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Objectives: In considering explanations for poor maternal and newborn health outcomes, many investigations have focused on the decision-making patterns and actions of expectant mothers and families, as opposed to exploring the 'supply side' (health service provider) barriers. Thus, we examined the health system factors impacting on access to and delivery of quality maternal and newborn healthcare in rural settings., Design: A semistructured qualitative study using face-to-face in-depth interviews with health professionals, and focus group sessions with community members, in eight project sites in two districts of Upper West Region, Ghana, was employed. Participants were purposively selected to generate relevant data to help address the study objective. The survey was guided by WHO standard procedures and Ghana Health Ministry's operational work plan for maternal and newborn care., Setting: Nadowli-Kaleo and Daffiama-Bussie-Issa districts in Upper West Region, Ghana., Participants: Two hundred and fifty-three participants were engaged in the study through convenient and purposive sampling: healthcare professionals (pharmacist, medical doctor, two district directors of health services, midwives, community health and enrolled nurses) (n=13) and community members comprising opinion leaders, youth leaders and adult non-pregnant women (n=240 in 24 units of focus groups)., Results: Results show significant barriers affecting the quality and appropriateness of maternal and neonatal health services in the rural communities and the Nadowli District Hospital. The obstacles were inadequate medical equipment and essential medicines, infrastructural challenges, shortage of skilled staff, high informal costs of essential medicines and general limited capacities to provide care., Conclusion: Implementation of the birth preparedness and complication readiness strategy is in its infancy at the health facility level in the study areas. Increasing the resources at the health provider level is essential to achieving international targets for maternal and neonatal health outcomes and for bridging inequities in access to essential maternal and newborn healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of the study was to investigate the expression of the tight junction protein occludin (encoded by OCLN gene) in human cervical cancer and its association with clinical features of patients., Materials and Methods: Sixty-one patients with cervical cancer were included in this study from June 30, 2015 to April 30, 2017. Immuno-histochemical assay was applied to examine the expression of occludin protein in 61 cervical cancer tissues and matched adjacent cancer normal tissues. The association of occludin protein expression with clinical pathology characteristics was analyzed., Results: Occludin protein was mainly expressed in cell membranes and cytoplasm of both the cervical cancer cell and the normal cells. The protein was manifested with brownish-yellow granules. In cervical cancer tissues, the positive rate of occludin protein was 77.05% (47/61), whereas, in adjacent normal tissues of the cancer, the positive rate was 96.72% (59/61). Therefore, the positive rate of occludin in cervical cancer tissues was significantly lower than that of the adjacent cancer tissues (P < 0.05). Occludin protein expression level was not significantly correlated with the age (P > 0.05), tumor size (P > 0.05), International Federation of Gynecology and Obstetrics staging (P > 0.05), pathological grades (P > 0.05), and lymph node metastasis (P > 0.05) of the patients., Conclusion: Occludin protein may contribute to the development of cervical cancer. However, it was not correlated with the clinical features., Competing Interests: There are no conflicts of interest.

Failure of embryo implantation is a major limiting factor in early pregnancy and assisted reproduction. Determinants of implantation include the embryo viability, the endometrial receptivity, and embryo-maternal interactions. Multiple molecules are involved in the regulation of implantation, but their specific regulatory mechanisms remain unclear. MicroRNA (miRNA), functioning as the transcriptional regulator of gene expression, has been widely reported to be involved in embryo implantation. Recent studies reveal that miRNAs not only act inside the cells, but also can be released by cells into the extracellular environment through multiple packaging forms, facilitating intercellular communication and providing indicative information associated with physiological and pathological conditions. The discovery of extracellular miRNAs shed new light on implantation studies. MiRNAs provide new mechanisms for embryo-maternal communication. Moreover, they may serve as non-invasive biomarkers for embryo selection and assessment of endometrial receptivity in assisted reproduction, which improves the accuracy of evaluation while reducing the mechanical damage to the tissue. In this review, we discuss the involvement of miRNAs in embryo implantation from several aspects, focusing on the role of extracellular miRNAs and their potential applications in assisted reproductive technologies (ART) to promote fertility efficiency.

