and their interpretation is limited by several factors. This was a sample of convenience that involved volunteers who agreed to participate. As a cross-sectional study, it was impossible to determine causality . Participants were recruited from sites located primarily in the southern United States, so these results may not apply to Veterans and/or Service members more generally, nor do they take into consideration certain regional, cultural, or contextual influences which may not be present in other parts of the country. Future research should consider diversifying sample recruitment across multiple military, civilian, and geographic regions/settings. The dynamic governing trust among Service members is presumably different from that of Veterans. Any such bias would have been mitigated by the inclusion of only a small subsample of active duty Service members (Notwithstanding these limitations, the findings of this cross-sectional study provide an important degree of insight into the association between general trust and select health outcomes in a sample of Veterans and Service members with PTSD symptomatology. Understandings of how trust impacts health outcomes remain limited. Further, a paucity of evidence-based support options exist for building trust , 69. By This cross-sectional study sought to examine the relationship between general trust and select health outcomes in a mixed sample of Veterans and Service members with PTSD symptomatology. The findings suggest that trust is correlated with a variety of health outcomes in this group. Several significant relationships were identified between trust and clinical symptomatology of PTSD, depression, and anxiety, respectively. Trust was also associated with social interaction and religiosity. The findings suggest several avenues for additional research into how disturbed general trust impacts the health of Veterans and Service members with PTSD.This study was conducted in accordance with IRB and R&D Committee approval at Duke University as well as each data collection site. Prior to taking part, all participants gave written informed consent in accordance with the latest version of the Declaration of Helsinki.MK, DA, and HK: Contributed to writing article. HK: Data collection, database maintenance, data analysis.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Conclusions: Specific foot and general health-related QoL did not seem to be influenced by the foot arch height between high, normal and low feet arches heights. Nevertheless, further studies with higher sample sizes and matched-paired groups should be carried out.Background: Variations in the foot structure related with the high or low arch are identified common lower limb conditions, and it is supposed to be the effect on the quality of life (QoL) associated to foot health in adults. Here we aimed to determine the relationships between relatively high and low feet arches and QoL. Methods: A cross-sectional study was carried out. Among 138 adults enrolled in the study, 66 had a high arch, 21 had a low arch, and 51 were within the normal range. Changes related to the foot structure were analyzed using Area Calc version 2.6 software, and data obtained using the Foot-Health-Status-Questionnaire (FHSQ), whose domains were compared between foot arch groups by means of the one-way analysis of variance (ANOVA). Results: The results of the FHSQ comparison between the three groups within the sample population did not show any statistically significant difference ( The foot structure performs a key role in maintaining gait posture and balance. Therefore, most common variations in foot structure result in orthopedic conditions. Relatively high  or low (flatfoot or pes planus) medial longitudinal arches (MLAs) can result in musculoskeletal disorders affecting the lower limb and foot function ,2,3,4.Although the prevalence of foot structure problems has been reported as 46% to 80% in clinical practice and institutional settings ,6, how fFurthermore, the MLA is a complex structure, whose development is influenced by sex, type of footwear, use of shoes, walking barefoot, and body mass index (BMI), which might affect balance, flexibility, and stability in the foot ,8. A decThese changes in foot structure are associated with high cost, increased economic burden, and represent a serious public health concern because of the necessity of surgery and associated pain in other regions , as well as gait disturbance, risk of falling, and neurological alterations ,18,19.The relationship between QoL and foot health problems in adults has been poorly studied. Here we aimed to determine whether relatively high and low feet arches affect quality of life (QoL). We hypothesized that variations in foot structure would negatively affect QoL.A cross-sectional study was carried out. A total of 138 adults (18–64-year-old) part in this descriptive observational investigation carried out at a private podiatric medicine & surgery center where give a treat of foot and ankle disorders in the city of A Coruña, localized in the northwest of Spain during thirteen months, since February 2016–March 2017.Study participants were selected using a non-randomized and successive sampling technique. The mean age of the participants was 46.20 ± 11.37 years. The