Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain mineralocorticoid receptors: orchestrators of hypertension and end-organ disease

Purpose of review‘New’ tasks have been discovered for aldosterone and its receptor, the mineralocorticoid receptor, within both epithelial tissues of vectorial ion and water transport, such as the kidney, and non-epithelial organs, including the brain, heart and vessels. Promising results of clinical trials using low doses of mineralocorticoid receptor antagonists to forestall end-organ disease is resulting in an increase in their use, yet the biology of the mineralocorticoid receptor is far from clear. Recent findingsMineralocorticoid receptors within the kidney, heart and blood vessels mediate direct effects of aldosterone, including tissue inflammation, hypertrophy and fibrosis, that are independent of blood pressure. Activation, by aldosterone, of mineralocorticoid receptors in the brain increases central sympathetic nervous system drive to the periphery, thereby producing hypertension through multiple mechanisms, and increases levels of proinflammatory cytokines in both the circulation and peripheral tissues. Blocking of the mineralocorticoid receptor of the forebrain lowers the levels of peripheral tissue cytokines, including those induced by ischemic injury in the heart. Aldosterone is produced within the heart, blood vessels and brain, potentially liberating regulation of local concentrations of the steroid from peripheral mechanisms of control. A conundrum yet to be explained is the ligand-dependent functional specificity of the mineralocorticoid receptor in some non-epithelial tissues, which may be crucial to our understanding the end-organ pathophysiology of hypertension. SummaryNew technology is rapidly adding layers of complexity to, rather than simplifying, our understanding of the facile terms ‘hemodynamic homeostasis’ and ‘end-organ’ disease, but within this new knowledge lies the promise of better, more precise treatment of hypertension and its sequelae.
Mannose-binding Lectin Genotype Influences Frequency and Duration of Infectious Complications in Children With Malignancy

Children with cancer receiving identical treatment differ in their experience of infection, suggesting that variations in immunity may influence susceptibility to infection. Studies of the influence of mannose-binding lectin (MBL), an important component of the innate immune system, in children with febrile neutropenia (FN) have yielded conflicting results. We examined the role of MBL in infection susceptibility in the largest cohort of children with cancer reported to date. MBL levels were measured and genotyping performed on children (⩽16 y) receiving chemotherapy for cancer in London, UK. Clinical data from FN episodes were recorded prospectively. MBL status was assessed in 269 children; 513 episodes of FN were captured from 211 patients. Patients with MBL2 polymorphisms experienced more FN episodes than wildtype genotype (median 2 vs. 1, respectively; P=0.074) and more episodes with documented infection (P=0.045). Patients experiencing multiple FN episodes had lower MBL levels (P=0.036). MBL genotype influenced duration of episode in some groups: high-risk MBL-deficient patients spent up to 5 nights longer/episode in hospital than equivalent wildtypes. These results indicate that MBL deficiency influences both susceptibility to and outcome of FN episodes and may be most important in those patients at higher risk of complications of FN.
The clown doctors.

BACKGROUND In 1996 The Humour Foundation was established in Australia, drawing on inspiration from the work of Patch Adams and the Clown Care Unit in New York. The mission statement of the Foundation is to introduce and promote the health benefits of humour to patients, their families and health care professionals. OBJECTIVE To describe the work of the Clown Doctors in Australia and the role of humour in relieving suffering. DISCUSSION Clown Doctor Units have been established at several major hospitals throughout Australia. They use performance skills, humour, empathy and sensitivity to support, nourish, divert and help patients (and staff) cope with difficult situations.
Incidence and physical properties of PSE chicken meat in a commercial processing plant