Background: Despite decades of implementation of maternity healthcare programmes, including a focus on increasing the use of antenatal care (ANC) and concomitant birth preparedness and complication readiness (BPCR), the uptake of ANC continues to be below expectations in many developing countries. This has attendant implications for maternal and infant morbidity and mortality rates. Known barriers to ANC use include cost, distance to health care services and forces of various socio-cultural beliefs and practices. As part of a larger study on BPCR in rural Ghana, this paper reflects on the use of ANC in the study areas from rights-based and maternal engagement theoretical perspectives, with a focus on the barriers to ANC use., Methods: Mixed methods approach was adopted to collect data from 8 study communities from individual in-depth interviews with 80 expectant mothers and 13 health care professionals, and 24 focus groups comprising 240 community members. The qualitative data followed a thematic analytical method, while the quantitative data was analysed using descriptive statistics., Results: The average number of ANC visits were 3.34±1.292, and the majority of expectant mothers (71.3%) enrolled for ANC at the 8th week or later, with the longest delay recorded at the 6th month of gestation. Traditional norms significantly influenced this delay. Likewise, overall use of ANC during pregnancy was shaped by cultural factors related to perceptions of pregnancy, gender-based roles and responsibilities and concerns that ANC would result in an overweighed baby and culturally inappropriate delivery at a health care facility., Conclusion: Greater understanding of the sociocultural barriers to ANC is essential if proposed changes in community-specific health education programs are to facilitate early commencement and increased use of ANC.

Background: Maternal and neonatal morbidities and mortalities have received much attention over the years in sub-Saharan Africa; yet addressing them remains a profound challenge, no more so than in the nation of Ghana. This study focuses on finding explanations to the conditions which lead to maternal and neonatal morbidities and mortalities in rural Ghana, particularly the Upper West Region., Method: Mixed methods approach was adopted to investigate the medical and non-medical causes of maternal and neonatal morbidities and mortalities in two rural districts of the Upper West Region of Ghana. Survey questionnaires, in-depth interviews and focus group discussions were employed to collect data from: a) 80 expectant mothers (who were in their second and third trimesters, excluding those in their ninth month), b) 240 community residents and c) 13 healthcare providers (2 district directors of health services, 8 heads of health facilities and 3 nurses)., Result: Morbidity and mortality during pregnancy is attributed to direct causes such urinary tract infection (48%), hypertensive disorders (4%), mental health conditions (7%), nausea (4%) and indirect related sicknesses such as anaemia (11%), malaria, HIV/AIDS, oedema and hepatitis B (26%). Socioeconomic and cultural factors are identified as significant underlying causes of these complications and to morbidity and mortality during labour and the postnatal period. Birth asphyxia and traditional beliefs and practices were major causes of neonatal deaths., Conclusion: These findings provide focused targets and open a window of opportunity for the community-based health services run by Ghana Health Service to intensify health education and promotion programmes directed at reducing risky economic activities and other cultural beliefs and practices affecting maternal and neonatal morbidity and mortality.

The objective of this study is to present and test a new ultra-low-cost linear scan based tomography architecture. Similar to linear tomosynthesis, the source and detector are translated in opposite directions and the data acquisition system targets on a region-of-interest (ROI) to acquire data for image reconstruction. This kind of tomographic architecture was named parallel translational computed tomography (PTCT). In previous studies, filtered backprojection (FBP)-type algorithms were developed to reconstruct images from PTCT. However, the reconstructed ROI images from truncated projections have severe truncation artefact. In order to overcome this limitation, we in this study proposed two backprojection filtering (BPF)-type algorithms named MP-BPF and MZ-BPF to reconstruct ROI images from truncated PTCT data. A weight function is constructed to deal with data redundancy for multi-linear translations modes. Extensive numerical simulations are performed to evaluate the proposed MP-BPF and MZ-BPF algorithms for PTCT in fan-beam geometry. Qualitative and quantitative results demonstrate that the proposed BPF-type algorithms cannot only more accurately reconstruct ROI images from truncated projections but also generate high-quality images for the entire image support in some circumstances.

The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings.

