Miracle-dz/UniFAR-FTUs huggingface dataset:
InfectionActivation of Invariant NKT Cells during Antigen-Dependent versus -Independent

CD1d-reactive invariant NKT cells (iNKT) play a vital role in determining the characteristics of immune responses to infectious agents. Previous reports suggest that iNKT cell activation during infection can be: 1) solely driven by cytokines from innate immune cells, 2) require microbial Ag, or 3) require self-Ag. In this study, we examined the role of Ag receptor stimulation in iNKT cells during several bacterial and viral infections. To test for Ag receptor signaling, Nur77 gfp BAC transgenic mice, which upregulate GFP in response to Ag receptor but not inﬂammatory signals, were analyzed. iNKT cells in the reporter mice infected with mouse CMV produced IFN- g but did not upregulate GFP, consistent with their reported CD1d-independent activation. However, two bacteria known to produce lipid Ags for iNKT cells induced GFP expression and cytokine production. In contrast, although Salmonella typhimurium was proposed to induce the presentation of a self-lipid, iNKT cells produced IFN- g but did not upregulate GFP postinfection in vivo. Even in CD1d-deﬁcient hosts, iNKT cells were still able to produce IFN- g after S. typhimurium infection. Furthermore, although it has been proposed that endogenous lipid presentation is a result of TLR stimulation of APCs, injection of different TLR agonists led to iNKT cell IFN- g but not increased GFP expression. These data indicate that robust iNKT cell responses to bacteria, as well as viruses, can be obtained in the absence of antigenic stimulation. The Journal of Immunology , 2014, 192: 000–000.
Evaluating a counselling strategy for diagnostic WES in paediatric neurology: an exploration of parents' information and communication needs

As whole exome sequencing (WES) is just starting to be used as a diagnostic tool in paediatric neurology for children with a neurological disorder, and patient experiences and preferences with regard to counselling are relatively underexplored. This article explores experiences and preferences of parents with pre‐test and post‐test counselling in a trial that uses WES for diagnostics. Second, it maps information and communication needs which exceed the counselling protocol, in order to acquire insight into how it can be improved. Data were gathered through in‐depth interviews with parents of 15 children who were included in the trial. Information and communication needs of parents differed from the protocol with respect to (i) the type and amount of information provided about WES research, (ii) incidental findings, (iii) communication about progress of the study, and (iv) the communication of the results. Furthermore, parents preferred to have more of a communicative exchange with health care providers about their daily struggles and concerns related to their life with a diseased child and wanted to know how a diagnosis could offer help. There are different ways to meet parental needs, but we suggest that assigning a case manager might be a helpful option that deserves further exploration.
Evolving side effect machines to measure distances between DNA promoter sequences

Side Effect Machines are tools for extracting numeric features from alphabetic sequences. They have been used successfully on many DNA sequence classification tasks. This paper continues development of a new type of application for them, the creation of a distance measure between DNA sequences. The application problem is to find distances between promoter sequences of genes. These promoter sequences contain potentially dozens of short sequence motifs to which transcription factors bind. Finding relationships between promoter sequences has been addressed computationally in the past by looking for these sequence motifs. The method presented here has the potential to take into account not just individual motifs, but the entire genomic landscape. It leverages data on transcription factor binding sites determined with biological experiments on yeast and fruit flies to develop useful features.
Primary intraosseous squamous cell carcinoma arising in an odontogenic cyst: a clinicopathologic analysis of 116 reported cases.

