70 research outputs found

    Status of institutional-level respectful maternity care:Results from the national Ethiopia EmONC assessment

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    Objective To assess the availability of an institutional-level respectful maternity care (RMC) index, its components, and associated factors. Methods A cross-sectional study design was applied to a 2016 census of 3804 health facilities in Ethiopia. The availability of an institutional-level RMC index was computed as the availability of all nine items identified as important aspects of institutional-level RMC during childbirth. Logistic regression analysis was used to identify factors associated with availability of the index. Results Three components of the institutional-level RMC index were identified: "RMC policy," "RMC experience," and "facility for provision of RMC." Overall, 28% of facilities (hospitals, 29.9%; health centers, 27.8%) reported availability of the institutional-level RMC index. Facility location urbanization (urban region), percentage of maternal and newborn health workers trained in basic emergency obstetric and newborn care, and availability of maternity waiting homes in health facilities were positively associated with availability of the institutional-level RMC index. Conclusion Only one in three facilities reported availability of the institutional-level RMC index. The Ethiopian government should consider strengthening support mechanisms in different administrative regions (urban, pastoralist, and agrarian), implementing the provision training for health workers that incorporates RMC components, and increasing the availability of maternity waiting homes

    Pattern of Recurrence after Curative Resection of Local (Stage I and II) Non-Small Cell Lung Cancer: Difference According to the Histologic Type

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    The aim of the present study was to evaluate the pattern of recurrence after complete resection of pathological stage I, II non-small cell lung cancer, especially according to the cell type. We reviewed the clinical records of 525 patients operated on for pathologic stage I and II lung cancer. The histologic type was found to be squamous in 253 and non-squamous in 229 patients. Median follow-up period was 40 months. Recurrences were identified in 173 (36%) of 482 enrolled patients; distant metastasis in 70%, distant and local recurrence in 11%, and local recurrence in 19%. Distant metastasis was more common in non-squamous than in squamous cell carcinoma (p=0.044). Brain metastasis was more frequently identified in non-squamous mthan in squamous cell carcinoma (24.2% vs. 7.3%. p=0.005). Multivariate analyses showed that cell type is the significant risk factor for recurrence-free survival in stage I and stage II non-small cell lung cancer. Recurrence-free survival curves showed that non-squamous cell carcinoma had similar risks during early periods of follow-up and more risks after 2 yr from the operation compared to squamous cell carcinoma. Pathological stage and histologic type significantly influence recurrence-free survival

    Impact of Parenchymal Tuberculosis Sequelae on Mediastinal Lymph Node Staging in Patients with Lung Cancer

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    Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli

    Radiographers' knowledge, attitudes and expectations of artificial intelligence in medical imaging

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    Introduction: Artificial intelligence (AI) is increasingly utilised in medical imaging systems and processes, and radiographers must embrace this advancement. This study aimed to investigate perceptions, knowledge, and expectations towards integrating AI into medical imaging amongst a sample of radiographers and determine the current state of AI education within the community. Methods: A cross-sectional online quantitative study targeting radiographers based in Europe was conducted over ten weeks. Captured data included demographical information, participants’ perceptions and understanding of AI, expectations of AI and AI-related educational backgrounds. Both descriptive and inferential statistical techniques were used to analyse the obtained data. Results: A total of 96 valid responses were collected. Of these, 64% correctly identified the true definition of AI from a range of options, but fewer (37%) fully understood the difference between AI, machine learning and deep learning. The majority of participants (83%) agreed they were excited about the advancement of AI, though a level of apprehensiveness remained amongst 29%. A severe lack of education on AI was noted, with only 8% of participants having received AI teachings in their pre-registration qualification. Conclusion: Overall positive attitudes towards AI implementation were observed. The slight apprehension may stem from the lack of technical understanding of AI technologies and AI training within the community. Greater educational programs focusing on AI principles are required to help increase European radiography workforce engagement and involvement in AI technologies. Implications for practice: This study offers insight into the current perspectives of European based radiographers on AI in radiography to help facilitate the embracement of AI technology and convey the need for AI-focused education within the profession

    Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen

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    The stable infection of host macrophages by Mycobacterium tuberculosis (Mtb) involves, and depends on, the attenuation of the diverse microbicidal responses mounted by the host cell. This is primarily achieved through targeted perturbations of the host cellular signaling machinery. Therefore, in view of the dependency of the pathogen on host molecules for its intracellular survival, we wanted to test whether targeting such factors could provide an alternate route for the therapeutic management of tuberculosis. To first identify components of the host signaling machinery that regulate intracellular survival of Mtb, we performed an siRNA screen against all known kinases and phosphatases in murine macrophages infected with the virulent strain, H37Rv. Several validated targets could be identified by this method where silencing led either to a significant decrease, or enhancement in the intracellular mycobacterial load. To further resolve the functional relevance of these targets, we also screened against these identified targets in cells infected with different strains of multiple drug-resistant mycobacteria which differed in terms of their intracellular growth properties. The results obtained subsequently allowed us to filter the core set of host regulatory molecules that functioned independently of the phenotypic variations exhibited by the pathogen. Then, using a combination of both in vitro and in vivo experimentation, we could demonstrate that at least some of these host factors provide attractive targets for anti-TB drug development. These results provide a “proof-of-concept” demonstration that targeting host factors subverted by intracellular Mtb provides an attractive and feasible strategy for the development of anti-tuberculosis drugs. Importantly, our findings also emphasize the advantage of such an approach by establishing its equal applicability to infections with Mtb strains exhibiting a range of phenotypic diversifications, including multiple drug-resistance. Thus the host factors identified here may potentially be exploited for the development of anti-tuberculosis drugs

    International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?

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    A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology–Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment

    Crystal Structures of Two Aminoglycoside Kinases Bound with a Eukaryotic Protein Kinase Inhibitor

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    Antibiotic resistance is recognized as a growing healthcare problem. To address this issue, one strategy is to thwart the causal mechanism using an adjuvant in partner with the antibiotic. Aminoglycosides are a class of clinically important antibiotics used for the treatment of serious infections. Their usefulness has been compromised predominantly due to drug inactivation by aminoglycoside-modifying enzymes, such as aminoglycoside phosphotransferases or kinases. These kinases are structurally homologous to eukaryotic Ser/Thr and Tyr protein kinases and it has been shown that some can be inhibited by select protein kinase inhibitors. The aminoglycoside kinase, APH(3′)-IIIa, can be inhibited by CKI-7, an ATP-competitive inhibitor for the casein kinase 1. We have determined that CKI-7 is also a moderate inhibitor for the atypical APH(9)-Ia. Here we present the crystal structures of CKI-7-bound APH(3′)-IIIa and APH(9)-Ia, the first structures of a eukaryotic protein kinase inhibitor in complex with bacterial kinases. CKI-7 binds to the nucleotide-binding pocket of the enzymes and its binding alters the conformation of the nucleotide-binding loop, the segment homologous to the glycine-rich loop in eurkaryotic protein kinases. Comparison of these structures with the CKI-7-bound casein kinase 1 reveals features in the binding pockets that are distinct in the bacterial kinases and could be exploited for the design of a bacterial kinase specific inhibitor. Our results provide evidence that an inhibitor for a subset of APHs can be developed in order to curtail resistance to aminoglycosides

    Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase.

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    Metformin is a first-line drug for the treatment of individuals with type 2 diabetes, yet its precise mechanism of action remains unclear. Metformin exerts its antihyperglycemic action primarily through lowering hepatic glucose production (HGP). This suppression is thought to be mediated through inhibition of mitochondrial respiratory complex I, and thus elevation of 5'-adenosine monophosphate (AMP) levels and the activation of AMP-activated protein kinase (AMPK), though this proposition has been challenged given results in mice lacking hepatic AMPK. Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin. We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment. We observe this during a metformin tolerance test and in a metformin-euglycemic clamp that we have developed. The antihyperglycemic effect of metformin in high-fat diet-fed diabetic FBP1-KI mice was also significantly blunted compared to wild-type controls. Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects
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