Workload, general perceived stress, body function, musculoskeletal pain, and their mutual relationships in nurses - a pilot study.

OBJECTIVES: Both physical and psychosocial risk factors contributing to musculoskeletal disorders occur in the professional nursing group, and previous literature suggested that their interaction may increase the risk of musculoskeletal pain among nurses. The aim of the study was to examine perceived workload and stress as well as physical findings and musculoskeletal complaints in nurses. MATERIAL AND METHODS: The participants consisted of 42 female nurses, age range 23-60 years. They marked on a pain drawing the site/sites that was/were painful at the moment of testing, its duration and intensity. Thereafter they were examined using the movement and respiration domains from the Global Physiotherapy Examination (GPE). Furthermore, a subjective workload measure was made using the paper version of the National Aeronautics and Space Administration Task Load Index and stress was assessed using the Perceived Stress Questionnaire. RESULTS: Almost the entire study group declared that pain experienced in at least 1 location was chronic, i.e., had lasted ≥1 year (97%). The most frequent locations of pain were low back (22.4%) and cervical/head (21.6%) regions. In the GPE, most scores indicated restricted and reduced movement, with the subdomain flexibility having the highest deviation from the predefined standard. Furthermore, the results indicated hampered respiration, especially visible in standing position. Out of all workload scores, the highest was obtained for temporal demand. Perceived stress level was found to be moderate and significantly associated to chronic chest/ thoracic pain. Interestingly, the compression of thorax test positively correlated with mental (r = 0.42, p < 0.05) and physical demand (r = 0.35, p < 0.05), whereas the elbow drop test and temporal demand correlated negatively (r = -0.37, p < 0.05). CONCLUSIONS: To sum up, the majority of nurses participating in this study had long-lasting pain and limited flexibility of the body and hampered respiration, which both may enhance intensity of experienced musculoskeletal pain. Int J Occup Med Environ Health. 2024;37(3).

Esketamine inhaled as dry powder: Pharmacokinetic, pharmacodynamic and safety assessment in a preclinical study.

Ketamine and its enantiomer esketamine have gained much attention in recent years as potent, fast-acting agents for the management of treatment-resistant depression. However, an alternative to oral ketamine administration is required to ensure adequate systemic exposure as the drug undergoes extensive first-pass metabolism. We propose dry powder inhalation as a new esketamine delivery route. Here, we examine the pharmacokinetics, pharmacodynamics, toxicology and safety of this novel esketamine administration method. Esketamine (10 mg/kg) and ketamine racemate (20 mg/kg) were administered to rats by dry powder inhalation, intravenous injection or intratracheal instillation and the pharmacokinetics of these treatments were compared. Analyte concentration of ketamine stereoisomers and their metabolites was assessed by LC-MS/MS method. Esketamine showed a clinically relevant pharmacokinetic profile, with high bioavailability (62%) and relatively low maximum concentration peaks. Esketamine exhibited high penetration of the blood-brain barrier, but pharmacodynamic examinations of brain homogenates showed no changes in selected protein phosphorylation or expression analyzed by the immunoblotting method. We conducted GLP-compliant 14-day and 28-day general toxicity studies in rats and dogs, respectively, subjected to dry esketamine powder inhalation. The maximum daily dosages were 46.5 mg/kg and 36.5 mg/kg, respectively. We also performed pharmacological safety studies. Esketamine inhaled as dry powder had an expected safety profile consistent with its known pharmacological action. None of its observed effects were considered toxicologically significant. The pharmacological safety studies confirmed that the observed effects were transient and that inhaled esketamine had a good safety profile. Hence, our preclinical studies demonstrated that dry powder inhalation is a highly efficacious and safe delivery route for esketamine and may be a viable alternative administration route meriting further clinical development.

Does Walking Help to Generate a Differential Diagnosis?

