Spontaneous Dissection of Right Coronary Artery Manifested with Acute Myocardial Infarction

Spontaneous coronary artery dissection is a rare cause of acute ischemic coronary events and sudden cardiac death. It usually occurs in young women without traditional risk factors for coronary artery disease during pregnancy or postpartum period. However, it has also been reported in patients with atherosclerotic coronary disease. We present a case of spontaneous right coronary artery dissection in a 48-year male with recent myocardial infarction and previous percutaneous coronary intervention

Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations

The serotonin (5-HT) transporter (SERT) plays an important role in the termination of 5-HT-mediated neurotransmission by transporting 5-HT away from the synaptic cleft and into the presynaptic neuron. In addition, SERT is the main target for antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs). The three-dimensional (3D) structure of SERT has not yet been determined, and little is known about the molecular mechanisms of substrate binding and transport, though such information is very important for the development of new antidepressant drugs. In this study, a homology model of SERT was constructed based on the 3D structure of a prokaryotic homologous leucine transporter (LeuT) (PDB id: 2A65). Eleven tryptamine derivates (including 5-HT) and the SSRI (S)-citalopram were docked into the putative substrate binding site, and two possible binding modes of the ligands were found. To study the conformational effect that ligand binding may have on SERT, two SERT–5-HT and two SERT–(S)-citalopram complexes, as well as the SERT apo structure, were embedded in POPC lipid bilayers and comparative molecular dynamics (MD) simulations were performed. Our results show that 5-HT in the SERT–5-HTB complex induced larger conformational changes in the cytoplasmic parts of the transmembrane helices of SERT than any of the other ligands. Based on these results, we suggest that the formation and breakage of ionic interactions with amino acids in transmembrane helices 6 and 8 and intracellular loop 1 may be of importance for substrate translocation

A Steered Molecular Dynamics Study of Binding and Translocation Processes in the GABA Transporter

The entire substrate translocation pathway in the human GABA transporter (GAT-1) was explored for the endogenous substrate GABA and the anti-convulsive drug tiagabine. Following a steered molecular dynamics (SMD) approach, in which a harmonic restraining potential is applied to the ligand, dissociation and re-association of ligands were simulated revealing events leading to substrate (GABA) translocation and inhibitor (tiagabine) mechanism of action. We succeeded in turning the transporter from the outward facing occluded to the open-to-out conformation, and also to reorient the transporter to the open-to-in conformation. The simulations are validated by literature data and provide a substrate pathway fingerprint in terms of which, how, and in which sequence specific residues are interacted with. They reveal the essential functional roles of specific residues, e.g. the role of charged residues in the extracellular vestibule including two lysines (K76 (TM1) and K448 (TM10)) and a TM6-triad (D281, E283, and D287) in attracting and relocating substrates towards the secondary/interim substrate-binding site (S2). Likewise, E101 is highlighted as essential for the relocation of the substrate from the primary substrate-binding site (S1) towards the cytoplasm

Quality control and beam test of GEM detectors for future upgrades of the CMS muon high rate region at the LHC

Gas Electron Multipliers (GEM) are a proven position sensitive gas detector technology which nowadays is becoming more widely used in High Energy Physics. GEMs offer an excellent spatial resolution and a high particle rate capability, with a close to 100% detection efficiency. In view of the high luminosity phase of the CERN Large Hadron Collider, these aforementioned features make GEMs suitable candidates for the future upgrades of the Compact Muon Solenoid (CMS) detector. In particular, the CMS GEM Collaboration proposes to cover the high-eta region of the muon system with large-area triple-GEM detectors, which have the ability to provide robust and redundant tracking and triggering functions. In this contribution, after a general introduction and overview of the project, the construction of full-size trapezoidal triple-GEM prototypes will be described in more detail. The procedures for the quality control of the GEM foils, including gain uniformity measurements with an x-ray source will be presented. In the past few years, several CMS triple-GEM prototype detectors were operated with test beams at the CERN SPS. The results of these test beam campaigns will be summarised

Marjolin's ulcers at a university teaching hospital in Northwestern Tanzania: a retrospective review of 56 cases

Marjolin's ulcer is a rare but highly aggressive squamous cell cancer that is most often associated with chronic burn wounds. Although many individual case reports exist, no comprehensive evaluation of Marjolin's ulcer patients has been conducted in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our local setting and to identify predictors of outcome. This was a retrospective study of histologically confirmed cases of Marjolin's ulcer seen at Bugando Medical Centre over a period of 10-years between January 2001 and December 2010. Data were retrieved from patients' files and analyzed using SPSS computer software version 15.0 A total of 56 patients were studied. Male to female ratio was 2.1:1. Burn scars (89.3%) were the most common causative lesions of Marjolin's ulcer. The mean latent period between original injury and diagnosis of Marjolin's ulcer was 11.34 ± 6.14 years. Only 12.0% of the reported cases were grafted at the time of injury (P < 0.00). Most patients (48.2%) presented between one and five years of onset of illness. The lower limb (42.9%) was the most frequent site for Marjolin's ulcers. The median tumor size at presentation was 8 cm and the vast majority of patients (85.7%) presented with large tumors of ≥ 5 cm in diameter. Lymph node metastasis at the time of diagnosis was recorded in 32.1% of cases and distant metastasis accounted for 26.9% of cases. Squamous cell carcinoma (91.1%) was the most common histopathological type. Wide local excision was the most common surgical procedure performed in 80.8% of cases. Post-operative complication rate was 32.1% of which surgical site infection was the most common complication in 38.9% of patients. Local recurrence was noted in 33.3% of cases who were treated surgically. The mean length of hospital stay for in-patients was 7.9 ± 2.3 days. Mortality rate was 7.1%. According to multivariate logistic regression analysis, stage and grade of the tumor and presence of local recurrence were the main predictors of death (P < 0.001). Marjolin's ulcers are not rare in our environment and commonly occur in burn scars that were not skin grafted and were left to heal secondarily. A high index of suspicion is required in the management of chronic non-healing ulcers and all suspected lesions should be biopsed. Early recognition and aggressive treatment of Marjolin's ulcers and close follow-up are urgently needed to improve outcomes in our environment

