Developing, implementing, and monitoring tailored strategies for integrated knowledge translation in five sub-Saharan African countries.
Integrated knowledge translation (IKT) through strategic, continuous engagement with decision-makers represents an approach to bridge research, policy and practice. The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA +), comprising research institutions in Ethiopia, Malawi, Rwanda, South Africa, Uganda and Germany, developed and implemented tailored IKT strategies as part of its multifaceted research on prevention and care of non-communicable diseases and road traffic injuries. The objective of this article is to describe the CEBHA + IKT approach and report on the development, implementation and monitoring of site-specific IKT strategies. We draw on findings derived from the mixed method IKT evaluation (conducted in 2020-2021), and undertook document analyses and a reflective survey among IKT implementers. Quantitative data were analysed descriptively and qualitative data were analysed using content analysis. The authors used the TIDieR checklist to report results in a structured manner. Preliminary IKT evaluation data (33 interviews with researchers and stakeholders from policy and practice, and 31 survey responses), 49 documents, and eight responses to the reflective survey informed this article. In each of the five African CEBHA + countries, a site-specific IKT strategy guided IKT implementation, tailored to the respective national context, engagement aims, research tasks, and individuals involved. IKT implementers undertook a variety of IKT activities at varying levels of engagement that targeted a broad range of decision-makers and other stakeholders, particularly during project planning, data interpretation, and output dissemination. Throughout the project, the IKT teams continued to tailor IKT strategies informally and modified the IKT approach by responding to ad hoc engagements and involving non-governmental organisations, universities, and communities. Challenges to using systematic, formalised IKT strategies arose in particular with respect to the demand on time and resources, leading to the modification of monitoring processes. Tailoring of the CEBHA + IKT approach led to the inclusion of some atypical IKT partners and to greater responsiveness to unexpected opportunities for decision-maker engagement. Benefits of using systematic IKT strategies included clarity on engagement aims, balancing of existing and new strategic partnerships, and an enhanced understanding of research context, including site-specific structures for evidence-informed decision-making.


[Epidemiological investigation of two leptospirosis death cases in Guizhou Province].
Objective: To conduct an epidemiological investigation of two leptospirosis death cases reported in Guizhou Province in 2014. Methods: The information of the patients were investigated and analyzed. The serological detection, samples of the two patients was detected using ELISA and microscopic agglutination test (MAT). Leptospira carrier status of murine host animal in the living environment of the two patients was investigated in October and November of 2014. Leptospires in the kidney were cultured and isolated, the isolates were identified using Leptospira specific PCR and further identified with serogroup specific PCR and the conventional MAT. The relativity between the carrier status of murine and the death cases of human leptospirosis was analyzed. Results: The two death cases of human leptospirosis came from Liping County and the clinical symptoms were consistent with the diagnosis criteria for Leptospirosis. The results of ELISA detection showed that the anti-Leptospira antibody was positive for one of the death cases, MAT identified the serum reacted with sera-group icterohaemorrhagiae Leptospira, while the serum sample of the other case was failed to perform antibody detection due to hemolysis. 1 600 traps were placed in the living environment of the two death cases and 183 murine rodents were trapped. The murine density was 11.44% (183/1 600); 40 leptospirea suspected strains were isolated and all of them were isolated from Apodemus agrarius. The positive rate was 21.86% (40/183); 95 Apodemus agrarius were trapped and the murine density was 5.93% (95/1 600). Species specific PCR identified all the 40 strains as Leptospire. Serogroup specific PCR further identification showed that they were iterohaemorrahgiae serogroup Leptospria. interrogans. Conclusion: Anti-iterohaemorrahgiae Leptospira antibody was detected from one of the two patients. 40 strains of iterohaemorrahgiae serogroup Leptospira interrogans were isolated and all of them were isolated from Apodemus agrarius in the living environment and the serogroup of the Leptospira matched with the serological detection results from patients, which indicated that the two death cases were caused by the infection of iterohaemorrahgiae serogroup Leptospira interrogans, and Apodemus agrarius were the potential source of infection.