Objective: This study analyses the ways in which curriculum reform facilitated student learning about professionalism., Methods: Design-based research provided the structure for an iterative approach to curriculum change which we undertook over a 3 year period. The learning environment of the Personal and Professional Development Theme (PPD) was analysed through the sociocultural lens of Activity Theory. Lave and Wenger's and Mezirow's learning theories informed curriculum reform to support student development of a patient-centred and critically reflective professional identity. The renewed pedagogical outcomes were aligned with curriculum content, learning and teaching processes and assessment, and intense staff education was undertaken. We analysed qualitative data from tutor interviews and free-response student surveys to evaluate the impact of curriculum reform., Results: Students' and tutors' reflections on learning in PPD converged on two principle themes--'Developing a philosophy of medicine' and 'Becoming an ethical doctor'--which corresponded to the overarching PPD theme aims of communicative learning. Students and tutors emphasised the importance of the unique learning environment of PPD tutorials for nurturing personal development and the positive impact of the renewed assessment programme on learning., Conclusions: A theory-led approach to curriculum reform resulted in student engagement in the PPD curriculum and facilitated a change in student perspective about the epistemological foundation of medicine.

Purpose: To investigate the role of readout-segmented echo-planar imaging using parallel imaging and a two-dimensional (2D) navigator (RESOLVE) in the evaluation of sinonasal lesions and to qualitatively and quantitatively compare the image qualities of single-shot echo-planar imaging (SS-EPI) and RESOLVE., Materials and Methods: Both sinonasal SS-EPI and RESOLVE images were acquired from 32 patients on a 3-T MR scanner. Image quality, lesion conspicuity and the distortions of the SS-EPI and RESOLVE images were qualitatively evaluated by two radiologists. Distortion was also quantitatively evaluated by comparing the distances between the same anatomic points on TSE-T1WI, TSE-T2WI, SS-EPI and RESOLVE images. The apparent diffusion coefficient (ADC) values, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the two DWIs were compared., Results: The comparisons of the qualitative scores indicated that RESOLVE significantly improved the image quality and lesion conspicuity and reduced the distortion of the sinonasal diseases. The orbit, skull base, temporal bone and upper neck were also better displayed on RESOLVE. Quantitative evaluations revealed that RESOLVE greatly reduced but did not completely remove the distortion. The ADC values of the sinonasal lesions on RESOLVE were lower than those on SS-EPI, whereas no differences were found in the brainstem. The SNR of RESOLVE was lower than that of SS-EPI. There were no differences in the CNRs of the two diffusion-weighted imaging (DWI) techniques., Conclusion: RESOLVE significantly improved the image quality for evaluations of sinonasal lesions by reducing the susceptibility artifacts, distortion and blurring compared with SS-EPI. RESOVLE offers more accurate ADC values of sinonasal lesions than SS-EPI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: It is widely accepted that all medical graduates should understand the uses and methods of rigorous research, with a need to promote research to graduates who will pursue an academic career. This study aimed to explore, identify and explain what motivates and demotivates medical students to do research., Methods: A convergent parallel mixed methods study was conducted. Cross-sectional quantitative survey data (n = 579) and qualitative semi-structured interview findings (n = 23) data were separately collected and analysed. Informed by Self-Determination Theory (SDT), quantitative and qualitative findings were integrated to develop a model for the factors associated with medical students' expressed motivation to do research, and related to clinical and research learning activities at different stages in an undergraduate medical program., Results: Only 7.5% of students had research experience prior to entering the program. Survey results revealed that students who had experienced exposure to the uncertainties of clinical practice through clerkships (Pre-Clinical (48%) vs Clinical Years (64%), p < 0.001), and a sense of achievement through supported compulsory research activities which were conducted as a team (Pre- Community Research (51%) vs Post-Community Research (66%), p < 0.001), were more likely to view future research activities positively. When integrated with qualitative findings using the three SDT domains of autonomy, competence and relatedness, eight major themes were identified: Self & Time, Career, Bureaucracy, Financial, Confidence, Clinical Relevance, Research as a Social Activity, and Personal Relevance. The findings suggest that motivation to do research is associated with increasing internalization of intrinsic motivators; in particular those associated with competence (Confidence) and relatedness (Clinical Relevance, Research as a Social Activity)., Conclusions: SDT is useful for understanding the motivation of individuals and how curriculum can be designed to optimise motivation. Study findings suggest that well supported compulsory research activities that incorporate group learning and elements of choice may promote motivation to do research, and potentially, careers in research, even in a research naive student body.

