Miracle-dz/UniFAR-FTUs huggingface dataset:
A translocation between Xq21.33 and 22q13.33 causes an intragenic SHANK3 deletion in a woman with Phelan–McDermid syndrome and hypergonadotropic hypogonadism

Chromosome 22q13 monosomy has been described as a contiguous gene syndrome. Localized in the critical region, SHANK3 is likely to play a key role in the expression of the clinical phenotype. SHANK3 mutations have also been reported in autistic patients without a syndromic phenotype. We report on a 20‐year‐old woman with mental retardation carrying a de novo translocation between chromosome Xq21.33 and 22q13.33, associated with a duplication on Xq21.33 and deletion on 22q13.33. As a child her development was characterized by disturbed social interaction, stereotypic hand movements and ritualistic behavior and she was considered at one time to have autistic features. All these traits match the 22q13 deletion syndrome (Phelan–McDermid syndrome, OMIM 606232), likely due to the deletion overlapping the last two exons of the SHANK3 gene. Our patient harbors the smallest and most distal SHANK3 deletion described to date, yet resulting in the full spectrum of the Phelan–McDermid syndrome. In addition, she has hypergonadotropic hypogonadism with low estrogen level, high FSH level, and irregular menstruation. Intriguingly, chromosome translocations affecting the chromosome band Xq21 can result in premature ovarian failure. © 2011 Wiley‐Liss, Inc.
New Mode of Action for a Knottin Protein Bioinsecticide

PA1b (for pea albumin 1 subunit b) is a plant bioinsecticide lethal to several pests that are important in agriculture or human health. PA1b belongs to the inhibitory cystine knot family or knottin family. Originating from a plant (the garden pea) commonly eaten by humans without any known toxic or allergic effects, PA1b is a candidate for transgenic applications and is one of the most promising biopesticides for pest control. Using whole-cell patch-clamp techniques on Sf9 PA1b-sensitive lepidopteran insect cells, we discovered that PA1b reversibly blocked ramp membrane currents in a dose-dependent manner (EC50 = 0.52 μm). PA1b had the same effect as bafilomycin, a specific inhibitor of the vacuolar proton pump (V-type H+-ATPase), and the PA1b-sensitive current depended on the internal proton concentration. Biochemical assays on purified V-ATPase from the lepidopteran model Manduca sexta showed that PA1b inhibited the V1V0-type H+-ATPase holoenzyme activity (IC50 ∼ 70 nm) by interacting with the membrane-bound V0 part of the V-ATPase. V-ATPase is a complex protein that has been studied increasingly because of its numerous physiological roles. In the midgut of insects, V-ATPase activity is essential for energizing nutrient absorption, and the results reported in this work explain the entomotoxic properties of PA1b. Targeting V-ATPase is a promising means of combating insect pests, and PA1b represents the first peptidic V-ATPase inhibitor. The search for V-ATPase inhibitors is currently of great importance because it has been demonstrated that V-ATPase plays a role in so many physiological processes.
Management of Acute and Subacute Puerperal Uterine Inversion with Intravenous Nitroglycerin

Abstract Background: Uterine inversion is an unpredictable entity, with more than one-half of cases reported without detectible precipitants. Hemorrhage can be rapid and life-threatening, requiring prompt recognition and aggressive management. Cases: Case 1: A 25-year-old female, para 1, with complete uterine inversion presented as a case of postpartum hemorrhage and this was managed successfully with intravenous (IV) nitroglycerine. Case 2: A second case involved partial uterine inversion, in a 22-year-old female, para 1, who had a retained placenta. The inversion was not corrected by anesthesia but was corrected by IV nitroglycerine without any side-effects. Results: Both cases were treated successfully with the use of IV nitroglycerin. Both women had postpartum hemorrhage caused by uterine inversion. IV nitroglycerin was found to be effective and was not associated any adverse effects. Conclusions: General anesthetics are generally used for uterine relaxation in cases of uterine inversion but these age.
The “eye of the tiger” sign