TheoryIn Medicine, arriving at the correct diagnosis is of paramount importance for patient health and safety, yet is a difficult task especially when a patient presents with symptoms that do not fit typical patterns of disease. This task can be further complicated by errors of judgment, with the failure to consider all possible diagnoses being the most common of such errors. In this study, we investigated the process of differential diagnosis generation within the growing evidence that diagnostic performance can be increased by activities such as walking as was previously shown in Oppezzo and Schwartz's 2014 study. Hypotheses: It was hypothesized that an increase in performance, as expressed by a greater number of plausible differential diagnoses, would be seen in the walking group. Method: Eighteen medical students in their last two months of pre-clerkship training and eighteen second year family medicine residents were shown four different lists of a constellation of signs and symptoms. Participants were asked to generate differential diagnoses over five minutes per each list. All participants sat when completing the first two lists (pretest phase), and then were equally and randomly assigned to sitting versus walking on a treadmill when completing the last two lists (post-test phase). The number of total and unique differential diagnoses generated was determined, before being submitted to a three-member expert panel who identified appropriate unique differential diagnoses. Results: Two-way mixed ANOVAs were conducted to investigate the impact of exercise on the number of total, unique, and appropriate unique ideas generated and compared between pretest and post-test phases. Conclusions: We conclude that there is neither an increase nor a decrease in the number or quality of differential diagnoses generated by the sitting and walking groups within a population that has acquired some level of expertise.

Feasibility of Intradialytic Cycling Program in a Remote Community Hemodialysis Unit: Mixed-Methods Analysis of Implementation.

BACKGROUND: There is growing evidence demonstrating the benefits of intradialytic cycling. However, there are relatively few centers where this practice has been adopted with no reports from hemodialysis units in rural, remote, and northern locations. Maintaining mobility and quality of life for patients on kidney replacement therapy living in remote northern communities is inhibited by inclement weather and lack of access to resources and infrastructure that support physical activity. The integration of intradialytic cycling during hemodialysis offers patients a form of safe physical activity year-round. OBJECTIVE: This study focuses on better understanding the feasibility and acceptability of implementing intradialytic cycling in a remote northern geographical context. DESIGN: A feasibility study using a mixed-methods explanatory design was adopted for this study. SETTING: The research is conducted in Prince George, British Columbia. PARTICIPANTS: The participants are patients attending a community-based dialysis unit in remote northern British Columbia and health professionals working in the same facility. METHODS: Quantitative measures were captured through cycling logbooks and quality of life measure, and qualitative data were obtained through semi-structured interviews and analyzed using thematic analysis. RESULTS: Six (43%) eligible patients used leg ergometers more than once for a median of 2.5 (interquartile range: 1-4) months and 87% of hemodialysis sessions. Participants cycled for a median of 65 (interquartile range: 39-76) minutes per session, with frequent variability noted between participants and different hemodialysis sessions for the same participant. Nine patients completed the European Quality of Life Health Questionnaire prestudy, with 5 (56%) also completing it poststudy. Interviews with 9 patients, 4 nurses, and 1 physiotherapist led to the identification of themes instrumental to implementation: a supportive community dialysis unit, shared responsibility, knowledge of patients/providers, and benefits associated with engagement. Themes that were identified as being key to acceptability in this remote dialysis unit were trust, connection, and engagement through common values. LIMITATIONS: Due to dialysis unit size, we had a small number of participants. CONCLUSIONS: This study demonstrates the feasibility of implementing best practice in a remote community and provides insight into the elements of context and participation that contribute to acceptability in the implementation of intradialytic cycling.