It is known that PSE meat present important functional defects, such as low water holding capacity and ultimate pH, which may compromise the quality of further-processed meat products. In this study, L* (lightness), a* (redness), and b* (yellowness) values of 500 chicken breast fillets were determined using a portable colorimeter (Minolta, model CR-400) in a commercial processing plant. Fillets were considered pale when their L* was ≥49. Out of those samples, 30 fillets with normal color and 30 pale fillets were evaluated as to pH, drip loss, cooking loss, water holding capacity, shear force, and submitted to sensorial analysis. An incidence of 10.20% PSE meat was determined. Pale and normal fillets presented significantly different (p≤0.05) pH values, L* and a* values, water holding capacity, drip loss, and cooking loss, demonstrating changes in the physical properties of PSE meat. Shear force and sensorial characteristics were not different (p>0.05) between pale and normal fillets. Despite the significant differences in meat physical properties, these were not perceived by consumers in terms of tenderness, aspect, and flavor. The observed incidence of PSE may cause losses due to its low water retention capacity.
The impact of components of fine particulate matter on cardiovascular mortality in susceptible subpopulations

Background: Several studies have demonstrated associations between daily mortality and ambient particulate matter less than 2.5 microns in diameter (fine particles or PM2.5). Few, however, have examined the relative toxicities of PM2.5 constituents, including elemental carbon and organic carbon (EC and OC, respectively), nitrates and transition metals. There is also little information about whether associations between PM2.5 constituents and mortality are modified by socioeconomic and demographic factors. Aim: To examine associations of daily cardiovascular mortality with PM2.5 and its constituents after stratification by gender, race/ethnicity and education, using data from six California counties during 2000 to 2003. Methods: The association of daily counts of cardiovascular mortality with PM2.5 components was analysed using time-series regression analyses. Poisson models with natural splines were used to control for time-varying covariates such as season and weather. Separate models were run after stratification by gender, race/ethnicity (White, Hispanic, Black) and education (high school graduation or not). Models were run for each county and results were combined using random effects meta-analysis. Results: Daily counts of cardiovascular mortality were associated with PM2.5 and several of its species including EC, OC, nitrates, sulphates, potassium, copper and iron. For many of these species, there were significantly higher effect estimates among those with lower educational attainment and Hispanic individuals. For example, while essentially no association was observed for individuals who graduated from high school, an interquartile change in several of the components of PM2.5 was associated with a 3–5% increase in daily mortality among non-high school graduates. Conclusion: There is evidence that several PM2.5 constituents may represent important contributors to cardiovascular mortality. Many of these constituents are generated by motor vehicles, especially those with diesel engines, and by residential wood combustion. In addition, factors associated with low educational attainment may increase susceptibility to PM2.5 and its components.
The Hereditary Factor in Arterial Blood-pressure

The current conflict of views about the nature of essential hypertension reflects our ignorance of arterial pressure in the general population. Though reliable apparatus for the indirect measurement of bloodpressure has been available for over half a century we still do not know how arterial pressure increases with age in the population at large; we know little of the influence of environmental factors and there is disagreement about the mode of inheritance of hypertension. Investigations of these questions cannot easily be initiated from hospital practice, and it seems highly probable that the long-term study of representative populations by the modern techniques of epidemiology will contribute much to the understanding of the factors affecting blood-pressure within the next decade. Two such long-term epidemiological studies are in progress in South Wales, and this report summarizes the analyses of the genetic data derived from them. Other papers will deal with the influence of environmental and personal factors. The results reported here include data derived from the original " cross-sectional " surveys, and from the follow-up surveys which were undertaken four years later. Some of these data have been published previously (Miall and Oldham, 1955, 1957, 1958; Miall, 1962), but
Perceived successes and challenges of clinical pharmacist practitioners in North Carolina.

