Πέμπτη 28 Ιουνίου 2018

In vivo identification of novel TGIF2LX target genes in colorectal adenocarcinoma using the cDNA-AFLP method

Publication date: Available online 28 June 2018
Source:Arab Journal of Gastroenterology
Author(s): Gholam Reza Mobini, Arefeh Ghafari, Saeid Amanpour, Roohollah Fateh, Mohammad Hossein Ghahremani, Samad Muhammadnejad, Ahmad Reza Dehpour, Abolfazl Akbari, Seyed Mojtaba Hoseiniharouni, Elham Kazemirad, Manzar Bolhassani, Mansour Heidari
Background and study aimsHomeobox-containing genes are composed of a group of regulatory genes encoding transcription factors involved in the control of developmental processes. The homeodomain proteins could activate or repress the expression of downstream target genes. This study was conducted to in vivo identify the potential target gene(s) of TGIF2LX in colorectal adenocarcinoma.MethodsA human colorectal adenocarcinoma cell line, SW48, was transfected with the recombinant pEGFPN1-TGIF2LX. The cells were injected subcutaneously into the flank of the three groups of 6-week-old female athymic C56BL/6 nude mice (n = 6 per group). The transcript profiles in the developed tumours were investigated using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique.ResultsThe real-time RT-PCR and DNA sequencing data for the identified genes indicated that the N-terminal domain-interacting receptor 1 (Nir1) gene was suppressed whereas Nir2 and fragile histidine triad (FHIT) genes were upregulated followed by the overexpression of TGIF2LX gene.ConclusionDownregulation of Nir1 and upregulation of Nir2 and FHIT genes due to the overexpression of TGIF2LX suggests that the gene plays an important role as a suppressor in colorectal adenocarcinoma.



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Socioeconomic Position and Reproduction: Findings from the Australian Longitudinal Study on Women’s Health

Abstract

Objective: To investigate the association of socioeconomic position (SEP) with reproductive outcomes among Australian women. Methods: Data from the Australian Longitudinal Study on Women's Health's (population-based cohort study) 1973–1978 cohort were used (N = 6899, aged 37–42 years in 2015). The association of SEP (childhood and own, multiple indicators) with age at first birth, birth-to-pregnancy (BTP) intervals and total number of children was analysed using multinomial logistic regression. Results: 14% of women had their first birth aged < 24 years. 29% of multiparous women had a BTP interval within the WHO recommendation (18–27 months). Women with a low SEP had increased odds of a first birth < 24 years: low (OR 7.0: 95% C.I. 5.3, 9.3) or intermediate education (OR 3.8: 2.8, 5.1); living in rural (OR 1.8: 1.5, 2.2) or remote (OR 2.1: 1.7, 2.7) areas; who found it sometimes (OR 1.8: 1.5, 2.2) or always difficult (OR 2.0: 1.6, 2.7) to manage on their income; and did not know their parent's education (OR 4.5: 3.2, 6.4). Low SEP was associated with having a much longer than recommended BTP interval. Conclusion: As the first Australian study describing social differences in reproductive characteristics, these findings provide a base for reducing social inequalities in reproduction. Assisting adequate BTP spacing is important, particularly for women with existing elevated risks due to social disadvantage; including having a first birth < 24 years of age and a longer than recommended BTP interval. This includes reviewing services/access to postnatal support, free family planning/contraception clinics, and improved family policies.



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Association between pre-operative biological phenotypes and postoperative pulmonary complications: An unbiased cluster analysis

BACKGROUND Biological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences. OBJECTIVE To assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes. SETTING Operating rooms of six hospitals in Europe and USA. DESIGN Secondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial. PATIENTS Adult patients scheduled for abdominal surgery who are at risk of PPCs. INTERVENTIONS Measurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury. MAIN OUTCOME MEASURES We applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes. RESULTS In total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-α (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml−1; P 

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RAD Sequencing and a Hybrid Antarctic Fur Seal Genome Assembly Reveal Rapidly Decaying Linkage Disequilibrium, Global Population Structure and Evidence for Inbreeding