CONTEXTE: De plus en plus d'études attestent des bienfaits du cyclisme intradialytique. Relativement peu de centres ont cependant adopté cette pratique et aucun rapport ne fait état de son intégration dans les unités d'hémodialyse des régions rurales, éloignées et nordiques. Dans ces communautés, les conditions météorologiques défavorables et le manque d'accès aux ressources et aux infrastructures encourageant l'activité physique sont une entrave au maintien de la mobilité et de la qualité de vie des patients sous thérapie de remplacement rénal. L'intégration du cyclisme intradialytique permettrait aux patients de pratiquer une forme d'activité physique sécuritaire à longueur d'année. OBJECTIFS: L'étude examine la faisabilité et l'acceptabilité relativement à l'instauration du cyclisme intradialytique dans l'unité d'hémodialyse d'une région géographique nordique éloignée. TYPE D'ÉTUDE: Étude de faisabilité à visée explicative utilisant une méthode mixte. CADRE: L'étude est menée à Prince George, en Colombie-Britannique. PARTICIPANTS: Des patients qui fréquentent une unité de dialyse communautaire dans le nord de la Colombie-Britannique et des professionnels de la santé qui travaillent dans le même établissement. MÉTHODOLOGIE: Les mesures quantitatives ont été saisies au moyen de carnets de bord de cyclisme et de mesures de la qualité de vie. Les données qualitatives ont été obtenues au moyen d'entrevues semi-structurées et analysées à l'aide d'analyses thématiques. RÉSULTATS: Les résultats portent sur les six (43 %) patients admissibles ayant utilisé une bicyclette ergométrique plus d'une fois pendant une médiane de 2,5 mois (intervalle interquartile : 1-4 fois) et 87 % des séances d'hémodialyse. Les participants ont pédalé 65 minutes en moyenne (intervalle interquartile : 39-76 minutes) par séance; de fréquentes variations ayant été observées entre les participants et entre les différentes séances d'hémodialyse pour un même participant. Neuf patients ont rempli le questionnaire européen sur la qualité de vie et la santé avant l'étude et cinq patients (56 %) l'ont fait après l'étude. Des entrevues avec neuf patients, quatre infirmières et un physiothérapeute ont permis de dégager les thèmes essentiels pour l'instauration du cyclisme intradialytique : un environnement favorable dans l'unité de dialyse communautaire, une responsabilité partagée, la connaissance des patients/fournisseurs de soins et les bienfaits associés à l'engagement. Les thèmes jugés essentiels à l'acceptabilité dans l'unité de dialyse examinée étaient la confiance, l'établissement d'une bonne relation et l'engagement par le biais de valeurs communes. LIMITES: La taille de l'unité de dialyse explique le faible nombre de participants. CONCLUSION: Cette étude démontre qu'il est possible d'instaurer de meilleures pratiques dans une communauté éloignée. Elle donne également un aperçu des éléments de contexte et de participation qui favorisent l'acceptabilité du cyclisme intradialytique.

CPL207280, a Novel G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1-Specific Agonist, Shows a Favorable Safety Profile and Exerts Antidiabetic Effects in Type 2 Diabetic Animals.

G protein-coupled receptor (GPR) 40 is a free fatty acid receptor mainly expressed in pancreatic ß-cells activated by medium- and long-chain fatty acids and regulating insulin secretion via an increase in cytosolic free calcium ([Ca2+]i). Activation of GPR40 in pancreatic ß-cells may improve glycemic control in type 2 diabetes through enhancement of glucose-stimulated insulin secretion. However, the most clinically advanced GPR40 agonist-TAK-875 (fasiglifam)-was withdrawn from phase III because of its hepatotoxicity resulting from the inhibition of pivotal bile acid transporters. Here, we present a new, potent CPL207280 agonist and compare it with fasiglifam in numerous in vitro and in vivo studies. CPL207280 showed greater potency than fasiglifam in a Ca2+ influx assay with a human GPR40 protein (EC50 = 80 vs. 270 nM, respectively). At the 10 µM concentration, it showed 3.9 times greater enhancement of glucose-stimulated insulin secretion in mouse MIN6 pancreatic ß-cells. In Wistar Han rats and C57BL6 mice challenged with glucose, CPL207280 stimulated 2.5 times greater insulin secretion without causing hypoglycemia at 10 mg/kg compared with fasiglifam. In three diabetic rat models, CPL207280 improved glucose tolerance and increased insulin area under the curve by 212%, 142%, and 347%, respectively. Evaluation of potential off-target activity (Safety47) and selectivity of CPL207280 (at 10 µM) did not show any significant off-target activity. We conclude that CPL207280 is a potent enhancer of glucose-stimulated insulin secretion in animal disease models with no risk of hypoglycemia at therapeutic doses. Therefore, we propose the CPL207280 compound as a compelling candidate for type 2 diabetes treatment. SIGNIFICANCE STATEMENT: GPR40 is a well-known and promising target for diabetes. This study is the first to show the safety and effects of CPL207280, a novel GPR40/free fatty acid receptor 1 agonist, on glucose homeostasis both in vitro and in vivo in different diabetic animal models. Therefore, we propose the CPL207280 compound as a novel, glucose-lowering agent, overcoming the unmet medical needs of patients with type 2 diabetes.

The Influence of Mechanical Alloying and Plastic Consolidation on the Resistance to Arc Erosion of the Ag-Re Composite Contact Material.