PURPOSE To review the literature on primary intraosseous squamous cell carcinoma (PIOSCC) associated with odontogenic cyst. METHODS All well-documented cases of PIOSCC published between 1938 and 2010 were collected. Only cases of PIOSCC arising from the lining of an odontogenic cyst, including the keratocystic odontogenic tumor, were selected. Age, sex, signs and symptoms, affected jaw, cyst type, treatment, histopathology, and outcome were recorded. RESULTS The mean age was 60.2 years (range 1.3-90). There were 80 (69%) men and 36 (31%) women. Mass and pain were the most common presenting symptoms. The mandible was affected in 92 (79%) patients and the maxilla in 24 (21%). It was a residual/radicular cyst in 70 (60%) patients and a dentigerous cyst or a keratocystic odontogenic tumor in the remaining 40%. The histopathology was well-differentiated SCC in 53 (46%) patients and moderately differentiated SCC in 47 (40%) patients. Fifty-three (46%) patients were treated with surgery alone and 44 (38%) with surgery and radiotherapy. Fifty-eight (62%) patients survived 2 years and 36 (38%) survived 5 years. CONCLUSION PIOSCC has a predilection for men (M/F ratio of 2.22:1), affects mainly adults in their 6-8th decades, occurs most frequently (79%) in the mandible, and is associated mainly with a residual/radicular cyst. Histologically, the well-to-moderately differentiated SCC was the most common. Surgery alone or combined therapy of surgery and radiation was the most common approach. The prognosis is 62% surviving 2 years and 38% 5 years.
Patient Training for Functional Use of Pattern Recognition–Controlled Prostheses

ABSTRACT Pattern recognition control systems have the potential to provide better, more reliable myoelectric prosthesis control for individuals with an upper limb amputation. However, proper patient training is essential. We begin user training by teaching the concepts of pattern recognition control and progress to teaching how to control, use, and maintain prostheses with one or many degrees of freedom. Here, we describe the training stages, with relevant case studies, and highlight several tools that can be used throughout the training process, including prosthesis-guided training—a self-initiated, simple method of recalibrating a pattern recognition–controlled prosthesis. Prosthesis-guided training may lengthen functional use times, potentially increasing prosthesis wear time. Using this training approach, we anticipate advancing pattern recognition control from the laboratory to the home environment and, finally, realizing the full potential of these control systems.
Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides ‘proof of principle’ for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia.
Abnormal Cardiac Structure and Function in Mice Expressing Nonphosphorylatable Cardiac Regulatory Myosin Light Chain 2*

A role for myosin phosphorylation in modulating normal cardiac function has long been suspected, and we hypothesized that changing the phosphorylation status of a cardiac myosin light chain might alter cardiac function in the whole animal. To test this directly, transgenic mice were created in which three potentially phosphorylatable serines in the ventricular isoform of the regulatory myosin light chain were mutated to alanines. Lines were obtained in which replacement of the endogenous species in the ventricle with the nonphosphorylatable, transgenically encoded protein was essentially complete. The mice show a spectrum of cardiovascular changes. As previously observed in skeletal muscle, Ca2+sensitivity of force development was dependent upon the phosphorylation status of the regulatory light chain. Structural abnormalities were detected by both gross histology and transmission electron microscopic analyses. Mature animals showed both atrial hypertrophy and dilatation. Echocardiographic analysis revealed that as a result of chamber enlargement, severe tricuspid valve insufficiency resulted in a detectable regurgitation jet. We conclude that regulated phosphorylation of the regulatory myosin light chains appears to play an important role in maintaining normal cardiac function over the lifetime of the animal.
Differentiation of Clonal Complex 59 Community-Associated Methicillin-Resistant Staphylococcus aureus in Western Australia