Recent advances in high throughput sequencing have transformed the study of wild organisms by facilitating the generation of high quality genome assemblies and dense genetic marker datasets. These resources have the potential to significantly advance our understanding of diverse phenomena at the level of species, populations and individuals, ranging from patterns of synteny through rates of linkage disequilibrium (LD) decay and population structure to individual inbreeding. Consequently, we used PacBio sequencing to refine an existing Antarctic fur seal (Arctocephalus gazella) genome assembly and genotyped 83 individuals from six populations using restriction site associated DNA (RAD) sequencing. The resulting hybrid genome comprised 6,169 scaffolds with an N50 of 6.21 Mb and provided clear evidence for the conservation of large chromosomal segments between the fur seal and dog (Canis lupus familiaris). Focusing on the most extensively sampled population of South Georgia, we found that LD decayed rapidly, reaching the background level by around 400 kb, consistent with other vertebrates but at odds with the notion that fur seals experienced a strong historical bottleneck. We also found evidence for population structuring, with four main Antarctic island groups being resolved. Finally, appreciable variance in individual inbreeding could be detected, reflecting the strong polygyny and site fidelity of the species. Overall, our study contributes important resources for future genomic studies of fur seals and other pinnipeds while also providing a clear example of how high throughput sequencing can generate diverse biological insights at multiple levels of organisation.



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Genetic Analysis of Signal Generation by the Rgt2 Glucose Sensor of Saccharomyces cerevisiae

The yeast S. cerevisiae senses glucose through Snf3 and Rgt2, transmembrane proteins that generate an intracellular signal in response to glucose that leads to inhibition of the Rgt1 transcriptional repressor and consequently to derepression of HXT genes encoding glucose transporters. Snf3 and Rgt2 are thought to be glucose receptors because they are similar to glucose transporters. In contrast to glucose transporters, they have unusually long C-terminal tails that bind to Mth1 and Std1, paralogous proteins that regulate function of the Rgt1 transcription factor. We show that the C-terminal tail of Rgt2 is not responsible for its inability to transport glucose. To gain insight into how the glucose sensors generate an intracellular signal, we identified RGT2 mutations that cause constitutive signal generation. Most of the mutations alter evolutionarily-conserved amino acids in the transmembrane spanning regions of Rgt2 that are predicted to be involved in maintaining an outward-facing conformation or to be in the substrate binding site. Our analysis of these mutations suggests they cause Rgt2 to adopt inward-facing or occluded conformations that generate the glucose signal. These results support the idea that Rgt2 and Snf3 are glucose receptors that signal in response to binding of extracellular glucose and inform the basis of their signaling.



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Oxytocinergic modulation of brain activation to cues related to reproduction and attachment: Differences and commonalities during the perception of erotic and fearful social scenes

Publication date: Available online 28 June 2018
Source:International Journal of Psychophysiology
Author(s): Carina Sauer, Christian Montag, Martin Reuter, Peter Kirsch
In animal research, the neuropeptide oxytocin (OT) has been known for its role in reproduction and attachment for a longer time. There is strong evidence for an involvement of the mesolimbic dopaminergic system for these effects of OT. In contrast, human research rather concentrated on more human concepts of social cognition and behavior (e.g. trust or processing of fearful faces) and mainly focused on the amygdala as the main neurobiological substrate. To extend this view, we wanted to gain more insight into the neurobiological effects of OT in the context of reproduction and attachment in humans and compare these effects to its well-known effects on fear processing.In a double-blind placebo-controlled fMRI study, we investigated 55 healthy young men using intranasal OT administration. During fMRI, participants saw attachment-related erotic scenes and fearful social scenes.Over all participants, OT had a differential effect on processing of erotic and fearful scenes. While OT administration led to a relative increase of neural activation in mesolimbic structures during processing of erotic stimuli, it decreased amygdala activation for fearful stimuli. On the individual level, we observed significant positive correlations between OT induced activation changes across different brain regions and under different stimulus conditions.Our findings extend the already existing animal literature and provide evidence for a similar involvement of the mesolimbic dopaminergic system for OT effects in the context of reproduction and attachment in humans.



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The psychophysiology of stress and adaptation: Models, pathways, and implications

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Publication date: Available online 28 June 2018
Source:International Journal of Psychophysiology
Author(s): Brian M. Hughes, Patrick R. Steffen, Julian Thayer




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Oxytocin for learning calm and safety