The article presents the influence of mechanical alloying and plastic consolidation on the resistance to arc erosion of the composite Ag-Re material against the selected contact materials. The following composites were selected for the tests: Ag90Re10, Ag95Re5, Ag99Re1 (bulk chemical composition). Ag-Re materials were made using two methods. In the first, the materials were obtained by mixing powders, pressing, sintering, extrusion, drawing, and die forging, whereas, in the second, the process of mechanical alloying was additionally used. The widely available Ag(SnO2)10 and AgNi10 contact materials were used as reference materials. The reference AgNi10 material was made by powder metallurgy in the process of mixing, pressing, sintering, extrusion, drawing, and die forging, while the Ag(SnO2)10 composite was obtained by spraying AgSniBi alloy with water, and then the powder was pressed, oxidized internally, sintered, extruded into wire, and drawn and die forged. The tests of electric arc resistance were carried out for loads with direct current (DC) and alternating current (AC). For alternating current (I = 60 A, U = 230 V), 15,000 switching cycles were made, while, for constant current 50,000 (I = 10 A, U = 550 V). A positive effect of the mechanical alloying process and the addition of a small amount of rhenium (1% by mass) on the spark erosion properties of the Ag-Re contact material was found. When DC current of 10 A was used, AgRe1 composite was found to be more resistant than commonly used contact materials (AgNi10 and Ag(SnO2)10).

Does walking improve diagnosis of skin conditions at varying levels of medical expertise?

The use of walking workstations in educational and work settings has been shown to improve cognitive abilities. At the same time, it has been repeatedly shown that medical residents around the world do not meet exercise guidelines, mainly due to a scarcity of available free time. Our study investigates the boundaries of the previously observed phenomenon of improved cognitive performance with physical activity using materials that represent real life tasks. Participants had different level of expertise and involved second year psychology students, medical students, and family medicine residents. We examined the effect of being physically inactive (i.e., sitting) or active (i.e., walking) while diagnosing multiple complex presentations of four skin conditions. We assumed that being physically active, irrespective of the level of expertise, will bolster diagnostic performance. Our findings show, however, that being physically active does not change the performance level of participants with different levels of medical expertise. Implications for medical education and suggestions for further research will be discussed.

The Relationship Between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead.

The purpose of this work was to assess the influence of selected CNR1, MC4R, LEP, FTO and VDR FOKI gene polymorphisms on blood and urine concentration markers of lead, cadmium and arsenic in a population directly exposed to these metals. Eighty-five people exposed to lead, arsenic and cadmium were qualified to take part in the study. Standard urine samples and 25mL of venous blood from each worker were collected to assay basic laboratory and toxicological markers as well as selected single nucleotide polymorphisms (SNPs) within CNR1-cannabinoid receptor 1 gene (rs806368, rs806381, rs1049353, rs12720071), MC4R-melanocortin 4 receptor gene (rs17782313), LEP-leptin promoter gene (rs7799039), FTO-alpha-ketoglutarate-dependent dioxygenase gene (rs9939609) and VDR-vitamin D receptor (rs10735810) genes. It appeared that, except for the MC4R SNP, all the other polymorphisms were found to be associated with various laboratory parameters. Arsenic concentration in urine was associated with all four CNR1 and LEP SNPs, while cadmium concentration in blood was affected by the VDR polymorphism. Moreover, some significant relationships were also observed between CNR1 rs1049353 and FTO rs9939609 gene variants and markers of lead exposure. These results imply SNPs within genes coding for proteins involved in development of metabolic syndrome may be of prognostic value for persons directly exposed to lead, cadmium and arsenic.

Novel engineered TRAIL-based chimeric protein strongly inhibits tumor growth and bypasses TRAIL resistance.

Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD-O51.4, which is a TRAIL equipped with positively charged VEGFA-derived effector peptides. The study was performed in multiple cancer cell line- and patient-derived xenografts. A pharmacokinetic profile was established in monkeys. AD-O51.4 strongly inhibits tumor growth, even leading to complete long-term tumor remission. Neither mice nor monkeys treated with AD-O51.4 demonstrate symptoms of drug toxicity. AD-O51.4 exhibits a satisfactory half-life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD-O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD-O51.4-driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL-sensitive and TRAIL-resistant cancer cells, respectively. The FADD-dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD-O51.4 is capable of bypassing the refractoriness of TRAIL. AD-O51.4-driven cell death, which exceeds TRAIL activity, is achieved due to the N-terminally fused polypeptide, containing VEGFA-derived effector peptides. The high anticancer efficiency of AD-O51.4 combined with its safety has led to the entry of AD-O51.4 into toxicological studies.