ABSTRACT Clonal complex 59 (CC59) community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains were characterized using pulsed-field gel electrophoresis, spa typing, multilocus sequence typing, diagnostic DNA microarrays, and PCRs targeting staphylococcal cassette chromosome mec (SCCmec) elements and Panton-Valentine leukocidin (PVL). Six distinct groups within CC59 were characterized. At least seven different variants of SCCmec elements were identified (IVa [2B], IVb [2B], IVd [2B], IV variant [2B], IVa [2B&5], V variant [5C2], and V [5C2&5]). (The structural type is indicated by a Roman numeral, with a lowercase letter indicating the subtype, and the ccr complex and the mec complex are indicated by an Arabic numeral and an uppercase letter, respectively. Where there is an extra ccr element, this is indicated by “&” and an Arabic numeral designating the ccr type.) The first group is similar to the American sequence type 59 (ST59) MRSA-IV CA-MRSA strain USA1000. The second group includes a PVL-negative ST87 strain with an SCCmec element of subtype IVb (2B). The third group comprises PVL-variable ST59 MRSA-IV strains harboring multiple SCCmec IV subtypes. PVL-negative ST59 MRSA strains with multiple or composite SCCmec elements (IVa [2B&5]) form the fourth group. Group 5 corresponds to the internationally known “Taiwan clone,” a PVL-positive strain with a variant SCCmec element (V [5C2&5]). This strain proved to be the most common CC59 MRSA strain isolated in Western Australia. Finally, group 6 encompasses the ST59 MRSA-V variant (5C2). The differentiation of CC59 into groups and strains indicates a rapid evolution and spread of SCCmec elements. Observed differences between groups of strains as well as intrastrain variability within a group facilitate the tracing of their spread.
Targeting the Apoptotic Pathway with BCL-2 Inhibitors Sensitizes Primary Chronic Lymphocytic Leukemia Cells to Vesicular Stomatitis Virus-Induced Oncolysis

ABSTRACT Chronic lymphocytic leukemia (CLL) is characterized by clonal accumulation of CD5+ CD19+ B lymphocytes that are arrested in the G0/G1 phase of the cell cycle and fail to undergo apoptosis because of overexpression of the antiapoptotic B-cell CLL/lymphoma 2 (BCL-2) protein. Oncolytic viruses, such as vesicular stomatitis virus (VSV), have emerged as potential anticancer agents that selectively target and kill malignant cells via the intrinsic mitochondrial pathway. Although primary CLL cells are largely resistant to VSV oncolysis, we postulated that targeting the apoptotic pathway via inhibition of BCL-2 may sensitize CLL cells to VSV oncolysis. In the present study, we examined the capacity of EM20-25—a small-molecule antagonist of the BCL-2 protein—to overcome CLL resistance to VSV oncolysis. We demonstrate a synergistic effect of the two agents in primary ex vivo CLL cells (combination index of 0.5; P < 0.0001). In a direct comparison of peripheral blood mononuclear cells from healthy volunteers with primary CLL, the two agents combined showed a therapeutic index of 19-fold; furthermore, the combination of VSV and EM20-25 increased apoptotic cell death in Karpas-422 and Granta-519 B-lymphoma cell lines (P < 0.005) via the intrinsic mitochondrial pathway. Mechanistically, EM20-25 blocked the ability of the BCL-2 protein to dimerize with proapoptotic BAX protein, thus sensitizing CLL to VSV oncolytic stress. Together, these data indicate that the use of BCL-2 inhibitors may improve VSV oncolysis in treatment-resistant hematological malignancies, such as CLL, with characterized defects in the apoptotic response.
Predictors for morbidity and mortality following non-traumatic splenectomy at the University Hospital, Jeddah, Saudi Arabia.

OBJECTIVE To determine the pre-operative predictors of morbidity and mortality of patients undergoing elective splenectomy for non-trauma indications. METHODS Analysis of 123 patients who underwent splenectomy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 1986-1996. Data collected included patients' demographic data, indication for splenectomy, laboratory data, details of operative procedure and postoperative events for morbidity and mortality. Statistical analysis was carried out using the Chi-square test. RESULTS Of the patients, 69% were males and 31% females with ages ranging from 13-72 years (mean 39 years). Portal hypertension constituted 55% of the indications and benign hematological conditions 26%. The morbidity rate was 27.6% and the commonest complication was chest and wound infection in 6.6% and 5.7%, respectively. Age of >50 years, pre- and postoperative haematocrit of <33%, thoraco-abdominal approach and operative time of >120 min had P values of < 0.05, <0.002, <0.03 and <0.03, respectively for postsplenectomy mortality. CONCLUSIONS According to this study, age of >50 years is a significant predictor for morbidity following splenectomy, whereas age >50 years, pre- and postoperative haematocrit of <33%, thoraco-abdominal approach and operative duration >120 min were significant predictors of postsplenectomy mortality.
Disease burden of post-infectious irritable bowel syndrome in The Netherlands

