Ireland's Assisted Decision Making Capacity Act-the potential for unintended effects in critical emergencies: a cross-sectional study of Advanced Paramedic decision making.
Irish legislation on Advance Healthcare Directives (Assisted Decision Making Capacity Act 2015, ADMC) proposes to change the basis of decision making from acting in the patient's best interests to following the expressed will and intentions of the patient. Refusal of life-saving care can occur, without sound reasons. The implications for care in life-threatening emergencies have not been explored among clinicians. An anonymous questionnaire survey of Advanced Paramedics (AP) covering awareness of the legislation, attitudes to and experience of refusal of care and potential actions in emergency scenarios now and if the legislation were in force. The scenarios covered end-of-life and deliberate self-harm situations potentially requiring resuscitation. All 482 graduates of the Advanced Paramedic Training Programme were invited to take part. Overall, 85/389 (21.9%) valid contacts responded, with demographic characteristics similar to the overall population. Attitudes ranged from highly positive to highly negative in relation to the potential impact of the legislation on professional and operational responsibilities. Respondents described marked changes in whether they would offer resuscitation if the ADMC were in place. Irish legislation which changes the traditional basis of medical practice away from the best interests of the patient may affect the resuscitation practices of Advanced Paramedics in life-threatening situations. It has significant implications for medical education, professional practice and clinician-patient interactions. This legislation and similar planned legislation may have implications for other EU jurisdictions.


Novel student roles in health care delivery: An example emerging from the COVID-19 health care crisis in 2021.
In 2021, the rapid rise in COVID-19 infections put overwhelming demand on health care services. It was recognised that patients could be managed in the community if an appropriate monitoring service existed. Medical students were recruited for roles that combined technology, teamwork and clinical skills. This is an example of how novel roles can provide solutions in times of health care crises.


Human B lymphocytes and thymocytes but not peripheral blood mononuclear cells accumulate high dATP levels in conditions simulating ADA deficiency.
Inherited adenosine deaminase (ADA) deficiency is associated with a lymphospecific cytotoxicity affecting both dividing and non-dividing cells. The metabolic basis for this was investigated using different cell types and the potentially toxic metabolite 2'-deoxyadenosine (dAR) in short-term experiments under physiological conditions simulating ADA deficiency (1 mM Pi 8.7 microM dAR). In the uncultured cells, [8-14C] dAR alone was metabolized almost completely only by thymocytes and tonsil-derived B-lymphocytes. The greater percentage of counts (greater than 75%) were in the medium (deoxyinosine, hypoxanthine). Cellular counts were predominantly in adenine nucleotides, and to a lesser extent guanine nucleotides. Interestingly, both thymocytes and tonsil-derived B-lymphocytes, and a partially ADA deficient B lymphoblast line, accumulated detectable amounts of dATP even in the absence of ADA inhibition. Peripheral blood lymphocytes (PBMs) did not, and showed little dAR metabolism. In experiments simulating ADA deficiency varying amounts of 2'-deoxycoformycin (2'dCF) were needed to completely inhibit ADA (20-60 microM), with thymocytes requiring the highest amount. ADA inhibited thymocytes and tonsillar B-lymphocytes accumulated very high dATP levels, which were sustained to an equal extent by both over a 60-min period; PBMs accumulated the lowest values. Results in cultured cells reflected findings in previous studies. Some counts were also found in ATP by a route excluding ADA or PNP. These results again question the hypothesis that B-cells are more resistant than T-cells to the toxic effects of dAR because of an inability to accumulate and sustain elevated dATP levels and underline the lack of comparability between enzyme activity in intact as distinct from lysed cells. They cast doubt on the validity of cultured cells as a model for ADA deficiency and suggest the observed toxicity in some instances might result from altered ATP or GTP pools through inadequate ADA inhibition. They indicate that combined immunodeficiency in ADA deficiency could relate to an equal sensitivity of B-cells and T-cell precursors to the toxic effects of dATP accumulation.


Single particle detection of Abeta aggregates associated with Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Today, AD can be diagnosed with certainty only post-mortem, by histopathologic staining of Abeta plaques and neurofibrillary tangles in brain tissue sections. We have developed an ultra-sensitive assay potentially suitable for early and non-invasive diagnosis of AD. This highly specific and sensitive assay uses fluorescence correlation spectroscopy (FCS) and is sensitive enough to detect even single aggregates in body fluids of AD patients. First results show a clear distinction between AD diseased people and non-demented controls by analysing cerebrospinal fluids (CSF) by confocal scanning of surface captured Abeta aggregates and subsequent two-dimensional fluorescence intensity distribution analysis.


Comparison of mu opioid receptors in brains of rats bred for high or low rate of self-stimulation.
Opiates and endogenous opioid peptides play an important role in reward-mediated behaviors, including self-stimulation. Two strains of rats, LC2-Hi and LC2-Lo, selectively bred for high vs. low rate of lateral hypothalamic self-stimulation, were employed in the present study. Quantitative autoradiography was performed on brains of adult male rats of each strain, using the mu opioid receptor agonist 3H-DAGO. Strain differences in receptor density were observed in the nucleus accumbens and in ventral areas of the hippocampus.