inclusion criteria were: >18-year-old; healthy adults without medical problems; and providing informed consent. The exclusion criteria were: Trauma in the lower limb, previous history of foot and limb surgery, neurological problems, autoimmune disease, loss of partial autonomy in daily life activities, pharmacotherapy, refusal to provide written consent, and inability to following the research guidelines.All podiatric medical examinations, measurements, and controls from recorded were made by an only the identical experienced medical podiatry using the same protocol. First, every subject was consulted about their medical status, including age, sex, actual and previous activities sporting, medical history and family history, and other conditions problems.The second step was an anthropometric assessment of features, which included height, weight, and BMI .Next, we determined the footprint of each participant using the photopodogram method . This toThe Institutional Research and Ethical Committee at the public University of Coruña approved this study (C.E. 27/2016). We adhered to the principles of the Declaration of Helsinki always and all participants provided informed consent before being enrolled in our research.http://www.fisterra.com/mbe/investiga/9muestras/9muestras2.asp) [The sample frame was analyzed using Clinical Epidemiology Research software, University of Coruña (as2.asp) . The stap = 0.5), and calculating a loss of healthy adults of 15%, we estimated that at least 114 subjects should be analyzed. A total of 138 adults people participated in this observational research.Considering a two-tailed test, an alfa level of 0.05, a desired might analysis of 95% with a beta level of 20%, a precision of 4% for proportion of 50%  for Windows was used to analyze the data. Categorical data were shown as frequencies and percentages, while quantitative data were described as mean and standard deviation (SD), according to the Shapiro-Wilk normality test. For the quantitative variables, between-group comparisons were performed by the one-way analysis of variance (ANOVA) for independent samples. The Chi-Squared test (χ2) was used for categorical data. FHSQ scores were obtained from the FHSQ Data Analysis Software . In all the analyses, p < 0.05  was considered statistically significant.The IBM software package IBM SPSS statistical software  were found between groups, except for sex distribution (p < 0.001).A total of 138 participants completed all research stages. Demographic and social characteristics are shown in (p > 0.05) and are shown in The results of the FHSQ comparison between the three groups within the sample population did not show any statistically significant difference Here we aimed to determine the relationship between having relatively high or low arched feet and QoL. This was achieved using a self-reported FHSQ in the adult population. Our alternative hypothesis has shown to be refused and the foot arch height  did not seem to be related to QoL impairments related to the foot and overall health.Previously to comparing the findings in this sections, it is worth showing that the various groups are meaningful in the adults and representative with anterior reports in the literature review that have associated with MLA with non-symptomatic foot , plantarBy definition, the volunteers with various degrees of MLA were classified according to the protocol designed by Cavanagh and Rodgers  related Thus, the relationship between FHSQ values showed similar findings with the high, normal or low arch of the participants. Despite there were not statistically significant differences between foot arch height, in the first section present lower scores in the footwear and foot health domains suggesting that adults could experience more foot problems in terms of can putting shoes and believe that their feet are in a poor state of health, without differences as regards MLA ,34,35,36Too, in the second section, this subjects presented lower points in the vigor may be related to restriction in the day a day to realizing sports activities and these findings are similar to other research.This study has several limitations. Notably, this research resulted many people from another place in the world. A random sampling design would have increased the power of this study. Also, the impact of other cultural factors and the economic status on MLA-related QoL could have been included. Lastly, although a sample size calculation was carried out, consecutive sampling bias should be considered, and a simple randomization sampling process would be better for future studies. Finally, due to our sample showed statistically differences in sex distribution and the number of participants in each group was not balanced, further studies with higher sample sizes and matched-paired groups should be carried out. Therefore, variations in foot structure related to MLA may be an important issue and requires further research to identify the best interventions for preventing and controlling limb problems in this population.Specific foot and general health-related QoL did not seem to be influenced by the foot arch height between high, normal and low feet arches heights. Nevertheless, further studies with higher sample sizes and matched-paired groups should be carried out.