Complement regulatory proteins (CD55 and CD59) were known to be expressed in many tumors and tumor cell lines including colorectal carcinoma, and were proposed as immunotherapy targets, however whether knocking down of CD55 and CD59 will affect the sensitivity of HT-29 cells to chemotherapy drugs for example, 5-Fluorouracil and Oxaliplatin and their possible mechanisms haven't been studied. To address this question, SiRNAs targeting CD55 and CD59 were chemically synthesized and transfected into HT-29 cells by lipofectamine. HT-29 growth curves of CD55 and CD59 knockdown cells were detected by MTT assay, HT29 inhibition curves to chemotherapy drugs (5-Fu and Oxaliplatin) were also assayed, in addition, chemotherapy sensitivity changes of HT29 affected by CD55 and CD59 knockdown were equally detected. Complement mediated lysis was examined by calcein-AM. We found that silencing CD59 in HT-29 cells could significantly enhance their sensitivity to 5-FU (P < 0.05) and Oxaliplatin (P < 0.05), and significantly reduced their IC50 concentration. On the contrary, knocking down of CD55 could inhibit HT-29 growth (P < 0.05). Mechanisms included increasing apoptosis rate of HT-29 by CD59 knocking down and G1/G0 blocking by silencing CD55. Our results thus shed light on the novel mechanism of chemotherapy resistance and provide an alternative strategy to overcome the resistance problem., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Morphological observation and measurements of endocasts have played a vital role in research on the evolution of the human brain. However, endocasts have never been used to investigate how the human brain has evolved since the Neolithic period. We investigated the evolution of the human brain during the Holocene by comparing virtual endocasts from Beiqian site (a Neolithic Chinese site) and a sample of Chinese modern-day humans. Standardized measurements and indices were taken to provide quantification of the overall endocast shape, including the length, breadth, height, frontal breadth, and the ratio of frontal breadth to breadth, as well as the cranial capacity. We found that the height of the endocasts and cranial capacity have decreased between our two samples, whereas the frontal breadth and sexual dimorphism have increased. We argue that these changes can be caused by random genetic mutation and epigenetic change in response to changes in the environment., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic loss in the swine industry. Currently, there is no effective way to prevent PRRSV infection. Sodium tanshinone IIA sulfonate (STS), a natural compound derived from Salvia miltiorrhiza, was shown to possess anti-PRRSV activity, but the underlying mechanisms remain unclear. The objective of this study was to investigate the effect of STS on PRRSV-induced cell apoptosis and PRRSV N protein expression pattern., Methods: Relative quantification real-time PCR was used to evaluate the inhibition of STS on N gene expression. Simultaneously indirect immunofluorescence assay (IFA) and western blot were used to assess the effect on N protein expression. Apoptosis was analysed using fluorescence microscope with an annexin V-EGFP kit. The effect of STS on caspase-3 cleaving was assessed by western blot., Results: Our results showed that STS could inhibit viral N gene expression at both the messenger RNA stage and at the protein level in PRRSV-infected cells in a dose-dependent manner. In addition, STS could also rescue PRRSV-induced apoptosis., Conclusions: Our data suggest that STS may serve as a base compound for developing more effective drugs against PRRSV infection.