[Reduced emergency room time for trauma patients by integrated CT].
A new emergency room (ER) has been established in our trauma centre including an integrated CT scanner. The former ER was located at a long distance from the CT. The aim of this study was to evaluate the influence of the integrated CT in the new ER on the time period from hospital admission to CT diagnostics as well as on the total ER time period. Data from the old ER (2005-2007) have been compared with those from the new ER (2009). All patients whose data have been transmitted to the German Trauma Registry (DGU) have been included. For statistics the Mann-Whitney U test has been used. Data of 457 patients could be included. Time from admission to CT scan in the old ER had an average of 35 ± 27 min (4-240 min), in the new ER 13 ± 10 min (1-67 min; p < 0.001). The total ER time could be reduced from 86 ± 42 min (10-240) in the old ER to 61 ± 33 min (5-190; p < 0.001) in the new ER. Time from hospital admission to CT scan as well as the total ER time period can be reduced by using an integrated CT scanner.


Exercise Stress Echocardiography in Kawasaki Disease Patients with Coronary Aneurysms.
The most significant sequelae of Kawasaki disease (KD) are coronary artery aneurysms, which can lead to risk of future myocardial ischemia. Exercise stress echocardiography allows for non-invasive assessment of myocardial dysfunction. We reviewed our single center experience with exercise stress echocardiography in patients with previous history of KD with coronary aneurysms. We reviewed the records of 53 KD patients who underwent exercise stress echocardiography from 2000 to 2020. Abnormal stress echocardiograms were defined as those showing no increase in biventricular systolic function post-exercise or regional wall motion abnormalities. Computed tomography angiography and cardiac magnetic resonance imaging were reviewed for patients with abnormal stress echocardiograms. Clinical data were reviewed and correlated with stress echocardiogram results. Of the 53 patients, three (5.7%) had an abnormal exercise stress echocardiogram. All three patients were classified as AHA Risk Level 4 or 5 by coronary Z-score (internal dimension normalized for body surface area) and were confirmed to have coronary aneurysms, stenosis, or myocardial tissue perfusion defects on advanced cardiac imaging that could account for the results seen on stress echocardiogram. Exercise stress echocardiography detected signs of myocardial ischemia in a subset of high-risk patients with Kawasaki disease and coronary aneurysms and may be considered as a useful screening tool for this complex patient cohort.


Sample size calculation for clustered survival data under subunit randomization.
Each cluster consists of multiple subunits from which outcome data are collected. In a subunit randomization trial, subunits are randomized into different intervention arms. Observations from subunits within each cluster tend to be positively correlated due to the shared common frailties, so that the outcome data from a subunit randomization trial have dependency between arms as well as within each arm. For subunit randomization trials with a survival endpoint, few methods have been proposed for sample size calculation showing the clear relationship between the joint survival distribution between subunits and the sample size, especially when the number of subunits from each cluster is variable. In this paper, we propose a closed form sample size formula for weighted rank test to compare the marginal survival distributions between intervention arms under subunit randomization, possibly with variable number of subunits among clusters. We conduct extensive simulations to evaluate the performance of our formula under various design settings, and demonstrate our sample size calculation method with some real clinical trials.


Ultrashort Echo-Time MR Imaging of the Pediatric Head and Neck.
Bone MR imaging techniques use extremely rapid echo times to maximize detection of short-T2 tissues with low water concentrations. The major approaches used in clinical practice are ultrashort echo-time and zero echo-time. Synthetic CT generation is feasible using atlas-based, voxel-based, and deep learning approaches. Major clinical applications in the pediatric head and neck include evaluation for craniosynostosis, sinonasal and jaw imaging, trauma, interventional planning, and postoperative follow-up. In this article, we review the technical background and practical usefulness of bone MR imaging with key imaging examples.


Operation of a P300-based brain-computer interface by patients with spinocerebellar ataxia.
We investigated the efficacy of a P300-based brain-computer interface (BCI) for patients with spinocerebellar ataxia (SCA), which is often accompanied by cerebellar impairment. Eight patients with SCA and eight age- and gender-matched healthy controls were instructed to input Japanese hiragana characters using the P300-based BCI with green/blue flicker. All patients depended on some assistance in their daily lives (modified Rankin scale: mean 3.5). The chief symptom was cerebellar ataxia; no cognitive deterioration was present. A region-based, two-step P300-based BCI was used. During the P300 task, eight-channel EEG data were recorded, and a linear discriminant analysis distinguished the target from other nontarget regions of the matrix. The mean online accuracy in BCI operation was 82.9% for patients with SCA and 83.2% for controls; no significant difference was detected. The P300-based BCI was operated successfully not only by healthy controls but also by individuals with SCA. These results suggest that the P300-based BCI may be applicable for patients with SCA.