An 8-year-old boy presented with recurrent falls while walking and abnormal twisting postures of all four limbs for last 2 yr. He also had cognitive decline and decrease in speech output. His elder brother died of similar illness at the age of 11 yr. Examination revealed generalized dystonia, spasticity and dysarthria. Fundus examination showed bilateral retinal pigmentary changes and optic atrophy (Fig. 1). Magnetic resonance imaging of brain revealed hypo-intense globus pallidi with central hyperintensity, i.e. “eye of the tiger” sign on T2-weighted images (Fig. 2). These findings were consistent with the diagnosis of pantothenate kinase associated neurodegeneration (PKAN). Genetic testing could not be performed because of financial constraints. PKAN, formerly called Hallervorden-Spatz disease is a form of neurodegenerationwith brain iron accumulation, inherited in an autosomal recessive manner [1]. PKAN is characterized by progressive dystonia, rigidity, dysarthria, intellectual deterioration and pigmentary retinopathy starts before 10 yr of age. The “eye of the tiger” sign describes the central region of hyperintensity surrounded by a rim of hypointensity on coronal or transverse T2-weighted images of the globus pallidus. The hypointensity on T2-weighted image is because of
Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene

The association of progeroid features and lipodystrophy was very recently described in a female adult with additional manifestations of Marfan syndrome. Mutation analysis of the fibrillin I (FBN1) gene revealed a novel heterozygous frameshift mutation at the 3′ end in that patient. Here, we report on a 3.5‐year‐old girl with progeroid facial signs of neonatal onset, lipodystrophy, large head circumference with corresponding hydrocephaly, and tall stature at the end of infancy. Her facial appearance showed convincing clinical similarities to the above‐mentioned case. We identified a novel heterozygous de novo splice site mutation c.8226+1G>T affecting the last intron of FBN1. We suggest a specific clinical entity characterized by progeroid facial features, lipodystrophy, and at least some clinical signs of Marfan syndrome is associated with a subset of mutations located at the 3′ end of FBN1. This phenotype which is different from that of classical Marfan syndrome could be caused by a truncated FBN1 protein which could escape nonsense‐mediated RNA decay. © 2011 Wiley‐Liss, Inc.
Neuronostatin, a Novel Peptide Encoded by Somatostatin Gene, Regulates Cardiac Contractile Function and Cardiomyocyte Survival*

Background: Neuronostatin peptide is a somatostatin gene derivative, whose functions are largely unknown. Results: Neuronostatin activates p38 MAPK and JNK attenuating endothelin-1-induced cardiac contractility and compromising cardiomyocyte viability. Conclusion: Neuronostatin has multiple biological effects in cardiomyocytes. Significance: Receptors for neuronostatin need to be identified to further characterize the functions of the peptide. Neuronostatin, a recently discovered peptide encoded by somatostatin gene, is involved in regulation of neuronal function, blood pressure, food intake, and drinking behavior. However, the biological effects of neuronostatin on cardiac myocytes are not known, and the intracellular signaling mechanisms induced by neuronostatin remain unidentified. We analyzed the effect of neuronostatin in isolated perfused rat hearts and in cultured primary cardiomyocytes. Neuronostatin infusion alone had no effect on left ventricular (LV) contractile function or on isoprenaline- or preload-induced increase in cardiac contractility. However, infusion of neuronostatin significantly decreased the positive inotropic response to endothelin-1 (ET-1). This was associated with an increase in phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK). Treatment of both neonatal and adult cardiomyocytes with neuronostatin resulted in reduced cardiomyocyte viability. Inhibition of JNK further increased the neuronostatin-induced cell death. We conclude that neuronostatin regulates cardiac contractile function and cardiomyocyte survival. Receptors for neuronostatin need to be identified to further characterize the biological functions of the peptide.
Knowing in nursing: a concept analysis.