Magnetocaloric Properties of Mn1.1Fe0.9P0.5As0.5-xGex (0 ≤ x ≤ 0.1) Compounds.

Intermetallic compounds with the overall formula Mn1.1Fe0.9P0.5As0.5-xGex (x varies from 0 to 0.1) were investigated in order to study their magnetocaloric effect by monitoring the adiabatic temperature change, magnetic entropy change and their relation to structural parameters. It was found that the maximum of magnetocaloric effect was achieved for x = 0.02. Adiabatic temperature change for consolidated powder was equal to 2.75 K for the magnetic field change ΔB = 1.7 T for the sample with x = 0.02. For the pure non-doped sample, this parameter is much lower: ΔTad = 1.7 K @ ΔB = 1.7 T. This result was correlated with the change of structural parameters such as lattice constants and the unit cell volume.

Quality of life and health behaviours of patients with tuberculosis - sex differences.

INTRODUCTION: Despite the introduction of effective antituberculosis drugs, tuberculosis (TB) is still a serious health problem and one of the most significant causes of death among infectious diseases. Current publications indicate an increase of tuberculosis cases among smokers, diabetics, malnurished subjects and those abusing alcohol and drugs. In the literature, there are only few studies raising the topic of the quality of life (QoL), stress management and health behaviour among patients with tuberculosis. The aim of this study was to evaluate QoL of patients with tuberculosis taking into account gender differences. In the study, the analysis of knowledge, health behaviour and stress management among TB patients depending on sex was carried out. MATERIAL AND METHODS: The study included 80 subjects diagnosed with TB (including 38 females) who were hospitalised at the Regional Hospital Centre of Kotlina Jeleniogórska, Medical Unit Wysoka Laka, Pulmonology and Phthisiology Department in Kowary between August 2012 and January 2013. The following questionnaires were used in the study: Mini-COPE - evaluating stress management, WHOQoL - assessing the quality of life of patients, IZZ - assessing health behaviour. RESULTS: A difference with regards to sociodemographic profile between females and males was observed. Half of the women surveyed were working (50% vs 19% of men), whereas half of men were entitled to unemployment benefit (50% vs 18.4% of women). More than half of women lived with their family (55.3%), whereas 47.6% of men lived alone. The majority of the subjects consumed alcohol occasionally (60.2% of women vs 45.2% of men), but as many as 31% of male patients vs 7.9% of females admitted that they consumed alcohol frequently. Among the respondents, people who consumed alcohol occasionally dominated (60.2% women vs. 45.2% of men), but as many as 31% of male patients vs. 7.9% of women admitted to consume alcohol frequently. Quality of life (QoL) assessment has shown no statistically significant differences between the sexes in this field. The respondents rated lowest their QoL in the physical domain, 12.4 ± 3.1 (12.9 ± 3.0 women vs. 11.8 ± 3.1 men) and 12.6 ± 2.4 in the environmental domain (13.1 ± 2.3 women vs 12.1± 2.4 men). Women received a higher rating of health behaviour on all subscales of the IZZ questionnaire, with the highest score in the prevention behaviour subscale (3.6 ± 0.7) and the lowest in the subscale of proper eating habits (3.1 ± 0.8). In men the highest score of health behaviour was observed in the subscale of positive mental attitude (3.1 ± 1.0) and the lowest in the subscale of proper eating habits (2.5 ± 0.8). CONCLUSIONS: 1. There are differences between sociodemographic profile of TB patients: women are younger, better educated, economically active and more likely to remain in relationships; 2. There is no difference in QoL of TB patients between the sexes, whereas there are differences in the strategies of stress management and in applied health behavior; 3. Differences between genders indicate the need for matching treatment and preventive action for different patients profiles based on the cooperation of doctors, social workers, therapists, and psychologists.

Cognitive load imposed by knobology may adversely affect learners' perception of utility in using ultrasonography to learn physical examination skills, but not anatomy.