Screening of organic and metal contaminants in Australian humpback dolphins (Sousa sahulensis) inhabiting an urbanised embayment.
As a marine mammal species that inhabits shallow nearshore waters, humpback dolphins are likely exposed to a wide range of pollutants from adjacent land-based activities. Increased mortality rates of Australian humpback dolphins (Sousa sahulensis) in waters off a major urbanised centre triggered investigations into the threats to these species, including their contaminant exposure. The present study utilised archived tissues from 6 stranded animals to screen for a range of pollutants (PCDD/Fs, PBDEs, PCBs, organochlorine pesticides, PAHs, organotins, essential and non-essential elements) to inform future biopsy based biomonitoring strategies. Concentrations of PCBs and DDXs in blubber of some of these animals were remarkably high, at levels near or above toxicological thresholds associated with immune- and reproductive toxicity or population declines in other marine mammals. PBDEs, PAHs, HCB, organotins, 'drins' as well as other organic pesticides were not detected, or present at relatively low concentrations. Profiles of elements were similar in epidermis compared to other tissues, and apart from some exceptions (e.g. Fe, Cr, Co, Cu) their concentrations fell within 25th-75th percentiles of cetacean baselines in four of the five animals. Non-essential elements (Al, V, Pb, Ba, Ni, Cd) were notably elevated in one specimen which may have experienced poor health or nutritional status. These data provide a first insight into the contaminant status of a rare and poorly studied population inhabiting an urbanised area. The results highlight a need for future biomonitoring of live populations, and inform on priorities in the typically limited blubber and skin sample volumes obtained through biopsies.


Best Practices for the Prevention of Radial Artery Occlusion After Transradial Diagnostic Angiography and Intervention: An International Consensus Paper.
Transradial access (TRA) is increasingly used worldwide for percutaneous interventional procedures and associated with lower bleeding and vascular complications than transfemoral artery access. Radial artery occlusion (RAO) is the most frequent post-procedural complication of TRA, restricting the use of the same radial artery for future procedures and as a conduit for coronary artery bypass graft. The authors review recent advances in the prevention of RAO following percutaneous TRA diagnostic or interventional procedures. Based on the available data, the authors provide easily applicable and effective recommendations to prevent periprocedural RAO and maximize the chances of access in case of repeat catheterization or coronary artery bypass grafting surgery.


Are rice (Oryza sativa L.) phosphate transporters regulated similarly by phosphate and arsenate? A comprehensive study.
Rice is one of the most important staple foods worldwide, but it often contains inorganic arsenic, which is toxic and gives rise to severe health problems. Rice plants take up arsenate As(V) via the phosphate transport pathways, though it is not known how As(V), as compared to phosphate, modifies the expression of phosphate transporters (PTs). Therefore, the impact of As(V) or phosphate (Pi) on the gene expression of PTs and several Pi signaling regulators was investigated. Rice plants were grown on medium containing different As(V) or Pi concentrations. Growth was evaluated and the expression of tested genes was quantified at different time points, using quantitative RT-PCR (qPCR). The As and P content in plants was determined using inductively coupled plasma mass spectrometry (ICP-MS). As(V) elicited diverse and opposite responses of different PTs in roots and shoots, while Pi triggered a more shallow and uniform transcriptional response in several tested genes. Only a restricted set of genes, including PT2, PT3, PT5 and PT13 and two SPX-MFS family members, was particularly responsive to As(V). Despite some common reactions, the responses of the analyzed genes were predominantly ion-specific. The possible reasons and consequences are discussed.


Necrotizing fasciitis in patients who underwent renal transplantation.
A 48-year-old man receiving renal transplantation was admitted due to bacterial pneumonia. Unfortunately, he developed septic shock due to Escherichia coli-related necrotizing fasciitis (NF). To date, there have only been 11 such cases reported in the literature and this is the first case caused by E coli. An analysis of all 12 cases showed 83% of patients had the infection in the extremities, 27.3% of pathogens was Streptococcus pyogenes, 50% of patients had shock, but the mortality rate (16.7%) was no greater than that seen in non-renal transplant patients with NF. The elderly had higher mortality (P = .085) and patients taking mycophenoic acid had a higher risk of death (P = .039).


Suitability of different growth substrates as source of nitrogen for sulfate reducing bacteria.
Sulfate reducing bacteria (SRB) mediated treatment of acid mine drainage is considered as a globally accepted technology. However, inadequate information on the role of nitrogen source in the augmentation of SRB significantly affects the overall treatment process. Sustenance of SRB depends on suitable nitrogen source which is considered as an important nutrient. This review focuses on the different nitrogen rich growth substrates for their effectiveness to support SRB growth and sulfate reduction in passive bioreactors. Compounds like NH4Cl, NH4HCO3, NO3 (-), aniline, tri-nitrotoluene, cornsteep liquor, peptone, urea, and chitin are reported to have served as nitrogen source for SRB. In association with fermentative bacteria, SRB can metabolize these complex compounds to NH4 (+), amines, and amino acids. After incorporation into cells, these compounds take part in the biosynthesis of nucleic acids, amino acids and enzyme co-factor. This work describes the status of current and the probable directions of the future research.


