Description: Background: Treatment-naive patients newly diagnosed with HIV occasionally present with low viral RNA of

Description: Background: In contrast with breast cancers (BCs) in other parts of the world, most previous studies reported that the majority of BCs in sub-Saharan Africa are estrogen-receptor (ER) negative. However, a recent study using the US SEER database showed that the proportion of ER-negative BC is comparable between US-born blacks and West-African born blacks but substantially lower in East African-born blacks, with over 74% of patients Ethiopians or Eritreans. In this paper, we provide the first report on the proportion of ER-negative BC in Ethiopia, and the relation to progesterone-receptor (PgR) status. Methods: We analysed 352 female patients with ER results available out of 1208 consecutive female BC patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. The influences of age, stage, and histology on the probability of ER-negative tumours were assessed by a log-linear regression model. Results: Of the 352 patients, only 35% were ER negative. The proportion of ER-negative tumours decreased with advancing age at diagnosis and was not affected by histology or stage. For age, the proportion decreased by 6% for each additional 5 years (stage-adjusted prevalence ratio PR = 0.94, 95% CI: 0.89-1.00). About 31% were ER- and PgR-negative, and 69% were ER- and/or PgR-positive. Conclusions: Contrary to most previous reports in other parts of sub-Saharan Africa, the majority of patients in Ethiopia are ER positive rather than ER negative. These findings are in line with low proportions of ER-negative BCs from East African immigrants within the SEER database, and they have clinical implications for management of BC patients in Ethiopia and other parts of sub-Saharan Africa where ER-status is not ascertained as part of routine management of the disease. Since the majority of patients showed ER-positive BC, Tamoxifen-therapy should be given to all patients even with unknown ER-status.

Description: Background: The relationship between psychological stress and interstitial cystitis/bladder pain syndrome (IC/BPS) has been well described. Even though there is some overlapping of symptoms between overactive bladder (OAB) and IC/BPS, there have been very few studies that specifically investigated the relationship between psychological stress and urinary symptoms in OAB patients who do not have pelvic pain. Here we examined the relationship between psychological stress levels and the severity of overactive bladder (OAB) symptoms. Methods: Patients diagnosed with OAB (n=51), IC/BPS (n=27), and age-matched healthy controls (n=30) participated in a case control study that inquired about their psychological stress levels using the perceived stress scale (PSS). PSS reported by the three patient groups were compared. Among OAB patients, their responses on the PSS was correlated to OAB symptoms using the following questionnaires: 1) international consultation on incontinence – urinary incontinence (ICIQ-UI), 2) international consultation on incontinence – overactive bladder (ICIQ-OAB), 3) OAB-q short form, 4) urogenital distress inventory (UDI-6), 5) incontinence impact questionnaire (IIQ-7), 6) urgency severity scale (USS), 7) numeric rating scales of urgency symptom, and 8) frequency symptom. Spearman’s correlation tests were performed to examine the relationship between psychological stress levels and the severity of OAB symptoms. Results: OAB patients reported psychological stress levels that were as high as IC/BPS patients (median 17.0 versus 18.0, p=0.818, Wilcoxon sum rank test), and significantly higher than healthy controls (17.0, versus 7.5, p=0.001). Among OAB patients, there was a positive correlation between perceived stress levels and urinary incontinence symptoms (ICIQ-UI, Spearman’s correlation coefficient=0.39, p=0.007), and impacts on quality of life (UDI-6, IIQ-7, OAB-q quality of life subscale; Spearman’s correlation coefficient=0.32, 0.31, 0.39, and p=0.028, 0.005, 0.029, respectively). No significant correlation was observed between perceived stress levels and urgency or frequency symptoms (ICIQ-OAB, USS, numeric ratings of urgency and frequency). Conclusions: OAB patients reported psychological stress levels that were as high as IC/BPS patients, and significantly higher than healthy controls. There was a positive correlation between perceived stress levels and urinary incontinence symptoms, and its impacts on quality of life among OAB patients.

Description: Background: With the advent of percutaneous coronary intervention, specifically the bare metal stent and subsequently, the drug-eluting stent, the scope of interventional cardiology has greatly increased. Aspirin, in combination with a thienopyridine is the present-day cornerstone of oral antiplatelet therapy after coronary artery stent placement. Continuing this chronic antiplatelet therapy, to mitigate a perioperative major adverse cardiac event, can be challenging and remains controversial in patients with a coronary artery stent undergoing non-cardiac surgery. We describe here the rationale for and successful use of an alternate approach to formulating local institutional management protocols for patients with a coronary artery stent, undergoing an elective surgical procedure.DiscussionA recent systematic review identified 11 clinical practice guidelines for the perioperative management of antiplatelet therapy in patients with a coronary stent who need non-cardiac surgery. However, there is significant variance and inadequacy with these current applicable professional society guidelines. Moreover, persistently variable success has been experienced in translating even well-grounded national clinical guidelines into local practice, including in the perioperative setting. Under the auspices of a broadly multidisciplinary institutional task force and applying the Consensus-Oriented Decision-Making model, we created two evidence-informed and local expert opinion-supported standardized clinical assessment and management plans for the preoperative management of antiplatelet therapy in patients with a coronary artery stent.SummaryPatient care can be optimized via evidence-based, yet locally developed and reiterative standardized clinical assessment and management plans for patients with coronary artery stents undergoing surgical procedures. Such standardized clinical assessment and management plans can result in greater consistency in care, providing a positive feedback loop in which the care plan itself can be continuously reevaluated, improved, and brought up to date with the most recent available data and knowledge.