AIM This paper is a report of an analysis of the evolution of the concept of knowing in nursing. BACKGROUND Following the seminal contribution of Carper in 1978, knowing has been discussed with increasing frequency in the nursing literature with reference to the development of nursing knowledge. Various patterns of knowing, as well as research focused on reflection on experience, have been the foundation for activities and research designed to improve practice as well as patient care in clinical, community, education, cultural and administrative settings. METHODS Rodgers' evolutionary method of concept analysis provided the framework for this analysis. The data source was a search of literature published from 1978 to 2007. Three aims guided the analysis: to understand how the concept of knowing is used in nursing, how it is used in other health-related disciplines and how the concept has evolved into the current interpretation. DISCUSSION Analysis revealed that knowing in nursing refers to a uniquely personal type of knowledge constructed of objective knowledge interfaced with the individual's subjective perspective on personal experience. Knowing is a dynamic process and a result of personal reflection and transformation as the individual lives and interacts in the world. Its antecedents are experience, awareness and reflection. The consequences are understanding, finding meaning and transformation. CONCLUSION This analysis illuminates an area in which nursing has carved out its own niche in healthcare research. The concept of knowing in nursing practice and research reflects a focus on the individual experience of health and illness.
Emotional stability of nurses: impact on patient safety.

AIM This paper is a report of a study conducted to examine the influence of the emotional stability of nurses on patient safety. BACKGROUND Individuals with greater emotional stability are less likely to exhibit strong emotional reactions to stressful situations, and tend to be more proactive and successful in problem-solving. Effectively managing patient safety is a priority concern in countries where nurses face high pressure. A heavy work load leads to burnout (a syndrome associated with negative emotions), reduced job satisfaction and increased turnover. While emotional stability influences job performance in various contexts, its influence on patient safety has not been addressed. METHOD A cross-sectional design was adopted. The sample comprised 263 nurses working in two Taiwanese medical centres. The data were collected in 2007-2008, with a response rate of 926%. All participants were nursing college graduates aged below 50 years. Participants provided information on both their emotional stability and patient safety. Staffing adequacy, hospital, and years of nursing experience served as control variables. FINDINGS Hierarchical regression analysis indicated that emotional stability predicted patient safety (beta = 0.18, P < 001). The addition of emotional stability as a predictor of patient safety increased the associated explained variance (deltaR2 = 0.03, P < 0.01). CONCLUSION It is important for to managers create an organisational climate that promotes the emotional stability of nurses. This could help to improve global patient safety by reducing the frequency of adverse events.
Vasoactive Intestinal Peptide-mediated Gene Therapy for Diabetes

All patients with type 1 diabetes (T1DM) and most patients with type 2 diabetes (T2DM) become insulin dependent due to the progressive nature of the disease, eventually leading to beta-cell loss. The increase in apoptosis, but not the decrease in new islet formation or beta-cell replication, is blamed for the loss of beta-cell mass observed in patients with T2DM. Thus, therapeutic approaches that either interfere with apoptosis of beta cells and/or increase beta-cell mass have the potential not only for managing hyperglycemia but also for reversing disease progression. Vasoactive intestinal peptide (VIP) is a neuropeptide of the secretin family just like GLP1 and PACAP with equipotent insulinotropic effects. More importantly, it is an effective anti-inflammatory agent involved in suppression of Th1 immune response and activation of regulatory T cells for inducing immune tolerance. For this reason, VIP is now considered to be an emerging therapeutic agent for autoimmune diseases such as rheumatoid arthritis, ulcerative colitis, multiple sclerosis, and T1DM. Despite all these advantages, VIP is extremely sensitive to peptidases (DPP-4) present in most tissues. Thus, multiple injections of VIP at high doses are required to observe any therapeutic effect. Contrary to using peptide forms of therapeutic agents, some gene therapy vectors can provide long-term and stable gene expression. Thus, viral and non-viral VIP gene delivery methods have been under development. Despite the successful results obtained from these studies, especially against autoimmune diseases, some limitations of using gene therapy vectors were revealed in recent studies. For example, the clinical efficacy of plasmid DNA transfer is low. Adenoviral vectors only provide transient gene expression due to the antigenic character of adenoviral epitopes. AAV has limited cargo capacity and low transduction efficiency. Compared with other gene therapy vectors, lentiviral vectors appear to be the vector of choice when considering long-term gene expression, transduction efficacy, and safety. Consequently, the testing of the efficacy of lentivirus-mediated VIP gene delivery against diabetes became an essential issue to discuss in experimental animal model of diabetes.
Structural Insights into Charge Pair Interactions in Triple Helical Collagen-like Proteins*