Ferrioxamine and its hexadentate iron-chelating metabolites in human post-desferal urine studied by high-performance liquid chromatography and fast atom bombardment mass spectrometry.
Three iron-containing fractions were detected by high-performance liquid chromatography (HPLC) on a reverse-phase column in the 24-h urine of two patients with hereditary hemochromatosis following the injection of deferoxamine mesylate (Desferal). These fractions have virtually identical absorption spectra in the visible range, with a broad maximum around 430 nm. Molecular weight determination of these fractions was performed by fast atom bombardment mass spectrometry (FAB-MS), which gave intense ion signals for the protonated molecular ions of the intact iron chelates, namely, at m/z 614 for ferrioxamine (FOA; Mr 613), at m/z 629 for metabolite I (FOA-MI; Mr 628), and at m/z 601 for metabolite II (FOA-MII; Mr 600). The molecular weight of FOA-MI is compatible with deamination of the terminal amino function and oxidation of the adjacent carbon atom to a carboxyl group; the molecular weight of FOA-MII is compatible with loss of a C2H4 unit from FOA-MI by beta oxidation. Quantification of iron in post-Desferal urine samples either by atomic absorption spectrometry (AAS) or by HPLC leads to results which are identical within experimental error. In ten subsequent 12-h urine samples of a patient under therapy (subcutaneous infusion of Desferal), the following distribution of urinary iron was found: FOA-MI, 58.4 +/- 4.7% (arithmetic mean +/- SD); FOA, 33.2 +/- 4.9%; FOA-MII, 8.4 +/- 1.7%. Addition of 2 mM ethylenediaminetetraacetic acid (EDTA) to the chromatographic solvents was used as a stability test for FOA and its two metabolites MI and MII.(ABSTRACT TRUNCATED AT 250 WORDS)


Musicians demonstrate experience-dependent brainstem enhancement of musical scale features within continuously gliding pitch.
In contrast to language, where pitch patterns consist of continuous and curvilinear contours, musical pitch consists of relatively discrete, stair-stepped sequences of notes. Behavioral and neurophysiological studies suggest that both tone-language and music experience enhance the representation of pitch cues associated with a listener's domain of expertise, e.g., curvilinear pitch in language, discrete scale steps in music. We compared brainstem frequency-following responses (FFRs) of English-speaking musicians (musical pitch experience) and native speakers of Mandarin Chinese (linguistic pitch experience) elicited by rising and falling tonal sweeps that are exemplary of Mandarin tonal contours but uncharacteristic of the pitch patterns typically found in music. In spite of musicians' unfamiliarity with such glides, we find that their brainstem FFRs show enhancement of the stimulus where the curvilinear sweep traverses discrete notes along the diatonic musical scale. This enhancement was note specific in that it was not observed immediately preceding or following the scale tone of interest (passing note). No such enhancements were observed in Chinese listeners. These findings suggest that the musician's brainstem may be differentially tuned by long-term exposure to the pitch patterns inherent to music, extracting pitch in relation to a fixed, hierarchical scale.


Developing an interpretation bias modification training task for alleviating loneliness in young people.
Loneliness is common among young people and is associated with negative health outcomes. Because loneliness is associated with a bias for interpreting social situations as threatening, cognitive bias modification for interpretation (CBM-I) training is a potential early intervention tool. We developed and delivered a single session of mental imagery enhanced digital CBM-I training, assessing feasibility, acceptability, and magnitude of change in interpretational style and loneliness. CBM-I training materials were developed using a co-creation approach with 18-25-year-olds with experience of loneliness. Another group of 18-25-year-olds with high loneliness received either online CBM-I (n = 29) or control (n = 27) training. CBM-I training uptake and retention rates were 88% and 92%, respectively. Participants found the training acceptable. The CBM-I group showed a reduction in social threat interpretations (d = 0.77), an increase in social benign interpretations (d = 0.84), and a decrease in loneliness (d = 0.56). The control group showed a small reduction in social threat interpretations (d = 0.21), no change in social benign interpretations (d = 0.04), and an increase in loneliness (d = 0.41). Interpretation biases relevant to youth loneliness may be modifiable, and CBM-I training could reduce feelings of loneliness. This informs psychological models of loneliness, and the development of CBM-I interventions targeting loneliness in young people.


Ghrelin is present in human colostrum, transitional and mature milk.
Ghrelin and its mRNA have recently been found in numerous human tissues including breast. The aim of this study was to compare the ghrelin levels in colostrum, mature and transitional milk and plasma in lactating women with plasma samples from non-lactating women. Venous blood samples were obtained from 17 healthy lactating women aged 22-35 years and from 16 age-matched controls. Colostrum, transitional and mature milk samples were collected just before suckling. The level of bioactive ghrelin was determined by RIA. Comparison of ghrelin values for lactating women showed significantly lower concentrations in colostrum (70.3 +/- 18 pg/ml), transitional milk (83.8 +/- 18pg/ml) and mature milk (97.3 +/- 13 pg/ml) than in the corresponding plasma samples (first day 95 +/- 16 pg/ml, 10th day 111 +/- 13 pg/ml and 15th day 135 +/- 16 pg/ml). The plasma concentrations were lower in the lactating than in the non-lactating women. Thus, the ghrelin levels in colostrum, transitional and mature milk were elavated concomitantly with increasing plasma ghrelin after delivery. The origin of milk ghrelin is not known, but it probably comes from the plasma.


Treatment of iron deficiency anemia in pediatric inflammatory bowel disease.
Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B12 and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.