Publication date: Available online 28 June 2018
Source:International Journal of Psychophysiology
Author(s): Monika Eckstein, Ana C. Almeida de Minas, Dirk Scheele, Ann-Kathrin Kreuder, René Hurlemann, Valery Grinevich, Beate Ditzen
The appropriate discrimination between safe and dangerous situations and the subsequent decrease of fear expression in the presence of safety signals are crucial for survival and mental health.Learning of safety associations is often studied in terms of fear extinction, that is re-learning of a previously conditioned stimulus which is now no longer positively associated with danger. Numerous studies investigated neurobiological processes of fear extinction and provide a valid picture of the underlying neural structures and endocrine processes involved.However, a formerly neutral conditioned stimulus (CS) can also predict the non-occurrence of an aversive, potentially dangerous, unconditioned stimulus (US) from the very beginning and thus can serve as a safety stimulus. This process has been termed safety learning. Although safety learning has been known for almost a century, there has been little research on its underlying neurobiological mechanisms, in contrast to the more prominent Pavlovian fear conditioning and fear extinction.In this review, we propose that the well-known action of the hypothalamic neuropeptide oxytocin (OXT) in the regulation of fear and stress responses is complementary to safety learning. We summarize the literature focused on OXT signaling and safety learning in animals and humans, from the first studies of fear extinction and conditioned inhibition of fear to the most recent findings in molecular and behavioral research on initial social safety stimuli. At the end, we discuss the application of OXT as a therapeutic agent to psychopathologies related to deficits in safety learning.



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Assisting hand function after spinal cord injury with a fabric-based soft robotic glove

Spinal cord injury is a devastating condition that can dramatically impact hand motor function. Passive and active assistive devices are becoming more commonly used to enhance lost hand strength and dexterity....

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Association between STAT4 polymorphisms and risk of primary biliary cholangitis: a meta-analysis

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Several studies reported that SATA4 (signal transducer and activator of transcription 4) polymorphisms were significantly associated with PBC susceptibility. In order to derive a more comprehensive estimation of the association between STAT4 and PBC risk, this meta-analysis was conducted. Thirteen eligible studies from 8 articles with a total number of 11,310 cases and 27,844 controls were included in this meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with fixed effects model or random effects model. The results showed statistically significant association between polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 and PBC risk under the allelic effect model (rs7574865, T vs. G, OR = 1.24, 95% CI 1.14–1.35; rs3024921, T vs. A, OR = 1.65, 95% CI 1.44–1.91; rs6752770, G vs. A, OR = 1.24, 95% CI 1.11–1.39; rs7601754, A vs. G, OR = 1.35, 95% CI 1.17–1.55; and rs10168266, T vs. C, OR = 1.31, 95% CI 1.22–1.41). Furthermore, the rs7574865 polymorphism was significantly associated with PBC risk under all genotype genetic models (dominant effect model: TT + TG vs. GG, OR = 1.43, 95% CI 1.19–1.71; recessive effect: TT vs. TG + GG, OR = 1.40, 95% CI 1.24–1.58; and co-dominant effect: TT vs. GG, OR = 1.67, 95% CI 1.37–2.02). The sensitivity analysis by omitting one study at a time showed that the results were stable. No publication bias was indicated from both Begg's test and Egger's weighted regression. This meta-analysis suggested that polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 were significantly associated with the risk of PBC.



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Correlation Between Pharyngeal Residue and Aspiration In Fiberoptic Endoscopic Evaluation of Swallowing – An Observational Study

Publication date: Available online 27 June 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yael Shapira-Galitz, Hagit Shoffel-Havakuk, Doron Halperin, MHA Yonatan Lahav
ObjectivesTo examine the correlation between pharyngeal residue severity and clearance to penetration-aspiration on FEES.DesignRetrospective cohort.SettingKaplan Medical Center dysphagia clinic.Participants110 patients visiting a dysphagia clinic between 2014-2016 undergoing FEES.InterventionsFEES were scored for penetration-aspiration with the penetration-aspiration scale (PAS), for residue severity using the Yale Pharyngeal Residue Severity Rating Scale, YPR-SRS. The numbers of swallows required to clear the pharynx were recorded. The first and the worst bolus challenge for each consistency (liquid, purée and solid) were analyzed.Main Outcome MeasuresYPR-SRS and number of clearing swallows were correlated with the PAS of the same bolus challenge.ResultsThe study population's mean age was 67±13.4 years; 54% were males (n=58). A significant correlation was found between the YPR-SRS and the PAS for all consistencies tested, in each anatomical site (vallecula or pyriform sinus) and for both the first and worst bolus challenge (p<0.001 for all). The correlation of residue with aspiration was stronger when vallecula and pyriform sinuses scores were summated (Pearson's correlation coefficient=0.573/0.631/0.446 for liquid/purée/solid for worst bolus challenge). Incorporating the number of clearing swallows to the YPR-SRS strengthened the correlation with PAS.ConclusionsResidue severity and clearance correlate with penetration/aspiration on FEES. The YPR-SRS can be applied to standardize description of residue in FEES and to aid in dysphagia evaluation.



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Characterization and development of EST-SSR markers to study the genetic diversity and populations analysis of Jerusalem artichoke ( Helianthus tuberosus L.)