OBJECTIVES To describe the successes and challenges reported by current (active) and formerly practicing (inactive) CPPs and to determine the reasons why inactive CPPs discontinued advanced practice. METHODS A sampling frame, consisting of all active and inactive CPPs, was obtained from the North Carolina Boards of Medicine and Pharmacy. An electronic survey was sent to 84 active and 32 inactive CPPs. Respondents were queried regarding qualifications, experience, and practice characteristics, perceived successes, and perceived challenges. RESULTS 54 active and 22 inactive CPPs responded. Among active CPPs, 28 (51.9%) reported improved patient care outcomes and 27 (50.0%) reported an expanded scope of practice. Regarding challenges, 30 (55.6%) identified billing for services and 19 (35.2%) noted reimbursement through third parties. Among inactive CPPs, 14 (63.6%) experienced improved patient care outcomes and 11 (50.0%) said their licensure created a practice model for learners. Billing (54.5%) and reimbursement (31.8%) were the top challenges experienced by inactive CPPs. A total of 12 inactive CPPs (54.5%) discontinued CPP licensure because it was not a requirement of their current position. Three (13.6%) discontinued because of insurmountable challenges that made it difficult to continue practice. CONCLUSION Although CPPs held a perception of improved patient care outcomes, billing for services and obtaining reimbursement were reported as the most prevalent challenges and may have played a major role in CPPs becoming inactive.
Impact of Directional Antenna of Primary System Receiver in Spectrum Sensing: A Case Study

In cognitive radios, a directional antenna can be used at the primary system receiver in order to improve reception performance. The problem is that the cognitive radio sensors may not detect weak signals from the primary system transmitter far away, whereas these signals can be received by a high-sensitivity primary system receiver. The present paper describes the experimental results obtained in field trials performed in order to demonstrate the impact of various parameters (e.g., directional gain, reflections, and diffractions) in spectrum sensing.
Limitations on maximal tracking accuracy

This paper studies optimal tracking performance issues pertaining to finite-dimensional, linear, time-invariant feedback control systems. The problem under consideration amounts to determining the minimal tracking error between the output and reference signals of a feedback system, attainable by all possible stabilizing compensators. An integral square error criterion is used as a measure for the tracking error, and explicit expressions are derived for this minimal tracking error with respect to step reference signals. It is shown that plant nonminimum phase zeros have a negative effect on a feedback system's ability to reduce the tracking error, and that in a multivariable system this effect results in a way depending on not only the zero locations, but also the zero directions. It is also shown that if unity feedback structure is used for tracking purposes, plant nonminimum phase zeros and unstable poles can together play a particularly detrimental role in the achievable tracking performance, especially when the zeros and poles are nearby and their directions are closely aligned. On the other hand, if a two parameter controller structure is used, the achievable tracking performance depends only on the plant nonminimum phase zeros.
HER2 somatic mutations are associated with poor survival in HER2‐negative breast cancers

It is well documented that human epidermal growth factor receptor 2 (HER2) overexpression/amplification is associated with poor survival in breast cancer patients. However, it is largely unknown whether HER2 somatic mutations are associated with survival in HER2‐negative breast cancer patients. Here, we identified HER2 somatic mutations in tumors from 1348 unselected breast cancer patients by sequencing the entire HER2 coding region. All of these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between HER2 somatic mutations and recurrence‐free survival and distant recurrence‐free survival in this cohort of patients. We found that 27 of 1348 (2.0%) of these patients carried a HER2 somatic mutation. In vitro experiments indicated that some of the novel mutations and those with unknown functions increased HER2 activity. HER2 status was available for 1306 patients, and the HER2 somatic mutation rates in HER2‐positive (n = 353) and HER2‐negative breast cancers (n = 953) were 1.4% and 2.3%, respectively. Among the HER2‐negative patients, those with a HER2 somatic mutation had a significantly worse recurrence‐free survival (unadjusted hazard ratio = 2.67; 95% confidence interval, 1.25–5.72, P = 0.002) and distant recurrence‐free survival (unadjusted hazard ratio = 2.50; 95% confidence interval, 1.10–5.68, P = 0.004) than those with wild‐type HER2. Taken together, our findings suggested that HER2 somatic mutations occur at a higher frequency in HER2‐negative breast cancer, and HER2‐negative breast cancer patients with these mutations have poor survival. Therefore, HER2‐negative patients with a HER2 somatic mutation are potentially good candidates for HER2‐targeted therapy.
Neuroanatomical dichotomy of sexual behaviors in rodents: a special emphasis on brain serotonin