[Randomized double-blind study of the analgesic effect of caerulein and morphine in chronic tumor pain].
Caerulein (CRL) (5 micrograms i.m.) and morphine (10 mg i.m.) have been tested for their analgesic activity in a double blind randomized study in a total of 36 patients with medium to severe tumor pains. A decrease of more than 20 mm on a visual analogue scale (VAS) was taken as a criterion for successful therapy. This was the case in 67% of the patients treated with morphine and 50% of those treated with CRL. This difference is statistically not significant, but CRL has significantly fewer side-effects than morphine. The present data do not permit a definitive judgement on the value of CRL in the treatment of tumor pains. Further studies with more patients and different doses and administration routes are warranted.


Enzyme-catalyzed reactions of the carcinogen N-hydroxy-2-fluorenylacetamide with nucleic acid.
A protein fraction obtained by gel filtration of a 105,000g supernatant of rat liver catalyzes three reactions of the hepatocarcinogen N-hydroxy-2-fluorenylacetamide with nucleic acid. Cofactor requirements and isotopic studies suggest that the reactive intermediates involved may be N-2-fluorenylhydroxylamine, and phosphate and sulfate esters of N-hydroxy-2-fluorenylacetamide.


Inter-relationship between electrophoretic characteristics of pseudocereal and cereal proteins and their microscopic structure for possible substitution based on nutritional evaluation.
Amaranth, soybean and maize were screened for proteins and their nutritional value. Isopropanol-soluble protein and buffer-soluble protein fractions were extracted from seeds and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The comparison of the identity and differences between investigated plants was carried out by the obtained SDS-PAGE electrophoretic patterns, and their microstructure was determined by scanning electron microscopy. Electrophoretic patterns of extracted proteins have shown that the main protein subunits were concentrated between 10 and 50 kDa. Variations were found in major fractions and minor bands as well as in the fine structure. The microstructure of pseudocereal and cereal protein fractions was inter-related with the results obtained by their electrophoretic separation. Pseudocereal amaranth can be used as a nutritive substitute of cereal maize in functional foods.


Methacholine bronchial challenge using a dosimeter with controlled tidal breathing.
A new inhalation synchronised dosimeter triggered by low inspiratory flow rates has been assessed. The methacholine challenge test using dosimeter nebulisation with controlled tidal breathing was compared with continuous nebulisation using De Vilbiss No 40 nebulisers with deep inhalations in 11 asthmatic subjects. Within subject PD20 FEV1 values were lower with the dosimeter method than with the continuous nebulisation method (geometric means 158 and 588 micrograms). The repeatability of the dosimeter method with controlled tidal breathing was studied in 11 asthmatic subjects, and the 95% range for a single measurement was +/- 0.72 doubling doses of methacholine. The dosimeter method has greater efficacy because aerosol is delivered during the first part of an inhalation, minimising loss of aerosol outside the respiratory tract. The dosimeter technique combined with controlled tidal breathing appears to be a useful method for carrying out standardised non-specific bronchoprovocation tests.


Detection, characterization and identification of major constituents in Zhimu-Baihe herb-pair extract by fast high-performance liquid chromatography and time-of-flight mass spectrometry through dynamic adjustment of fragmentor voltage.
This work describes a novel methodology for unequivocal identification of chemical constituents in Zhimu-Baihe herb-pair (ZMBHHP). Compounds were removed from ZMBHHP by ultrasonic extraction with 70% ethanol, and then analyzed by fast high-performance liquid chromatography (HPLC) coupled with time-of-flight mass spectrometry (TOFMS). The accurate-mass capability of the TOF analyzer allowed reliable confirmation of the identity of the detected compounds, normally with mass errors below 3 ppm in routine analysis. This mass accuracy was sufficient to verify the elemental compositions of the chemical constituents in ZMBHHP. With dynamic adjustment of fragmentor voltage in TOFMS, an efficient ion transmission was achieved to obtain the best sensitivity and abundant fragmentation. By accurate mass measurements for each molecular ion and subsequent fragment ions, a reliable identification and differentiation of 24 saponins, 3 xanthones, 1 anthraquinone and 2 alkaloids was described here, including four groups of isomers. It is concluded that this fast and sensitive HPLC/ESI-TOFMS technique is powerful in qualitative analysis of complex herbal medicines in terms of sensitivity, selectivity, resolving power, time savings and lower solvent consumption. Furthermore, the data gathered in this study may be helpful for understanding the synergistic nature of this herb pair in traditional Chinese medicine (TCM) and further pharmacokinetic studies of ZMBHHP.