Abstract

In recent years, Jerusalem artichoke has received widespread attention as a novel source of sugar, biofuel, and animal feed. Currently, only few gDNA-SSRs derived from sunflower were verified in the Jerusalem artichoke; therefore, it is particularly important to develop SSR primer markers that belonged to Jerusalem artichoke resources. Using EST data to develop EST-SSR markers is simple and effective. In order to understand the general characteristics of SSR markers in Jerusalem artichoke EST sequences and accelerate the use of SSR markers in Jerusalem artichoke research. This study used 40,370 sequenced unigene fragments and MISA software to identify SSR loci. The 48 pairs of EST-SSR primers assessed for the identification of 45 varieties of Jerusalem artichoke. Cluster, genetic diversity parameters and AMOVA analysis was conducted using the genetic similarity coefficient, revealing genetic differences between 48 genetic material. A total of 1204 SSR loci were identified with 13 different types of repeats, distributed among 1020 EST sequences, of which trinucleotide repeats were the most common, accounting for 38.21% of the total SSR loci. Among the 44 repeat motifs, AG/CT, AAG/CTT, and ATC/ATG motifs had the highest frequencies, accounting for 22.45, 14.71, and 7.84% of all motifs, respectively. From these sequences, 48 pairs of EST-SSR primers were designed, and 22 primer pairs for loci with high polymorphism were selected to analyze the genetic diversity of 45 Jerusalem artichoke germplasm sources. The results indicated that the variation range of the effective number of alleles for 22 primers ranged between 1.7502 and 4.5660. The Shannon's information index ranged between 0.6200 and 1.6423. The variation range of PIC ranged between 0.3121 and 0.6662 with an average of 0.5184. Cluster analysis was conducted using the genetic similarity coefficient, revealing significant genetic differences between Asian and European genetic material. Cluster analysis revealed a relationship between the genotypes and geographic origins of the Jerusalem artichoke. The results of AMOVA as well as the genetic identity and genetic distance in the Jerusalem artichoke population showed that there presented certain genetic heterogeneity in Jerusalem artichoke genetic structure of 45 samples from seven different geographic populations. The Jerusalem artichoke EST-SSR marker system established in this study provides an effective molecular marker system for future research focused on Jerusalem artichoke genetic diversity and the breeding of new varieties.



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Radionuclide observables of underwater nuclear explosive tests

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Publication date: December 2018
Source:Journal of Environmental Radioactivity, Volume 192
Author(s): Jonathan L. Burnett, Brian D. Milbrath
There remain technical challenges for an On-site Inspection (OSI) in the high seas environment, which gathers evidence of a violation of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). For terrestrial nuclear explosions, the radionuclide observables are well defined and States Parties have chosen 17 particulate radionuclides that allow discrimination from other nuclear events. However, an underwater nuclear explosion generates induced radionuclides from the neutron activation of seawater, which has the potential to interfere with the measurement of the radionuclide observables using gamma-spectrometry techniques. To understand these effects the inventory of OSI relevant (6.0 × 1016 Bq) and activation (1.6 × 1019 Bq) radionuclides has been calculated for a 1 kT underwater nuclear explosion. The activation products consist predominantly of 38Cl and 24Na, which decay to 5.56% and 0.0007% of their initial activity within 1 and 14 days. Monte Carlo techniques have been used to assess spectral interferences within this timeframe. It is demonstrated that during this period they do not interfere with the measurement of the existing radionuclide observables. Additionally, 24Na has been identified as useful for inspection purposes.



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Inequality and Innovation: Barriers and Facilitators to 17P Administration to Prevent Preterm Birth among Medicaid Participants

Abstract

Objectives Strategies to prevent preterm birth are limited. 17 Alpha-Hydroxyprogesterone Caproate (17P) injections have been shown to be effective, but the intervention is under-used. This mixed methods study investigates barriers and facilitators to 17P administration among Medicaid and CHIP participants enrolled in Strong Start for Mothers and Newborns, a federal preterm birth prevention program. Methods Twenty-seven awardees with more than 200 sites in 30 states, the District of Columbia, and Puerto Rico enrolled approximately 46,000 women in Strong Start from 2013 to 2016. Participant data, including data on preterm birth and 17P, was collected for each woman. Intensive interviews (n = 211) conducted with Strong Start program staff and providers (n = 314) included questions about 17P provision. Results Of women whose data included a valid response regarding 17P initiation, 3919 had a prior preterm birth and current singleton pregnancy; 14.95% received 17P. Barriers to 17P administration include late entry to prenatal care, administrative burden of preauthorization, cost risks to providers, limits in scope of practice for non-physician providers, and social barriers among participants. Facilitators for provision include streamlined work flows and the option of home administration. Conclusions for Practice A universal insurance authorization process could mitigate many barriers to 17P use. Providers need continuing education regarding the effectiveness of 17P, and expanding scope of practice for non-physician prenatal care providers would increase access. Targeted program interventions can help to overcome social barriers Medicaid participants face in accessing care. Streamlined work processes and the option of home health services are two effective program-based facilitators for providing 17P to a Medicaid population.