Much of the social behavior in which rodents engage is related to reproduction, such as maintaining a breeding territory, seeking mates, mating, and caring for their young. Rodents belong to the internally fertilizing species that require sexual behavior for reproduction. The dyadic, heterosexual patterns of most mammalian species are sexually dimorphic, but they also share mutual components in both sexes: sexual attraction is reciprocal, sexual initiative is assumed, appetitive behavior is engaged in, and mating involves consummatory and postconsummatory phases in females as well as in males. Serotonin, a phylogenetically ancient molecule, is the most widely distributed neurotransmitter in the brain and its signaling pathways are essential for numerous functions including sexual behavior. Since the late 1960s, brain serotonergic neurotransmission has been considered to exert an inhibitory influence on the neural mechanisms mediating sexual behavior. This contention was based mainly on the observations that a decrease in central serotonergic activity facilitated the elicitation of sexual behavior, whereas an increase in central serotonergic activity attenuated it. However, the discovery of over 14 types of serotonin receptors has added numerous layers of complexity to the study of serotonin and sexual behavior. Evidence shows that, upon activation, certain receptor subtypes facilitate, whereas some others suppress, sexual behavior, as well as sexual arousal and motivation. Furthermore, the role of these receptors has been shown to be different in the male and female sexes. The use of serotonergic pharmacological interventions, mouse strains with genetic polymorphisms causing alterations in the levels of brain serotonin, and animal models with genetic manipulations of various serotonin effectors has helped delineate the fundamental role of this neurotransmitter in the regulation of sexual behavior. This review aims to examine the basics of the components of female and male sexual behavior and the participation of the serotonin system in the modulation of these behaviors, with emphasis on rodents.
Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura

We prospectively investigated the prevalence of Helicobacter pylori (H. pylori) infection in a cohort of 54 adult Serbian patients with chronic idiopathic thrombocytopenic purpura (ITP), and examined the effects of its eradication on their platelet counts. H. pylori infection was diagnosed in 39/54 (72.2%) patients, using the 14C-urea breath test; and was significantly higher than in the healthy Serbian population (55% P < 0.05). H. pylori-positive patients were significantly older than H. pylori-negative patients (P = 0.006), though there were no significant differences regarding gender, disease duration, mean platelet counts, previous therapies and spleen status between H. pylori-positive and H. pylori-negative patients. Successful eradication was confirmed in 23/30 (77%) treated patients. Stable platelet recovery was registered in 6/23 eradicated patients (26.1%) and maintained for 18 months. Complete and partial remissions were achieved in two and four patients, respectively, including one highly refractory patient. A significant mean platelet recovery was seen 6 months after successful H. pylori eradication in the group of 23 patients (P < 0.05). No platelet recovery was registered in either H. pylori-negative (n = 15), untreated H. pylori-positive patients (n = 9) or H. pylori-positive non-eradicated patients (n = 7). Even though the pathogenetic mechanisms of H. pylori-induced thrombocytopenia remain obscure, the results of this small prospective study support the use of H. pylori eradication as an effective non-immunosuppressive treatment for chronic ITP.
On the Non-Robustness of Memoryless Path-Lifting Schemes for Quaternion-Based Attitude Control ∗

The unit quaternion is a pervasive representation of rigid-body attitude used for the design and analysis of feedback control laws. Often, quaternion-based feedback control laws require an additional mechanism that lifts a continuous attitude trajectory to the unit quaternion space. Lifting mechanisms that are memoryless, for example, selecting the quaternion having positive scalar component, have a limited domain where they remain injective and, when used globally, introduce discontinuities into the closed-loop system. We show that such discontinuities can be exploited by an arbitrarily small measurement disturbance to stabilize attitudes far from the desired attitude and destroy “global” attractivity properties.
A peptide encoded by human gene MAGE‐3 and presented by HLA‐A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE‐3