Effects of Spectral Envelope and Fundamental Frequency Shifts on the Perception of Foreign-Accented Speech.
To investigate the role of spectral pattern information in the perception of foreign-accented speech, we measured the effects of spectral shifts on judgments of talker discrimination, perceived naturalness, and intelligibility when listening to Mandarin-accented English and native-accented English sentences. In separate conditions, the spectral envelope and fundamental frequency (F0) contours were shifted up or down in three steps using coordinated scale factors (multiples of 8% and 30%, respectively). Experiment 1 showed that listeners perceive spectrally shifted sentences as coming from a different talker for both native-accented and foreign-accented speech. Experiment 2 demonstrated that downward shifts applied to male talkers and the largest upward shifts applied to all talkers reduced the perceived naturalness, regardless of accent. Overall, listeners rated foreign-accented speech as sounding less natural even for unshifted speech. In Experiment 3, introducing spectral shifts further lowered the intelligibility of foreign-accented speech. When speech from the same foreign-accented talker was shifted to simulate five different talkers, increased exposure failed to produce an improvement in intelligibility scores, similar to the pattern observed when listeners actually heard five foreign-accented talkers. Intelligibility of spectrally shifted native-accented speech was near ceiling performance initially, and no further improvement or decrement was observed. These experiments suggest a mechanism that utilizes spectral envelope and F0 cues in a talker-dependent manner to support the perception of foreign-accented speech.


Correlation between left ventriculography, auscultation, and M-mode and two-dimensional echocardiography in mitral valve prolapse.
Mitral valve prolapse (MVP) is a common valvular abnormality which is observed in as many as 5% of the general population. Although invasive as well as noninvasive tools have been developed to determine the existence of this disorder, none is perfect and false negative as well as false positive diagnoses abound. Because MVP is a relatively benign disorder, it has also not been easy to make the usual clinical-pathological correlations. Left ventriculography is considered by many to be the gold standard, but this designation is probably not deserved. The angiographic criteria used by most do not permit unequivocal separation of normal mitral valve systolic bulging from pathologic MVP, and the interobserver and intraobserver variability of interpretation is high. However, false positive diagnoses can be eliminated if MVP is diagnosed only when para-annular displacement of mitral leaflet tissue is detected during systole rather than simple leaflet bulging. Although mid-systolic clicks and late systolic murmurs have proven to be the auscultatory hallmarks of this disorder, many patients have these signs without other diagnostic findings, consequently making it impossible to confirm the presence of MVP. Furthermore, the appearance of diagnostic echocardiographic abnormalities in patients with normal cardiac examinations implies that auscultation is not a sensitive marker of MVP. Both M-mode and two-dimensional echocardiography have technical limitations and the repeatability of interpretation of these tests is disappointingly low (80 to 90%). Because of these difficulties the angiographic-echocardiographic correlation is only fair. Nonetheless echocardiography has generally been accepted as the diagnostic modality of choice. Future technical improvements will likely enhance the diagnostic accuracy of this technique.


The ultimate diagnoses of patients undergoing temporal artery biopsies.
Patients with signs and symptoms of giant cell arteritis may have normal temporal artery biopsy specimens. To study the relationships between signs and symptoms of this disease and the ultimate clinical diagnosis, we reviewed 51 patients who had undergone temporal artery biopsy. The mean age of the patients with abnormal biopsy specimens was higher than that of patients with normal biopsy specimens. We found headache, fever, and jaw claudication were useful symptoms in predicting abnormal biopsy specimens. The ultimate diagnoses of patients with normal biopsy specimens and no response to treatment showed high incidence of malignant neoplasms and diabetes mellitus.