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De novo variants in GREB1L are associated with non-syndromic inner ear malformations and deafness

Abstract

Congenital inner ear malformations affecting both the osseous and membranous labyrinth can have a devastating impact on hearing and language development. With the exception of an enlarged vestibular aqueduct, non-syndromic inner ear malformations are rare, and their underlying molecular biology has thus far remained understudied. To identify molecular factors that might be important in the developing inner ear, we adopted a family-based trio exome sequencing approach in young unrelated subjects with severe inner ear malformations. We identified two previously unreported de novo loss-of-function variants in GREB1L [c.4368G>T;p.(Glu1410fs) and c.982C>T;p.(Arg328*)] in two affected subjects with absent cochleae and eighth cranial nerve malformations. The cochlear aplasia in these affected subjects suggests that a developmental arrest or problem at a very early stage of inner ear development exists, e.g., during the otic pit formation. Craniofacial Greb1l RNA expression peaks in mice during this time frame (E8.5). It also peaks in the developing inner ear during E13–E16, after which it decreases in adulthood. The crucial function of Greb1l in craniofacial development is also evidenced in knockout mice, which develop severe craniofacial abnormalities. In addition, we show that Greb1l−/− zebrafish exhibit a loss of abnormal sensory epithelia innervation. An important role for Greb1l in sensory epithelia innervation development is supported by the eighth cranial nerve deficiencies seen in both affected subjects. In conclusion, we demonstrate that GREB1L is a key player in early inner ear and eighth cranial nerve development. Abnormalities in cochleovestibular anatomy can provide challenges for cochlear implantation. Combining a molecular diagnosis with imaging techniques might aid the development of individually tailored therapeutic interventions in the future.



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Effects of Ethnic Identity on the Relationship Between Mental Health and Perceived Discrimination Among Ethnic Return Migrants: The Case of Korean Chinese Return-Migrated to South Korea

Abstract

This study examined the relationship among mental health, perceived discrimination and ethnic identity among Korean Chinese (Joseonjok) who have return-migrated to South Korea. A survey was conducted with 399 Joseonjok adults (≥ 19 years) residing in the capital city Seoul or nearby. Depression was measured using the (self-report) Center for Epidemiologic Studies Depression Scale-Korean (CES-D-K) version (n = 292, mean age = 42.6, female = 56.5%). Perceived discrimination and ethnic identity were assessed with single-item questions. The mean CES-D-K total score was 9.3 (SD = 8.4) and 20.6% had clinical depression (cut-off score: 16). Perceived discrimination was positively associated with CES-D-K scores (regression coefficient = 2.09, p = 0.04). This association was stronger in those identifying themselves more strongly as 'Korean' than 'Chinese'. Discrimination by 'co-ethnic hosts' can have a greater impact on mental health among those ethnic return migrants with a stronger ethnic identity. More efforts are needed to help them better integrate into South Korean society.



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Barriers Faced by the Health Workers to Deliver Maternal Care Services and Their Perceptions of the Factors Preventing Their Clients from Receiving the Services: A Qualitative Study in South Sudan

Abstract

Objective The study objective was to explore challenges and barriers confronted by maternal and child healthcare providers to deliver adequate quality health services to women during antenatal care visits, facility delivery and post-delivery care. Methods We conducted 18 in-depth-interviews with maternal and child health professionals including midwives/nurses, trained traditional birth attendants (TBAs), gynecologists, and pediatricians in three public health facilities in Juba, South Sudan. We purposively selected these health professionals to obtain insights into service delivery processes. We analyzed the data using thematic analysis. Results Limited support from the heath system, such as poor management and coordination of staff, lack of medical equipment and supplies and lack of utilities such as electricity and water supply were major barriers to provision of health services. In addition, lack of supervision and training opportunity, low salary and absence of other forms of non-financial incentives were major elements of health workers' de-motivation and low performance. Furthermore, security instability as a result of political and armed conflicts further impact services delivery. Conclusions for Practice This study highlighted the urgent need for improving maternal and child healthcare services such as availability of medical supplies, equipment and utilities. The necessity of equal training opportunities for maternal and child healthcare workers at different levels were also stressed. Assurance of safety of health workers, especially at night, is essential for providing of delivery services.



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