Functional principles of baobab fruit pedicels - anatomy and biomechanics.
Fruit pedicels have to deal with increasing loads after pollination due to continuous growth of the fruits. Thus, they represent interesting tissues from a mechanical as well as a developmental point of view. However, only a few studies exist on fruit pedicels. In this study, we unravel the anatomy and structural-mechanical relationships of the pedicel of Adansonia digitata, reaching up to 90 cm in length. Morphological and anatomical analyses included examination of stained cross-sections from various positions along the stalk as well as X-ray microtomography and scanning electron microscopy. For mechanical testing, fibre bundles derived from the mature pedicels were examined via tension tests. For establishing the structural-mechanical relationships, the density of the fibre bundles as well as their cellulose microfibril distribution and chemical composition were analysed. While in the peduncle the vascular tissue and the fibres are arranged in a concentric ring-like way, this organization shifts to the polystelic structure of separate fibre bundles in the pedicel. The polystelic pedicel possesses five vascular strands that consist of strong bast fibre bundles. The fibre bundles have a Young's modulus of up to 5 GPa, a tensile strength of up to 400 MPa, a high density (>1 g cm-3) and a high microfibril angle of around 20°. The structural arrangement as well as the combination of high density and high microfibril angle of the bast fibre bundles are probably optimized for bearing considerable strain in torsion and bending while at the same time allowing for carrying high-tension loads.


Overall survival after reirradiation of spinal metastases - independent validation of predictive models.
It is unknown if survival prediction tools (SPTs) sufficiently predict survival in patients who undergo palliative reirradiation of spinal metastases. We therefore set out to clarify if SPTs can predict survival in this patient population. We retrospectively analyzed spinal reirradiations performed (n = 58, 52 patients, 44 included in analysis). SPTs for patients with spinal metastases were identified and compared to a general palliative score and to a dedicated SPT to estimate prognosis in palliative reirradiation independent of site (SPT-Nieder). Consistently in all tests, SPT-Nieder showed best predictive performance as compared to other tools. Items associated with survival were general condition (KPS), liver metastases, and steroid use. Other factors like primary tumor site, pleural effusion, and bone metastases were not correlated with survival. We adapted an own score to the data which performed comparable to SPT-Nieder but avoids the pleural effusion item. Both scores showed good performance in identifying long-term survivors with late recurrences. Survival prediction in case of spinal reirradiation is possible with sufficient predictive separation. Applying SPTs in case of reirradiation helps to identify patients with good life expectancy who might benefit from dose escalation or longer treatment courses.


A Nationwide Evaluation of Cardiothoracic Resident Research Productivity.
Evaluating the research productivity of cardiothoracic surgery residents during their training and early career is crucial for tracking their academic development. To this end, the training pathway of residents and the characteristics of their program in relation to their productivity were evaluated. Alumni lists from integrated 6-year thoracic surgery (I-6) and traditional thoracic surgery residency programs were collected. A Python script was used to search PubMed for publications and the iCite database for citations from each trainee. Publications during a 20-year time span were stratified by the year of publication in relation to the trainee's graduation from thoracic surgery residency. Trainees were analyzed by training program type, institutional availability of a cardiothoracic surgery T32 training grant, and protected academic development time. A total of 741 cardiothoracic surgery graduates (I-6, 70; traditional, 671) spanning 1971 to 2021 from 57 programs published >23,000 manuscripts. I-6 trainees published significantly more manuscripts during medical school and residency compared with traditional trainees. Trainees at institutions with cardiothoracic surgery T32 training grants published significantly more manuscripts than those at non-T32 institutions (13 vs 9; P = .0048). I-6 trainees published more manuscripts at programs with dedicated academic development time compared with trainees at programs without protected time (22 vs 9; P = .004). I-6 trainees publish significantly more manuscripts during medical school and residency compared with their traditional colleagues. Trainees at institutions with T32 training grants and dedicated academic development time publish a higher number of manuscripts than trainees without those opportunities.


An automated method for measuring lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma.
Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) play a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides. Quantification of LPL and HTGL activity is useful for diagnosing lipid disorders, but there has been no automated method for measuring these lipase activities. The automated kinetic colorimetric method was used for assaying LPL and HTGL activity in the post-heparin plasma using the natural long-chain fatty acid 2-diglyceride as a substrate. LPL activity was determined with apoCII and HTGL activity was determined without apoCII with 2 channel of auto-analyzer. The calibration curve for dilution tests of the LPL and HTGL activity assay ranged from 0.0 to 500 U/L. Within-run CV was obtained within a range of 5%. No interference was observed in the testing of specimens containing potentially interfering substances. The measurement range of LPL activity in the post-heparin plasma was 30-153 U/L, while HTGL activity was 135-431 U/L in normal controls. The L PL and HTGL activity assays are applicable to quantitating the LPL and HTGL activity in the post-heparin plasma. This assay is more convenient and faster than radiochemical assay and highly suitable for the detection of lipid disorders.


Seasonal abundance of Muscidae (Diptera) associated with cattle on a northern Transvaal farm.
Face flies were collected from cattle over a 14-mo period in an area where Parafilaria bovicola Tubangui was prevalent. Three species of Musca known to be vectors of P. bovicola were found. Two of the species (Musca lusoria Wiedeman and M. xanthomelas Wiedeman) were collected throughout the year, and M. nevilli Kleynhans was abundant only in autumn.