Time-resolved near-edge x-ray absorption fine structure spectroscopy on photo-induced phase transitions using a tabletop soft-x-ray spectrometer.
We present a table-top soft-x-ray spectrometer for the wavelength range λ = 1-5 nm based on a stable laser-driven x-ray source, making use of a gas-puff target. With this setup, optical light-pump/soft-x-ray probe near-edge x-ray absorption fine structure (NEXAFS) experiments with a temporal resolution of about 230 ps are feasible. Pump-probe NEXAFS measurements were carried out in the "water-window" region (2.28 nm-4.36 nm) on the manganite Pr(0.7)Ca(0.3)MnO(3), investigating diminutive changes of the oxygen K edge that derive from an optically induced phase transition. The results show the practicability of the table-top soft-x-ray spectrometer on demanding investigations so far exclusively conducted at synchrotron radiation sources.


[Drug therapy in peripheral arterial occlusive disease].
Drugs used for improvement or stabilization of peripheral circulation include antiaggregants or anticoagulants for secondary prevention of arteriosclerosis, vasoactive substances and fibrinolytic agents. -Two prospective trials document that aspirin or the combination of aspirin and dipyridamole reduce progression of arterial occlusive disease significantly in comparison to placebo. Aspirin is best suited for secondary prevention of recurrent stenoses or occlusions after carotid or femoral endarterectomy, whereas anticoagulants are preferred in patients with embolism and after peripheral implantation of venous bypasses. -Significant improvement of walking distance is achieved by several compounds influencing blood rheology. The effect does not exceed that obtained by physical training. If reconstructive arterial surgery or percutaneous transluminal angioplasty are not possible, some patients with rest pain or gangrene may be successfully treated by intraarterial administration of prostaglandin E1.


Prasugrel use in a patient allergic to clopidogrel: effect of a drug shortage on selection of dual antiplatelet therapy.
A case illustrating multiple considerations in choosing safe and effective dual antiplatelet therapy for a patient with a history of clopidogrel allergy-including concerns relating to a national drug shortage-is described. A 75-year-old woman required dual antiplatelet therapy (aspirin plus a thienopyridine) after a cardiac catheterization procedure; during a prior emergency department visit for acute coronary syndrome, she had experienced an allergic reaction within 24 hours of receiving dual therapy including clopidogrel. A team of pharmacy and allergy staff determined that challenging the patient with prasugrel was the best treatment option. Key considerations in the decision-making process included (1) concerns that an alternative thienopyridine, ticlopidine, might be unavailable for long-term outpatient use due to an ongoing national drug shortage, (2) the patient's concomitant use of metoprolol (cessation of β-blocker use is recommended for four days before attempted clopidogrel desensitization), and (3) recent reports of the safe use of prasugrel in three patients with a history of clopidogrel allergy. In the case described here, prasugrel administration was effective and did not result in adverse effects; however, the risk of cross-reactivity of clopidogrel and ticlopidine or prasugrel remains largely unknown. The case highlights the importance of careful consideration of a number of patient- and drug-specific factors in the selection of the most appropriate antiplatelet dual therapy for patients with a history of allergic reactions to clopidogrel. A shortage of ticlopidine prompted the use of prasugrel in a clopidogrel-allergic patient requiring dual antiplatelet therapy. Prasugrel therapy was well tolerated, with no evidence of allergic reaction.


Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver transplantation.
A meta-analysis was carried out of published studies on the effect of the CYP3A5 6986A>G polymorphism in liver donors and transplant recipients on tacrolimus pharmacokinetics. Cohort studies that evaluated the relationship between the CYP3A5 polymorphism in liver donors and transplant recipients and tacrolimus, trough blood concentration normalized for the daily dose (C) per kilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to 1 year after transplantation, were included. Data were not restricted by patient age or the language or journal of publication. A literature search was conducted using the Cochrane Library, MEDLINE, EMBASE, and grey literature, and articles published up to 24 April 2013 were selected. Data were pooled (random-effects model), and the results were expressed as the mean difference of the corresponding C/D ratios and 95% confidence intervals. Six studies involving donor genotypes (254 patients) and four involving recipient genotypes (180 patients) were ultimately included. The meta-analysis showed the C/D ratio to be significantly higher in recipients with nonexpresser donor variants at all time points. In recipients, the variant did not influence the C/D ratio. The presence of the CYP3A5 6986A>G polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although only the evidence available for the first month after transplantation was of adequate quality for demonstrating a significant difference. The evidence provided here shows no effect of the recipient genotype; however, the quality of the evidence was low, thereby precluding the drawing of firm conclusions.


[Major neurological complications following liver transplantation and their management].
To study the clinical features, underlying mechanism and management of major neurological complications following liver transplantation. The data of 467 patients undergoing liver transplantation from Oct. 2003 to Sep. 2005 were retrospectively reviewed. Neurological complications occurred in 91 (19.49%) cases. The most common neurological complications were encephalopathy (72 cases), followed by stroke (12 cases), seizure (4 cases), central pontine myelinolysis (3 cases), and central nervous system infections (2 cases). Five encephalopathy cases were treated with continuous renal replacement and 5 intracranial hemorrhage cases with neurosurgical intervention. The mortality related to neurological complications was 10.98% (12/91). Neurological complications are common and potentially fatal following liver transplantation involving several factors. CsA and FK506 may play an important role in the onset of neurological complications, and stroke, especially intracranial hemorrhage, has a high mortality. Combined therapies and timely modulation of the immunosuppressive regimens may improve the patient's outcome.


Self-Deception, Delusion and the Boundaries of Folk Psychology.
To what extent do self-deception and delusion overlap? In this paper we argue that both self-deception and delusions can be understood in folk-psychological terms. "Motivated" delusions, just like self-deception, can be described as beliefs driven by personal interests. If self-deception can be understood folk-psychologically because of its motivational component, so can motivated delusions. Non-motivated delusions also fit (to a large extent) the folk-psychological notion of belief, since they can be described as hypotheses one endorses when attempting to make sense of unusual and powerful experiences. We suggest that there is continuity between the epistemic irrationality manifested in self-deception and in delusion.


A link between occupant and vehicle accelerations during common driving tasks.
When evaluating occupant motions during driving tasks, it is desirable to have a well-established correlation between vehicle and occupant accelerations. Therefore, this study demonstrated a methodology to quantify accelerations experienced by the driver of a passenger vehicle and compare them to associated vehicle motions. Acceleration levels were measured at the seat and the driver's head, cervical spine, and lumbar spine during six non-collision driving tasks. Tasks included mounting a 127 mm (5 in) -high curb, crossing railroad tracks, driving on a rough road, braking heavily from 13.4 m/s (30 mph), having a 89 mm (3.5 in)-diameter roller sequentially pass under two tires, and dropping one tire from a 171-mm (6.75 in) height. The driver experienced peak resultant accelerations of similar magnitudes across all trials. Peak body accelerations were less than 1.2 g, including 0.82 g lumbar acceleration during heavy braking and 0.88 g head acceleration during the curb mount. These preliminary measurements are comparable to or lower than accelerations experienced during non-driving activities such as sitting quickly. This study contributes to the scientific understanding of accelerations experienced by vehicle occupants and demonstrates the potential to relate vehicle and occupant accelerations during common driving activities that do not involve collisions.