Background: Charged residues, abundant in collagen, participate in stabilizing and packing interactions. Results: Two contact geometries, axial and lateral, are observed in charge pair hydrogen bonding. Conclusion: Axial salt bridges provide greater stabilization to the triple helical fold than lateral ones. Significance: Understanding interstrand amino acid interactions in collagen will improve interpretation of natural collagen and will allow more effective design of collagen mimics. The collagen triple helix is the most abundant protein fold in humans. Despite its deceptively simple structure, very little is understood about its folding and fibrillization energy landscape. In this work, using a combination of x-ray crystallography and nuclear magnetic resonance spectroscopy, we carry out a detailed study of stabilizing pair-wise interactions between the positively charged lysine and the negatively charged amino acids aspartate and glutamate. We find important differences in the side chain conformation of amino acids in the crystalline and solution state. Structures from x-ray crystallography may have similarities to the densely packed triple helices of collagen fibers whereas solution NMR structures reveal the simpler interactions of isolated triple helices. In solution, two distinct types of contacts are observed: axial and lateral. Such register-specific interactions are crucial for the understanding of the registration process of collagens and the overall stability of proteins in this family. However, in the crystalline state, there is a significant rearrangement of the side chain conformation allowing for packing interactions between adjacent helices, which suggests that charged amino acids may play a dual role in collagen stabilization and folding, first at the level of triple helical assembly and second during fibril formation.
Induction of DNA Damage Signaling upon Rift Valley Fever Virus Infection Results in Cell Cycle Arrest and Increased Viral Replication*

Background: RVFV is a cytoplasmic replicating RNA virus that infects both humans and livestock. Results: DNA damage signaling and cell cycle arrest are induced following RVFV infection. Conclusion: The ATM signaling pathway and cell cycle arrest are important for RVFV replication. Significance: Studying virally induced signaling pathways is important for host-based therapeutic design and understanding host-pathogen interactions. Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus infecting a wide range of vertebrate hosts. Of particular interest is the nonstructural NSs protein, which forms large filamentous fibril bundles in the nucleus. Past studies have shown NSs to be a multifaceted protein important for virulence through modulation of the interferon response as well acting as a general inhibitor of transcription. Here we investigated the regulation of the DNA damage signaling cascades by RVFV infection and found virally inducted phosphorylation of the classical DNA damage signaling proteins, ataxia-telangiectasia mutated (ATM) (Ser-1981), Chk.2 (Thr-68), H2A.X (Ser-139), and p53 (Ser-15). In contrast, ataxia-telangiectasia mutated and Rad3-related kinase (ATR) (Ser-428) phosphorylation was decreased following RVFV infection. Importantly, both the attenuated vaccine strain MP12 and the fully virulent strain ZH548 showed strong parallels in their up-regulation of the ATM arm of the DNA damage response and in the down-regulation of the ATR pathway. The increase in DNA damage signaling proteins did not result from gross DNA damage as no increase in DNA damage was observed following infection. Rather the DNA damage signaling was found to be dependent on the viral protein NSs, as an NSs mutant virus was not found to induce the equivalent signaling pathways. RVFV MP12-infected cells also displayed an S phase arrest that was found to be dependent on NSs expression. Use of ATM and Chk.2 inhibitors resulted in a marked decrease in S phase arrest as well as viral production. These results indicate that RVFV NSs induces DNA damage signaling pathways that are beneficial for viral replication.
What does quality care mean to nurses in rural hospitals?