Metastatic spread from squamous cell carcinoma of the hypopharynx to the totally implantable venous access port insertion site: Case report and review of literature.
The totally implantable venous access port plays a crucial role in delivering chemotherapy in the outpatient setting. Here, we report the first case of a patient with hypopharyngeal tumor who developed chest wall metastasis over the totally implantable venous access port inserted in the internal jugular vein. Our patient, a 58-year-old man with a hypopharyngeal tumor presented with a lump over the totally implantable venous access port site. The port was removed and the lump was biopsied. The CT studies showed that the tumor had spread along the catheter from the hypopharynx to the chest wall. The pathology from the biopsy showed squamous cell carcinoma (SCC). The patient had poor performance status and opted for hospice care. We present a novel case of metastasis over the totally implantable venous access port implanted in a patient with a hypopharyngeal tumor. We also reviewed relevant literature comparing the data from percutaneous endoscopic gastrostomy (PEG) tube site metastasis with our patient and other similar case reports.


The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P.
Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4+ T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection.


Fast and flexible processing of large FRET image stacks using the FRET-IBRA toolkit.
Ratiometric time-lapse FRET analysis requires a robust and accurate processing pipeline to eliminate bias in intensity measurements on fluorescent images before further quantitative analysis can be conducted. This level of robustness can only be achieved by supplementing automated tools with built-in flexibility for manual ad-hoc adjustments. FRET-IBRA is a modular and fully parallelized configuration file-based tool written in Python. It simplifies the FRET processing pipeline to achieve accurate, registered, and unified ratio image stacks. The flexibility of this tool to handle discontinuous image frame sequences with tailored configuration parameters further streamlines the processing of outliers and time-varying effects in the original microscopy images. FRET-IBRA offers cluster-based channel background subtraction, photobleaching correction, and ratio image construction in an all-in-one solution without the need for multiple applications, image format conversions, and/or plug-ins. The package accepts a variety of input formats and outputs TIFF image stacks along with performance measures to detect both the quality and failure of the background subtraction algorithm on a per frame basis. Furthermore, FRET-IBRA outputs images with superior signal-to-noise ratio and accuracy in comparison to existing background subtraction solutions, whilst maintaining a fast runtime. We have used the FRET-IBRA package extensively to quantify the spatial distribution of calcium ions during pollen tube growth under mechanical constraints. Benchmarks against existing tools clearly demonstrate the need for FRET-IBRA in extracting reliable insights from FRET microscopy images of dynamic physiological processes at high spatial and temporal resolution. The source code for Linux and Mac operating systems is released under the BSD license and, along with installation instructions, test images, example configuration files, and a step-by-step tutorial, is freely available at github.com/gmunglani/fret-ibra.


ERF4 affects fruit firmness through TPL4 by reducing ethylene production.
The firmness of fleshy fruit crops has a significant effect on their quality, consumer preference, shelf life and transportability. In a combined quantitative trait locus and genome-wide association studies study of apple fruit texture, we identified a mutation (C-G) in the ethylene response factor-associated amphiphilic repression (EAR) motif in the coding region of the apple ETHYLENE RESPONSE FACTOR4 (ERF4) gene. Chromatin immunoprecipitation sequencing showed that ERF4 binds to the promoter of ERF3, which is involved in regulation of ethylene biosynthesis. The EAR mutation in ERF4 results in reduced repression of ERF3 expression, which is turn promotes ethylene production and loss of fruit firmness. ERF4 acts as a transcriptional repressor whose activity is modulated by a TOPLESS co-repressor 4 (TPL4)-binding EAR repression motif. Biolayer interferometry analysis showed that the mutation in the EAR motif causes a reduction in the interaction with TPL4. Suppression of ERF4 or TPL4 promoted fruit ripening and ethylene production. Taken together, our results provide insights into how ERF4 allelic variation underlies an important fruit quality trait.


[Efficacy and safety of vardenafil in men with erectile dysfunction in general clinical practice].
Since fixed-dose vardenafil clinical trails don't fully represent utilization of phosphodiesterase-5 (PDES) inhibitor in general clinical practice. This article reviews flexible-dose and community practice studies, to assess the efficacy and safety of vardenafil in general clinical practice. The results show that vardenafil improves erectile function in most men treated for ED in clinical practice, and well tolerated.


Educational interventions on evidence-based nursing in clinical practice: A systematic review with qualitative analysis.
To gather, assess and synthesise the currently available evidence of educational interventions on evidence-based nursing (EBN). Previous systematic reviews have focused on the items used in reporting educational interventions for facilitating evidence-based practices in medicine and health care or teaching research literacy in nursing as well as on the outcomes of these interventions. A systematic review based on a procedure of the Centre for Reviews and Disseminations for conducting a systematic review of health interventions. Texts from 2008 to 2015 were sought from the Cochrane, CINAHL and PubMed Medline databases. Eight studies were selected for the final data and reviewed for quality. Data were analysed with narrative synthesis including qualitative content analysis. Four main categories and sixteen subcategories were identified. The learning contents included principles of EBN and research, the process of EBN, and planning a change in practice. The most popular teaching/learning methods were lectures/didactic presentations and group work. The interventions encouraged learners to critically examine and evaluate their practice. The interventions also improved participants' capacity to identify the need for research evidence in clinical practice. The educational interventions were fairly similar and had promising results. However, as the level of evidence was modest in the studies, there are several development needs for interventions and further research challenges. Interventions should provide participants with sufficient competences for implementing every step of EBN, with special focus on the implementation of evidence in patient care. The assessment of the outcomes of interventions should cover all learning categories of EBN with focus on medium to long-term effectiveness. The influence of different teaching/learning methods and learning contexts and settings should be investigated further.