Platinum(II) metallointercalators of the type [Pt(I(L))(A(L))](2+), such as [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)](2+) (56MESS), are structurally different from cisplatin. This study, using a comparative transcriptomics approach, uncovered genomic expression patterns and molecular pathways that distinctively differentiated 56MESS and cisplatin in the eukaryote model organism Saccharomyces cerevisiae (yeast). Down-regulation of sulfur assimilation, cellular respiration, and energy metabolism were characteristics of 56MESS while up-regulation of these pathways and genes in cell cycle was the action of cisplatin. Furthermore, de novo purine biosynthesis and glycine metabolism were induced by 56MESS but suppressed by cisplatin. Different effects on intracellular concentrations of iron and copper were evident, with 56MESS more profoundly inducing genes controlling uptake of these ions than cisplatin. Finally, apart from 56MESS, additional metallointercalators including 56MEEN, 5MERR and 5MESS were subsequently identified to be more active in a cisplatin-resistant mouse leukaemia L1210cisR cell line than cisplatin, which provides multiple lead compounds for future drug development.

Unlabelled: Platinum-based DNA metallointercalators are structurally different from the covalent DNA binders such as cisplatin and its derivatives but have potent in vitro activity in cancer cell lines. However, limited understanding of their molecular mechanisms of cytotoxic action greatly hinders their further development as anticancer agents. In this study, a lead platinum-based metallointercalator, [(5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane)platinum(II)](2+) (56MESS) was found to be 163-fold more active than cisplatin in a cisplatin-resistant cancer cell line. By using transcriptomics in a eukaryotic model organism, yeast Saccharomyces cerevisiae, we identified 93 genes that changed their expressions significantly upon exposure of 56MESS in comparison to untreated controls (p ≤ 0.05). Bioinformatic analysis of these genes demonstrated that iron and copper metabolism, sulfur-containing amino acids and stress response were involved in the cytotoxicity of 56MESS. Follow-up experiments showed that the iron and copper concentrations were much lower in 56MESS-treated cells compared to controls as measured by inductively coupled plasma optical emission spectrometry. Deletion mutants of the key genes in the iron and copper metabolism pathway and glutathione synthesis were sensitive to 56MESS. Taken together, the study demonstrated that the cytotoxic action of 56MESS is mediated by its ability to disrupt iron and copper metabolism, suppress the biosynthesis of sulfur-containing amino acids and attenuate cellular defence capacity. As these mechanisms are in clear contrast to the DNA binding mechanism for cisplatin and its derivative, 56MESS may be able to overcome cisplatin-resistant cancers. These findings have provided basis to further develop the platinum-based metallointercalators as anticancer agents., Electronic Supplementary Material: The online version of this article (doi:10.1007/s12154-011-0070-x) contains supplementary material, which is available to authorized users.

Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure-activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and beta-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by (1)H and (195)Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using (1)H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.

The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB[8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB[6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB[6] of approximately 10(5) M(-1) was determined using (1)H NMR. Finally, the effect of CB[n] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CB[n] size, and whilst CB[7] and CB[8] generally decreased cytotoxicity, it was found that CB[6] increased the cyotoxicity of 5CLSS up to 2.5-fold.

The aim of this study was to explore the method for obtaining the thin sectional anatomy data of the adult temporal bone and study the fine structures using this method. Three fresh adult cadaveric heads were scanned with multi-slice computer tomography (MSCT) centered on petrous bones. The CT images of 0.6 mm were obtained by multi-planar reformation (MPR). The slices of 0.1 mm were shaved off the specimen in the axial direction with the numerical control milling machine after being embedded and frozen, pictures of which were taken by the digital camera and saved in the computer. The thin axial sectional anatomic structures of the intra-temporal were investigated and correlated with MPR images. Via the comparison, fifty micro-anatomic structures of the temporal bone that can't be delineated clearly or missed in the thick sections were evaluated. The anatomical details of the temporal bone can be clearly delineated in MSCT in sub-millimeter and were identical to those in sectional anatomy images. This method can supply anatomical details that had been missed or overlooked for imaging diagnosis and surgical anatomy.

In this paper, a compute aided diagnosis approach is proposed to physicians in the diagnosis of single-sided facial paralysis. This approach is different from the existing nine subjective and hand-performed international scales such as House-Brackman. For voluntary expressions of a patient, this approach used Pface, which stems from Dface, to measure the asymmetry between two sides of the face. The experiments on test subjects revealed that Pface could differentiate the paralysis stats and normal stats and has the ability of automatic grading facial paralysis. Moreover, Pface of specific face areas can be used in supervision of the rehabilitation process.