SUMMARY Post-infectious irritable bowel syndrome (PI-IBS) has been established as a sequel of infectious intestinal disease (IID). The aim of this study was to estimate the burden of PI-IBS caused by the pathogens Campylobacter, Salmonella and Shigella, and to compare this with other outcomes associated with these pathogens. The attributable risk of PI-IBS due to bacterial pathogens was calculated and linked to national data on gastroenteritis incidence and measures for severity and duration of illness in order to estimate the burden of PI-IBS. One year post-infection, IBS developed in 9% of patients with bacterial IID. The burden of PI-IBS adds over 2300 disability adjusted life years to the total annual disease burden for the selected pathogens. PI-IBS is a frequent sequel of IID, resulting in a considerable disease burden compared to other outcomes. If this relationship is not considered, this will result in an underestimation of the disease burden of IID.
Switching Policies for Mold Level Control in Continuous Casting Plants

The problem of controlling the liquid level in the mold of a continuous casting process is considered. Essentially, the system operates in two different modes: (a) one in which the system is affected only by small-amplitude high-frequency disturbances, and (b) one in which the system is affected by a comparatively large disturbance related to an abrupt unclogging phenomenon. To cope with the first situation, the control system must exhibit a narrow bandwidth, whereas the second situation requires a much larger bandwidth. The two conflicting requirements lead naturally to the design of two distinct controllers and a switching rule that activates either controller according to the operating condition. Due to the time-varying nature of the resulting control system, the controllers should be properly realized to guarantee stability; to this purpose, a recent result on switching systems is invoked. Since the sudden switching between controllers can cause controller and actuator output bumps, a soft switching policy that still ensures stability is also proposed. Simulations and laboratory experiments carried out on an electronic analogue of the process show the effectiveness of the suggested control schemes.
Implementation of the World Health Organization surgical safety checklist at a university hospital in Thailand.

BACKGROUND Compliance with the World Health Organization (WHO) surgical safety checklist may reduce preventable adverse events. However, compliance may be difficult to implement in Thailand. This study was conducted to examine compliance with the WHO checklist at a Thai university hospital. METHODS A descriptive study was conducted among 4,340 patients undergoing surgery in nine departments from March to August 2009. The compliance rates were computed. RESULTS The highest compliance rate (91.4%) during the sign-in period was with patients' confirmation of their identity, operative site, procedure, and consent. However, only 19.4% of the surgical sites were marked. In the time-out period, surgical teams had introduced themselves by name and role in 79% of the operations; and in 95.7% of the cases, the patient's name, the incision site, and the procedure had been confirmed. Antibiotic prophylaxis had been given within 60 min before the incision in 71% of the cases. For 83% of the operations, the surgeons reviewed crucial events whereas only 78.4% were reviewed by the anesthetists. Sterility had been confirmed by the operating room nurses for every patient, but the essential imaging was displayed at a rate of only 64.4%. In the sign-out period, nurses correctly confirmed the name of the procedure orally in 99.5% of the cases. Instrument, sponge, and needle counts were completed and the specimen was labeled in most cases, 96.8% and 97.6%, respectively. Equipment-related problems were identified in 4.4% of the cases, and 100% of them were addressed. The surgeon, anesthetist, and nurse reviewed the key concerns for recovery and management of the patient at the rate of 85.1%. CONCLUSIONS The WHO checklist can be implemented in a developing country. However, compliance with some items was extremely low, reflecting different work patterns and cultural norms. Additional education and enforcement of checklist use is needed to improve compliance.
Myocardial Infarction in Coronary Bypass Surgery Using On‐Pump, Beating Heart Technique with Pressure‐and Volume‐Controlled Coronary Perfusion