High-performance liquid chromatographic determination of Tornalate in solution dosage forms; a specificity study.
A reversed-phase high-performance liquid chromatographic method has been applied utilizing ion-pairing to measure Tornalate in solution dosage forms. Specificity of the method was demonstrated by selectivity for Tornalate analysis, analysis of stressed samples and by peak homogeneity tests. These included the diode-array derived spectral overlay test and fraction collection with rechromatography in an alternate normal phase system. Linearity was also demonstrated in terms of recovery from synthetic samples and detector response.


Host plants of Empria sawflies (Hymenoptera, Tenthredinidae) in Japan include Rhododendron (Ericaceae).
New host plant records are given for six Empria species from Japan. They are Rosa multiflora [Rosaceae] for E. honshuana Prous & Heidemaa, 2011, Rubus sp. [Rosaceae] for E. japonica Heidemaa & Prous, 2011, Geum japonicum and G. calthifolium var. nipponicum [Rosaceae] for E. loktini Ermolenko, 1971, Rosa multiflora, Potentilla indica and probably Rubus parvifolius [Rosaceae] for E. quadrimaculata Takeuchi, 1952, Rhododendron molle subsp. japonicum [Ericaceae] for E. takeuchii Prous & Heidemaa, 2011, and Geum japonicum and Filipendula camtschatica [Rosaceae] for E. tridentis Lee & Ryu, 1996. This is the first record of Ericaceae as a host plant of Empria. The mode of host shifts in the evolution of Empria is inferred by using a phylogenetic hypothesis proposed by Prous et al. (2011a).


Does customised care improve satisfaction and positively enable parents in sustained home visiting for mothers and children experiencing adversity?
The Maternal Early Childhood Sustained Home-visiting program (MECSH) is a structured nurse-delivered program designed to address health inequities experienced by families experiencing significant adversity. There is strong evidence for the effectiveness of this program, but limited research exploring the practice and process elements that are core to positive parent outcomes. This study aimed to examine the relationship between customised care related to the mother's risk factors and parent satisfaction and enablement in the delivery of a MECSH-based program. A cross-sectional study design was used. Program delivery data collected as part of a large randomised controlled trial of a MECSH-based sustained nurse home visiting program in Australia (right@home) were analysed. This study used the data collected from the intervention arm in the trial (n = 352 women). Parent satisfaction was measured at child age 24 months using the modified short-form Patient Satisfaction Questionnaire. Parent enablement was measured at child age 24 months by a modified Parent Enablement Index. Customised care was defined as appropriate provision of care content in response to four maternal risks: smoking, mental health, domestic violence and alcohol and drugs. Logistic analysis was performed to assess the impact of customised care on parent satisfaction and enablement while adjusting for covariates such as sociodemographic factors. A significance level of 95% was applied for analysis. Our results indicated high levels of satisfaction with the care provided and positive enablement. There were several sociodemographic factors associated with satisfaction and enablement, such as language spoken at home and employment experience. The mothers who received customised care in response to mental health risk and domestic violence had significantly greater satisfaction with the care provided and experienced an increase in enablement compared to those who did not receive such care. This study contributes to the existing body of empirical research that examines the relationship between care processes and client outcomes in the delivery of home visiting services. It is essential for the sustained nurse home visiting service model to be flexible enough to cater for variations according to family circumstances and needs while maintaining a core of evidence-based practice.


The canine external carotid vasoconstrictor 5-HT1 receptor: blockade by 5-HT1B (SB224289), but not by 5-HT1D (BRL15572) receptor antagonists.
In vagosympathectomised dogs pre-treated intravenously (i.v.) with mesulergine (300 microg/kg), 1-min intracarotid (i.c.) infusions of 5-hydroxytryptamine (5-HT; 0.3-30 microg/min) and sumatriptan (1-30 microg/min) dose-dependently decreased external carotid blood flow, without affecting mean blood pressure or heart rate. Treatment with the selective 5-HT1B receptor antagonist SB224289 (2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4'(5-methyl-1,2,4-oxadiazo l-3-yl) biphenyl-4-carbonyl]furo[2,3f]indole-3-spiro-4'-piperidine hydrochloride; 30-300 microg/kg, i.v.) produced a potent, specific and dose-dependent blockade of this response, whereas the selective 5-HT1D receptor antagonist BRL15572 (1-(3-chlorophenyl)-4-[3,3-diphenyl(2-(S,R) hydroxypropanyl)piperazine]hydrochloride; 30-300 microg/kg, i.v.) was ineffective. It is concluded that mainly 5-HT1B, but not 5-HT1D receptors mediate the canine external carotid vasoconstriction by 5-HT and sumatriptan.