Neprilysin deficiency protects against fat-induced insulin secretory dysfunction by maintaining calcium influx.
Neprilysin contributes to free fatty acid (FFA)-induced cellular dysfunction in nonislet tissues in type 2 diabetes. Here, we show for the first time that with prolonged FFA exposure, islet neprilysin is upregulated and this is associated with reduced insulin pre-mRNA and ATP levels, oxidative/nitrative stress, impaired potassium and calcium channel activities, and decreased glucose-stimulated insulin secretion (GSIS). Genetic ablation of neprilysin specifically protects against FFA-induced impairment of calcium influx and GSIS in vitro and in vivo but does not ameliorate other FFA-induced defects. Importantly, adenoviral overexpression of neprilysin in islets cultured without FFA reproduces the defects in both calcium influx and GSIS, suggesting that upregulation of neprilysin per se mediates insulin secretory dysfunction and that the mechanism for protection conferred by neprilysin deletion involves prevention of reduced calcium influx. Our findings highlight the critical nature of calcium signaling for normal insulin secretion and suggest that interventions to inhibit neprilysin may improve β-cell function in obese humans with type 2 diabetes.


Ultrasonography and CT of the vas deferens in a neutered male dog with chronic exogenous estrogen exposure.
A 2-year-old male neutered Rat Terrier was presented for alopecia, recurrent urinary tract infections, and urinary incontinence. Abdominal ultrasound and CT identified a thin, tubular, paired structure arising from the craniodorsal aspect of an enlarged, cystic prostate. An atypical uterus masculinus was initially suspected, however it was then identified that the patient had chronic exogenous estrogen exposure, and surgical resection and histopathology was consistent with an enlarged and inflamed vas deferens. Vas deferens enlargement and vasitis secondary to chronic hyperestrogenism should be considered for a tubular, paired structure arising from the craniodorsal prostate in a male dog.


Case report of 2 sudden deaths after surgery for bone fracture: Usefulness of immunohistochemical analysis of coronary artery for identifying acute myocardial infarction.
Death following orthopedic surgery has become rare, but does occur. Acute myocardial infarction (AMI) can be a cause of such death, but diagnosis of AMI is often challenging, even by autopsy. We have recently experienced 2 cases of sudden death after bone fracture surgery, in which AMI and pulmonary thromboembolism were clinically suspected as causes of death. Case 1 was a 60-year-old male with a history of diabetes mellitus who died 7 days after surgery for Lisfranc dislocation fracture. Case 2 was a 75-year-old female who died several hours after surgery for proximal femur fracture. At autopsy, slight myocardial change suggestive of AMI, severe coronary stenosis, and pulmonary congestion were noted in case 1. No signs for AMI were observed, but diffuse fat emboli were identified in the pulmonary vasculature in Case 2. Thus, postmortem pathological diagnosis was AMI in case 1 and it was suggestive of fat emboli in case 2. Immunohistochemical analysis of smooth muscle markers in the coronary artery was performed in both cases. The positivity ratio of h-caldesmon to α-smooth muscle actin indicative of maturity of neointimal smooth muscle cells was preserved in case 2 but diminished in case 1, where coronary occlusion may have been caused via plaque rupture. Immunostaining of smooth muscle markers in the coronary artery may serve as a supporting tool in establishing or disregarding AMI at autopsy.


[On the evaluation of hospital care of persons of elderly and senile age].
The study was carried out in 2012-2014 on the of the hospital of veterans "The Republican medical center" with purpose of optimizing hospital care of population of elderly and senile age. The special record of hospitalized patient containing 16 questions was developed for sampling primary data. On the basis of received results the directions of development of hospital care to patients of elderly and senile age were determined.