Ultrasonography is increasingly used for teaching anatomy and physical examination skills but its effect on cognitive load is unknown. This study aimed to determine ultrasound's perceived utility for learning, and to investigate the effect of cognitive load on its perceived utility. Consenting first-year medical students (n = 137) completed ultrasound training that includes a didactic component and four ultrasound-guided anatomy and physical examination teaching sessions. Learners then completed a survey on comfort with physical examination techniques (three items; alpha = 0.77), perceived utility of ultrasound in learning (two items; alpha = 0.89), and cognitive load on ultrasound use [measured with a validated nine-point scale (10 items; alpha = 0.88)]. Learners found ultrasound useful for learning for both anatomy and physical examination (mean 4.2 ± 0.9 and 4.4 ± 0.8, respectively; where 1 = very useless and 5 = very useful). Principal components analysis on the cognitive load survey revealed two factors, "image interpretation" and "basic knobology," which accounted for 60.3% of total variance. Weighted factor scores were not associated with perceived utility in learning anatomy (beta = 0.01, P = 0.62 for "image interpretation" and beta = -0.04, P = 0.33 for "basic knobology"). However, factor score on "knobology" was inversely associated with perceived utility for learning physical examination (beta = -0.06; P = 0.03). While a basic introduction to ultrasound may suffice for teaching anatomy, more training may be required for teaching physical examination. Prior to teaching physical examination skills with ultrasonography, we recommend ensuring that learners have sufficient knobology skills.

AD-O53.2--a novel recombinant fusion protein combining the activities of TRAIL/Apo2L and Smac/Diablo, overcomes resistance of human cancer cells to TRAIL/Apo2L.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors became promising molecules for selective targeting of tumor cells without affecting normal tissue. Unfortunately, cancer cells have developed a number of mechanisms that confer resistance to TRAIL\Apo2L-induced apoptosis, which substantiates the need for development of alternative therapeutic strategies. Here we present a recombinant variant of TRAIL\Apo2L peptide, named AD-O53.2, fused to the peptide-derived from Smac/Diablo protein-the natural inhibitor of the apoptotic X-linked IAP (XIAP) protein considered as a pro-apoptotic agent. The proposed mechanism of action for this construct involves specific targeting of the tumor by TRAIL\Apo2L followed by activation and internalization of pro-apoptotic peptide into the cancer cells. While in the cytoplasm , the Smac\Diablo peptide inhibits activity of X-linked IAP (XIAP) proteins and promotes caspase-mediated apoptosis. AD-O53.2 construct was expressed in E.coli and purified by Ion Exchange Chromatography (IEC). Derived protein was initially characterized by circular dichroism spectroscopy (CD), HPLC-SEC chromatography, surface plasmon resonance, protease activation and cell proliferation assays. Our Smac/Diablo-TRAIL fusion variant was tested against a panel of cancer cells (including lung, colorectal, pancreatic, liver, kidney and uterine) and showed a potent cytotoxic effect with the IC50 values in femtomolar range for the most sensitive cell lines, while it remained ineffective against non-transformed HUVEC cells as well as isolated normal human and rat hepatocytes. Importantly, the construct was well tolerated by animals and significantly reduced the rate of the tumor growth in colon and lung adenocarcinoma animal models.

Medical educators' perspectives of teaching physical examinations using ultrasonography at the undergraduate level.

BACKGROUND: Ultrasonography is increasingly used for teaching physical examination in medical schools. This study seeks the opinions of educators as to which physical examinations would be most enhanced by the addition of ultrasonography. We also asked when ultrasound-aided physical examination teaching could have deleterious effects if used outside its intended scope. METHODS: All of the educators from the University of Calgary Master Teacher Program were invited to complete a 22-item paper-based survey. Survey items were generated independently by two investigators, with input from an expert panel (n = 5). RESULTS: Of the 36 educators, 27 (75%) completed the survey. Examinations identified to be potentially most useful included: measuring the size of the abdominal aorta, identifying the presence/absence of ascites, identifying the presence/absence of pleural effusions, and measuring the size of the bladder. Examinations thought to be potentially most harmful included: identifying the presence/absence of intrauterine pregnancy, measuring the size of the abdominal aorta, and identifying the presence/absence of pericardial effusion. CONCLUSIONS: Examinations that are potentially the most useful may also be potentially the most harmful. When initiating an ultrasound curriculum for physical examinations, educators should weigh the risks and benefits of examinations chosen.

Killer immunoglobulin-like receptor (KIR) and HLA genotypes affect the outcome of allogeneic kidney transplantation.

BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self) HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs). KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.