A review of office urethroscopy and cystometry.
The authors review the indications and findings of urethroscopic and cystometric examinations carried out on 279 patients. The most common indication was urinary incontinence, stress and urge types. Other indications included dysuria, recurrent urinary infections, and preoperative indications. The most common finding was chronic urethritis. Other findings included urethral stenosis, unstable bladder, anatomic stress incontinence, and urethral diverticulum. Changes in the vesical neck, characteristic of anatomic stress incontinence, were found in 43% of patients who complained of stress incontinence. This resulted in fewer patients being treated operatively. Chronic urethritis was present in 48% of patients with urinary incontinence. Many patients became continent after medical treatment for chronic urethritis. Office urethroscopy and cystometry are invaluable to properly select patients for operative treatment of stress incontinence. Chronic urethritis often will be found to be the source of many pelvic complaints.


Limbal Stem Cell Dysfunction Induced by Severe Dry Eye via Activation of the p38 MAPK Signaling Pathway.
Severe dry eye (SDE) can cause grievous damage to the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, the current study established an SDE rat model by removing the extraorbital and infraorbital lacrimal glands and maintaining them in a low-humidity environment. One month after the surgery, aqueous tear secretion was reduced dramatically, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expressions of keratin 12 and paired box gene 6 were down-regulated dramatically, while those of keratin 10, small proline-rich protein 1b, and mucin 5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker adenosine 5'-triphosphate-binding cassette member 2 and the limbal epithelial colony-forming efficiency were decreased in the SDE condition. Furthermore, the p38 mitogen-activated protein kinase signaling pathway was activated in the limbal corneal epithelium of SDE rats. The abnormal differentiation and stemness loss in the corneal epithelium could be reversed upon treatment with a p38 inhibitor in a SDE in vivo model and in vitro hyperosmolar corneal epithelial culture conditions. These data suggest that SDE can lead to limbal stem cell dysfunction, and p38 mitogen-activated protein kinase signaling pathway activation plays an essential role in this process.


Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits.
A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.


Topical and systemic medications for the treatment of primary Sjögren's syndrome.
The treatment of primary Sjögren's syndrome (SS) is based principally on the management of sicca features and systemic manifestations. Sicca manifestations are treated symptomatically through administration of topical therapies, such as saliva substitutes and artificial tears; in patients with residual salivary gland function, stimulation of salivary flow with a sialogogue is the therapy of choice. The management of extraglandular features must be tailored to the specific organ or organs involved; however, limited data have been obtained from controlled trials in SS to guide the treatment of systemic symptoms using therapies including antimalarials, glucocorticoids, immunosuppressive drugs and biologic agents. Nevertheless, randomised controlled trials of biologic agents that target molecules and receptors involved in the aetiopathogenesis of primary SS have initiated a new era in the therapeutic management of the disease, although the potential risks and benefits of these agents must be carefully considered. In this Review, we analyse the evidence regarding the efficacy of the therapeutic agents currently available to treat the manifestations of SS. On the basis of this evidence, we provide guidance on the use of these agents in different clinical scenarios.


The Naked Mole-Rat as a Model for Healthy Aging.
Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality with age, maintain several physiological functions until nearly the end of their lifetime, and rarely develop cancer and Alzheimer's disease. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These unique characteristics of NMRs have attracted considerable interest from zoological and biomedical researchers. This review summarizes previous studies of the ecology, hypoxia tolerance, longevity/delayed aging, and cancer resistance of NMRs and discusses possible mechanisms contributing to their healthy aging. In addition, we discuss current issues and future perspectives to fully elucidate the mechanisms underlying delayed aging and resistance to age-related diseases in NMRs.


Variability of the QTc interval: impact on defining drug effect and low-frequency cardiac event.
Prolongation of the QT interval corrected for heart rate (QTc) can lead to the development of torsades de pointes, a life-threatening form of polymorphic ventricular tachycardia. However, the QTc interval duration exhibits a high degree of spontaneous variability and is not necessarily a direct predictor of the risk of torsades. This observation holds implications for the assessment of the potential proarrhythmic effects of noncardiac pharmacologic agents. To date, the antihistamine terfenadine is the only noncardiac drug that has undergone a comprehensive and systematic evaluation related to the consequences of its causing QTc prolongation. The results suggest that QTc prolongation resulting solely from terfenadine at clinical doses does not have an important impact on clinically relevant endpoints. The risk of serious ventricular arrhythmias with terfenadine using epidemiologic data is the same or less than that associated with traditional first-generation antihistamines. The risk of a clinical cardiac event (QTc prolongation, ventricular arrhythmias, syncope, or sudden death) with terfenadine is similar to that of other antihistamines. Factors associated with increased risk in patients taking terfenadine include significant liver disease, hypokalemia, overdose, and concomitant administration of ketoconazole-like agents or erythromycin; use of terfenadine is relatively contraindicated in these settings. No increased risk of serious arrhythmias has been confirmed in conjunction with the use of terfenadine in patients with cardiac disease.