AIM This paper is a report of a study conducted to answer the question: 'How do rural nurses and their chief nursing officers define quality care? ' BACKGROUND Established indicators of quality care were developed primarily in urban hospitals. Rural hospitals and their environments differ from urban settings, suggesting that there might be differences in how quality care is defined. This has measurement implications. METHODS Focus groups with staff nurses and interviews with chief nursing officers were conducted in 2006 at four rural hospitals in the South-Eastern United States of America. Data were analysed using conventional content analysis. FINDINGS The staff nurse and chief nursing officer data were analysed separately and then compared, exposing two major themes: 'Patients are what matter most' and 'Community connectedness is both a help and a hindrance'. Along with conveying that patients were the utmost priority and all care was patient-focused, the first theme included established indicators of quality such as falls, pressure ulcers, infection rates, readmission rates, and lengths of stay. A new discovery in this theme was a need for an indicator relevant for rural settings: transfer time to larger hospitals. The second theme, Community Connectedness, is unique to rural settings, exemplifying the rural culture. The community and hospital converge into a family of sorts, creating expectations for quality care by both patients and staff that are not typically found in urban settings and larger hospitals. CONCLUSION Established quality indicators are appropriate for rural hospitals, but additional indicators need to be developed. These must include transfer times to larger facilities and the culture of the community.
Effectiveness of cutaneous warming systems on temperature control: meta-analysis.

AIM This paper is a report of a meta-analysis to identify the effectiveness of different types of cutaneous warming systems in temperature control for patients undergoing elective surgery. BACKGROUND Hypothermia is a common and serious complication of surgery. Different cutaneous warming systems are used to prevent hypothermia during surgery but there have been no previous meta-analyses of the effectiveness of different warming systems in controlling temperature. DATA SOURCES We conducted a search of the CINAHL (2000 to April 2009), Medline (2000 to April 2009), Embase (2000 to April 2009) and the Cochrane Register of Controlled Trials (2000 to April 2009) databases for randomized controlled trials published in English, Spanish and Portuguese. The primary outcome measure of interest was core body temperature. METHODS A systematic review incorporating meta-analysis was carried out. RESULTS From 329 papers, 23 trials compared warming systems. Forced-air warming systems had a strong tendency towards superior temperature control over passive insulation via cotton blankets (mean difference: 0.29 degrees C; 95% confidence interval: -0.02 to 0.59, three trials 292 patients) and radiant warming systems (mean difference: 0.16 degrees C; 95% confidence interval: -0.01 to 0.33, three trials, 161 patients). However, circulating water garments tended to be more effective than forced-air warming systems (mean difference: -0.73 degrees C; 95% confidence interval: -1.51 to 0.05, I(2) = 97%; four trials, 198 patients). Pooled results approached statistical significance and indicated clinically meaningful differences in temperature control. CONCLUSION Current evidence suggests that circulating water garments offer better temperature control than forced-air warming systems, and both are more effective than passive warming devices.
Framework for the detection and classification of colorectal polyps

In this thesis we propose a framework for the detection and classi cation of colorectal polyps to assist endoscopists in bowel cancer screening. Such a system will help reduce not only the miss rate of possibly malignant polyps during screening but also reduce the number of unnecessary polypectomies where the histopathologic analysis could be spared. Our polyp detection scheme is based on a cascade lter to pre-process the incoming video frames, select a group of candidate polyp regions and then proceed to algorithmically isolate the most probable polyps based on their geometry. We also tested this system on a number of endoscopic and capsule endoscopy videos collected with the help of our clinical collaborators. Furthermore, we developed and tested a classi cation system for distinguishing cancerous colorectal polyps from non-cancerous ones. By analyzing the surface vasculature of high magni cation polyp images from two endoscopic platforms we extracted a number of features based primarily on the vessel contrast, orientation and colour. The feature space was then ltered as to leave only the most relevant subset and this was subsequently used to train our classi er. In addition, we examined the scenario of splitting up the polyp surface into patches and including only the most feature rich areas into our classi er instead of the surface as a whole. The stability of our feature space relative to patch size was also examined to ensure reliable and robust classi cation. In addition, we devised a scale selection strategy to minimize the e ect of inconsistencies in magni cation and geometric polyp size between samples. Lastly, several techniques were also employed to ensure that our results will generalise well in real world practise. We believe this to be a solid step in forming a toolbox designed to aid endoscopists not only in the detection but also in the optical biopsy of colorectal polyps during in vivo colonoscopy.