The human MAGE‐3 gene is expressed in many tumors of several histological types but it is silent in normal tissues, with the exception of testis. Antigens encoded by MAGE‐3 may, therefore, be useful targets for specific anti‐tumor immunization of cancer patients. We reported previously that MAGE‐3 codes for an antigenic peptide recognized on a melanoma cell line by autologous cytolytic T lymphocytes (CTL) restricted by HLA‐A1. Here we report that the MAGE‐3 gene also codes for another antigenic peptide that is recognized by CTL restricted by HLA‐A2. MAGE‐3 peptides bearing consensus anchor residues for HLA‐A2 were synthesized and tested for binding. T lymphocytes from normal individuals were stimulated with autologous irradiated lymphoblasts pulsed with each of three peptides that showed strong binding to HLA‐A2. Peptide FLWGPRALV was able to induce CTL. We obtained CTL clones that recognized not only HLA‐A2 cells pulsed with this peptide but also HLA‐A2 tumor cell lines expressing the MAGE‐3 gene. The proportion of melanoma tumors expressing this antigen should be approximately 32 % in Caucasian populations, since 49 % of individuals carry the HLA‐A2 allele and 65 % of melanomas express MAGE‐3.
Characterization of a Novel Simian Immunodeficiency Virus with a vpu Gene from Greater Spot-Nosed Monkeys (Cercopithecus nictitans) Provides New Insights into Simian/Human Immunodeficiency Virus Phylogeny

ABSTRACT In the present study, we describe a new simian immunodeficiency virus (SIV), designated SIVgsn, naturally infecting greater spot-nosed monkeys (Cercopithecus nictitans) in Cameroon. Together with SIVsyk, SIVgsn represents the second virus isolated from a monkey belonging to the Cercopithecus mitis group of the Cercopithecus genus. Full-length genome sequence analysis of two SIVgsn strains, SIVgsn-99CM71 and SIVgsn-99CM166, revealed that despite the close phylogenetic relationship of their hosts, SIVgsn was highly divergent from SIVsyk. First of all, they differ in their genomic organization. SIVgsn codes for a vpu homologue, so far a unique feature of the members of the SIVcpz/human immunodeficiency virus type 1 (HIV-1) lineage, and detailed phylogenetic analyses of various regions of the viral genome indicated that SIVgsn might be a mosaic of sequences with different evolutionary histories. SIVgsn was related to SIVsyk in Gag and part of Pol and related to SIVcpz in Env, and the middle part of the genome did not cluster significantly with any of the known SIV lineages. When comparing the two SIVgsn Env sequences with that of SIVcpz, a remarkable conservation was seen in the V3 loop, indicating a possible common origin for the envelopes of these two viruses. The habitats of the two subspecies of chimpanzees infected by SIVcpz overlap the geographic ranges of greater spot-nosed monkeys and other monkey species, allowing cross-species transmission and recombination between coinfecting viruses. The complex genomic structure of SIVgsn, the presence of a vpu gene, and its relatedness to SIVcpz in the envelope suggest a link between SIVgsn and SIVcpz and provide new insights about the origin of SIVcpz in chimpanzees.
Quantitative Evaluation of Hyaline Cartilage Disorders Using Flash Sequence

In a prospective clinical study 24 normal volunteers and 106 patients with acute and chronic arthritis, osteoarthritis and post-traumatic alterations of the knee joints were examined. Using the parameters A and M 98 per cent of the pathologic cartilages and 74 per cent of the normal cartilages could be identified. In addition 78.5 per cent were correctly categorized in 5 cartilage classes. The A/M classification proved to be a fast and specific method for evaluation of cartilage disorders with special promise for follow-up examinations during therapy.