Abstract Background: Even with the current aerobic techniques in myocardial protection, perioperative myocardial infarction can still occur. In this study, we sought to find out whether there is a method‐specific mechanism of ischemic injury in coronary bypass surgery using an on‐pump beating heart technique. For this reason, we investigated localization and the extent of myocardial infarction in correlation to the severity of coronary artery stenosis. We discuss strategies for reduction of infarction incidence. Methods: 34 patients, who after isolated coronary bypass procedure developed non‐Q or Q wave infarction were selected for the study. In 12 of 34 patients (group A) beating heart technique and in 22 of 34 patients (group B) cardioplegic arrest was used for myocardial protection. The study was conducted retrospectively and included patients with stable, unstable, and postinfarction angina without preoperative enzymatic evidence of ischemic injury and with technically noncomplicated coronary bypass grafting. Excluded from the study were emergency and redo procedures. In group A, in all instances, the left anterior descending artery was grafted as the last vessel and while distal anastomoses were constructed, coronary perfusion was maintained by using a perfusion catheter. Results: Most patients in both groups had triple‐vessel disease (10 of 12 patients group A; 17 of 22 patients group B), all patients received complete revascularization; 7 of 12 patients in group A and 5 of 22 patients in group B had significant or critical left main stem stenosis. In group A, 11 infarctions occurred in LAD‐(12 stenotic), 1 in CX(11 stenotic), and 1 in RCA‐(11 stenotic) supply area, four were Q wave infarctions. In group B, eight infarctions occurred in LAD (22 stenotic), four in CX (17 stenotic), and 14 in RCA (20 stenotic) supply area, eight were Q wave infarctions. In group A, the infarction incidence in the LAD area was 10‐times higher than in CX and RCA areas. In group B, the infarction incidence in the RCA area was 2‐and 3‐times higher than in the LAD and CX areas, respectively. In both groups no correlation between infarction incidence and severity of stenosis was observed. Conclusions: Using an on‐pump beating heart technique, higher coronary perfusion pressures, avoidance of extreme upward retraction of the heart during revascularization of the CX‐branch, as well as choosing the revascularization of the LAD as the first vessel, could possibly contribute to better myocardial protection. In hearts arrested with cardioplegic solution, the right ventricle is probably more susceptible to ischemic injury, especially when RCA is poorly collateralized. For adequate protection, choosing the revascularization of the RCA as the first vessel with immediate repeated cardioplegia via a RCA graft, higher perfusion pressures and antegrade with retrograde cardioplegia delivery, may be advantageous.
The role of nursing education after a cardiac event

Background: After a major cardiovascular event, patients experience many problems regarding the outcome of the disease or rehabilitation including concern about return in their previous life. Recovering from a cardiac event is a complex procedure that presents psychological and physical needs that continue after discharge from hospital. The purpose of this review was to explore the role of nursing education after a cardiac event or procedure. Material and Methods: Studies published in English between 2002 and 2011 were selected through a computer-assisted literature search (i.e., Pubmed http://igm.nlm.nih.gov, and Scopus www.scopus.com). The computer searches used combinations of key words relating to the role of nursing (i.e., nursing support, nursing training, nursing education, coronary artery disease) and cardiac rehabilitation. Results: Many studies have highlighted the value of nursing support in cardiac rehabilitation programs. In particular, there is an amount of evidence that a nurse- led educational program is closely associated with reduce rate of complications, of anxiety following cardiac events and readmissions to hospital. Moreover, the therapeutic lifestyle-change intervention into a nursing program effectively modifies cardiac risk factors and may improve prognosis. Conclusion: The benefits of nursing support in cardiac rehabilitation patients can improve health outcomes and reduce the risk of a new cardiac event. It is of most importance for nurses to meet the rehabilitative care needs of patients through education, support, supervision and reinforcement.