Description: Background: The detection of HIV-1 p24 antigen in diagnostic tests relies on antibodies binding to conserved areas of the protein to cover the full range of HIV-1 subtypes. Using a panel of 43 different virus-like particles (VLPs) expressing Gag from clinical HIV-1 isolates, we previously found that some highly sensitive tests completely failed to detect p24 of certain VLPs, seemingly unrelated to their subtype. Here we aimed to investigate the reason for this failure, hypothesising that it might be due to single amino acid variations in conserved epitopes. Methods: Using amino acid alignment, we identified single amino acid variations at position 16 or 170 of p24, unique to those VLPs that failed to be detected in certain diagnostic tests. Through DNA-mutagenesis, these amino acids were changed to ones more commonly found at these positions. The impact of these changes on p24 detection was tested in commercial diagnostic tests as well as by Western Blot and ELISA, using epitope-specific antibodies.Results and ConclusionsChanging positions 16 or 170 to consensus amino acids restored the detection of p24 by the investigated diagnostic tests as well as by epitope-specific antibodies in Western Blot and ELISA. Hence, single amino acid changes in conserved epitopes can lead to the failure of p24 detection and thus to false-negative results. To optimise HIV diagnostic tests, they should also be evaluated using isolates which harbour less-frequent epitope variants.

Description: Background: Varied and fragmented care plans undertaken by different practitioners currently expose surgical patients to lapses in expected care, increase the chance for operational mistakes and accidents, and often result in unnecessary care. The Perioperative Surgical Home has thus been proposed by the American Society of Anesthesiologists and other stakeholders as an innovative, patient-centered, surgical continuity of care model that incorporates shared decision making. Topics central to the debate about an anesthesiology-based Perioperative Surgical Home include: holding the gains made in anesthesia-related patient safety; impacting surgical morbidity and mortality, including failure-to-rescue; achieving healthcare outcome metrics; assimilating comparative effectiveness research into the model; establishing necessary audit and data collection; a comparison with the hospitalist model of perioperative care; the perspective of the surgeon; the benefits of the Perioperative Surgical Home to the specialty of anesthesiology; and its associated healthcare economic advantages.DiscussionImproving surgical morbidity and mortality mandates a more comprehensive and integrated approach to the management of surgical patients. In their expanded capacity as the surgical patient's "perioperativist," anesthesiologists can play a key role in compliance with broader set of process measures, thus becoming a more vital and valuable provider from the patient, administrator, and payer perspective. The robust perioperative databases created within the Perioperative Surgical Home present new opportunities for health services and population-level research. The Perioperative Surgical Home is not intended to replace the surgeon's patient care responsibility, but rather leverage the abilities of the entire perioperative care team in the service of the patient. To achieve this goal, it will be necessary to expand the core knowledge, skills, and experience of anesthesiologists. Anesthesiologists will need to view becoming perioperative physicians as an expansion of the specialty, rather than an abdication of their traditional intraoperative role. The Perioperative Surgical Home will need to create strategic added value for a health system and payers. This added value will strengthen the position of anesthesiologists as they navigate and negotiate in the face of finite, if not decreasing fiscal resources.SummaryBroadening the anesthesiologist's scope of practice via the Perioperative Surgical Home may promote standardization and improve clinical outcomes and decrease resource utilization by providing greater patient-centered continuity of care throughout the preoperative, intraoperative, and postoperative periods.

Description: To understand and reduce the concomitant effects of trapping and handling procedures in wildlife species, it is essential to measure their physiological impact. Here, we examined individual variation in stress...

Description: Background: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid β-oxidation and a target disease of newborn screening in many countries.Case presentationWe report on two siblings with mild MCAD deficiency associated with a novel splice site mutation in the ACADM gene. The younger sibling was detected by newborn screening, while the older sister was missed, but diagnosed later on by genetic family testing. Both children were found to be compound heterozygous for the common c.985A 〉 G (p.K329E) mutation and a novel splice site mutation, c.600-18G 〉 A, in the ACADM gene. To determine the biological consequence of the c.600-18G 〉 A mutation putative missplicing was investigated at RNA level in granulocytes and monocytes of one of the patients. The splice site mutation was shown to lead to partial missplicing of the ACADM pre-mRNA. Of three detected transcripts two result in truncated, non-functional MCAD proteins as reflected by the reduced octanoyl-CoA oxidation rate in both patients. In one patient a decrease of the octanoyl-CoA oxidation rate was found during a febrile infection indicating that missplicing may be temperature-sensitive. Conclusions: Our data indicate that the c.600-18G 〉 A variant activates a cryptic splice site, which competes with the natural splice site. Due to only partial missplicing sufficient functional MCAD protein remains to result in mild MCADD that may be missed by newborn screening.

Description: A number of pathogens can cause severe destruction of the periodontal apparatus during the course of periodontitis. The aim of this work was the development of a diagnostic device for the use at the point-of-n...