Still too far to walk: Literature review of the determinants of delivery service use

BACKGROUND: Skilled attendance at childbirth is crucial for decreasing maternal and neonatal mortality, yet many women in low- and middle-income countries deliver outside of health facilities, without skilled help. The main conceptual framework in this field implicitly looks at home births with complications. We expand this to include "preventive" facility delivery for uncomplicated childbirth, and review the kinds of determinants studied in the literature, their hypothesized mechanisms of action and the typical findings, as well as methodological difficulties encountered. METHODS: We searched PubMed and Ovid databases for reviews and ascertained relevant articles from these and other sources. Twenty determinants identified were grouped under four themes: (1) sociocultural factors, (2) perceived benefit/need of skilled attendance, (3) economic accessibility and (4) physical accessibility. RESULTS: There is ample evidence that higher maternal age, education and household wealth and lower parity increase use, as does urban residence. Facility use in the previous delivery and antenatal care use are also highly predictive of health facility use for the index delivery, though this may be due to confounding by service availability and other factors. Obstetric complications also increase use but are rarely studied. Quality of care is judged to be essential in qualitative studies but is not easily measured in surveys, or without linking facility records with women. Distance to health facilities decreases use, but is also difficult to determine. Challenges in comparing results between studies include differences in methods, context-specificity and the substantial overlap between complex variables. CONCLUSION: Studies of the determinants of skilled attendance concentrate on sociocultural and economic accessibility variables and neglect variables of perceived benefit/need and physical accessibility. To draw valid conclusions, it is important to consider as many influential factors as possible in any analysis of delivery service use. The increasing availability of georeferenced data provides the opportunity to link health facility data with large-scale household data, enabling researchers to explore the influences of distance and service quality

The contribution of RCTs to quality management and their feasibility in practice

The randomized controlled trial (RCT) is generally accepted as the most reliable method of conducting clinical research. To obtain an unbiased evaluation of the effectiveness of spine surgery, patients should be randomly assigned to either new or standard treatment. The aim of the present article is to provide a short overview of the advantages and challenges of RCTs and to present a summary of the conclusions of the Cochrane Reviews in spine surgery and later published trials in order to evaluate their contribution to quality management and feasibility in practice. From the searches, 130 RCTs were included, 95 from Cochrane Reviews and systematic reviews, and 35 from additional search. No study comparing surgery with sham surgery was identified. The first RCT in spine surgery was published in 1974 and compared debridement and ambulatory treatment in tuberculosis of the spine. The contribution of RCTs in spinal surgery has markedly increased over the last 10 years, which indicates that RCTs are feasible in this field. The results demonstrate missing quality specifications. Despite the number of published trials there is conflicting or limited evidence to support various techniques of instrumentation. The only intervention that receives strong evidence is discectomy for faster relief in carefully selected patients due to lumbar disc prolapse with sciatica. For future trials, authors, referees, and editors are recommended to follow the CONSORT statement. RCTs provide evidence to support clinical opinions before implementation of new techniques, but the individual clinical experience is still important for the doctor who has to face the patient

Perspectives on care and communication involving incurably ill Turkish and Moroccan patients, relatives and professionals: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Our aim was to obtain a clearer picture of the relevant care experiences and care perceptions of incurably ill Turkish and Moroccan patients, their relatives and professional care providers, as well as of communication and decision-making patterns at the end of life. The ultimate objective is to improve palliative care for Turkish and Moroccan immigrants in the Netherlands, by taking account of socio-cultural factors in the guidelines for palliative care.</p> <p>Methods</p> <p>A systematic literature review was undertaken. The data sources were seventeen national and international literature databases, four Dutch journals dedicated to palliative care and 37 websites of relevant national and international organizations. All the references found were checked to see whether they met the structured inclusion criteria. Inclusion was limited to publications dealing with primary empirical research on the relationship between socio-cultural factors and the health or care situation of Turkish or Moroccan patients with an oncological or incurable disease. The selection was made by first reading the titles and abstracts and subsequently the full texts. The process of deciding which studies to include was carried out by two reviewers independently. A generic appraisal instrument was applied to assess the methodological quality.</p> <p>Results</p> <p>Fifty-seven studies were found that reported findings for the countries of origin (mainly Turkey) and the immigrant host countries (mainly the Netherlands). The central themes were experiences and perceptions of family care, professional care, end-of-life care and communication. Family care is considered a duty, even when such care becomes a severe burden for the main female family caregiver in particular. Professional hospital care is preferred by many of the patients and relatives because they are looking for a cure and security. End-of-life care is strongly influenced by the continuing hope for recovery. Relatives are often quite influential in end-of-life decisions, such as the decision to withdraw or withhold treatments. The diagnosis, prognosis and end-of-life decisions are seldom discussed with the patient, and communication about pain and mental problems is often limited. Language barriers and the dominance of the family may exacerbate communication problems.</p> <p>Conclusions</p> <p>This review confirms the view that family members of patients with a Turkish or Moroccan background have a central role in care, communication and decision making at the end of life. This, in combination with their continuing hope for the patient’s recovery may inhibit open communication between patients, relatives and professionals as partners in palliative care. This implies that organizations and professionals involved in palliative care should take patients’ socio-cultural characteristics into account and incorporate cultural sensitivity into care standards and care practices<it>.</it></p

In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model

Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4–8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success