A prospective study of patients' pain intensity after cardiac surgery and a qualitative review: effects of examiners' gender on patient reporting.
Background and aims As indicated by experimental studies, reports of pain intensity may depend on the examiner's gender. Until now, it is unclear whether this is relevant in clinical routine. This study investigated prospectively whether the gender of assessor plays a role in patients' pain reports and whether this role differs in male and female patients. Methods 165 patients (66.4 years±0.63; 118 males) scheduled for heart surgery were allocated consecutively to one examiner out of four students of both genders: two females and two males (aged 24.3 years±1.7). Therefore, the following study groups were defined: Group 1: female assessors-female patients, 2: female-male; 3: male-female, 4: male-male. Using a standardized analgesic scheme, patients were asked to rank their pain intensity on a numeric rating scale (NRS: 0-10), postoperatively. Statistics: Kruskal-Wallis, Mann-Whitney; p<0.05. Additionally, a qualitative literature review of the databases Medline and CENTRAL was performed focusing on experimental and clinical studies on experimenter gender bias. Due to the review, this prospective clinical study was designed to investigate whether patients after surgery report lower pain intensities when assessed by a female compared to a male assessor. Results Summarizing all patients, pain intensity on POD_1 was rated 4.0±2.4 on NRS and decreased on POD_2 to 3.0±2.1 [H(3)=37.941, p=0.000]. On average, pain intensity did not differ between males and females (NRS: 3.5 vs. 3.6). Only on the second postoperative day, more intense pain was reported in front of female assessors and less intense pain in front of male assessors (NRS: 3.4 vs. 2.4; p=0.000). A main effect for the four groups was seen (p=0.003): male patients reported higher pain scores to female assessors (NRS: 3.5 vs. 2.3; p=0.000). Conclusions Together, contrary to the expectations, patients after cardiac surgery reported a higher pain intensity in front of a female and a lower pain intensity in front of a male assessor. In particular, female caregivers may heighten the reported pain intensity up to 1.2 NRS-points; this bias seems to be more relevant for male patients. Implications Therefore, despite some methodological weakness, our data suggest that attention should be paid to a rather small, but somehow significant and consistent examiner gender bias after cardiac surgery especially in male patients. Further clinical studies are needed to show the true extent of clinical relevance and exact mechanisms underlying these gender reporting bias.


Two truncating USH3A mutations, including one novel, in a German family with Usher syndrome.
To identify the genetic defect in a German family with Usher syndrome (USH) and linkage to the USH3A locus. DNA samples of five family members (both parents and the three patients) were genotyped with polymorphic microsatellite markers specific for eight USH genes. Three affected family members underwent detailed ocular and audiologic characterization. Symptoms in the patients were compatible with Usher syndrome and show intrafamilial variation, for both hearing loss (ranging from severe to profound with non-linear progression) and vision. Genotyping of microsatellite markers for the different USH loci was in line with a defect in the USH3A gene on chromosome 3q25. Sequence analysis of the USH3A gene revealed two truncating mutations; c.149_152delCAGGinsTGTCCAAT, which has been described previously, and a novel mutation, c.502_503insA, segregating with the phenotype. To date, only 11 USH3A mutations have been described. This is the first description of a German family with USH due to USH3A mutations, including one novel. Our findings indicate that also in the Central European population, USH3A mutations should be considered in cases of USH.


Synthesis and Characterization of New Antibacterial Fluoride-Releasing Monomer and Dental Composite.
A new dimethacrylate chelating monomer containing a BisGMA-like backbone structure and a bis(carboxymethyl)-L-lysine chelating group and its ternary zirconium-fluoride complex (antibacterial fluoride-releasing monomer) have been synthesized. The monomer structures were confirmed by (1)H-NMR, (13)C-NMR, and ES-MS analysis. Several experimental fluoride-releasing dental composites containing different quantities of the new antibacterial fluoride-releasing monomer were formulated and tested for fluoride release, fluoride recharge, compressive and flexural strengths, water sorption and solubility. These composites displayed high fluoride release and recharge capabilities, as well as good physical and mechanical properties.


Evolution and functional characterization of the RH50 gene from the ammonia-oxidizing bacterium Nitrosomonas europaea.
The family of ammonia and ammonium channel proteins comprises the Amt proteins, which are present in all three domains of life with the notable exception of vertebrates, and the homologous Rh proteins (Rh50 and Rh30) that have been described thus far only in eukaryotes. The existence of an RH50 gene in bacteria was first revealed by the genome sequencing of the ammonia-oxidizing bacterium Nitrosomonas europaea. Here we have used a phylogenetic approach to study the evolution of the N. europaea RH50 gene, and we show that this gene, probably as a component of an integron cassette, has been transferred to the N. europaea genome by horizontal gene transfer. In addition, by functionally characterizing the Rh50(Ne) protein and the corresponding knockout mutant, we determined that NeRh50 can mediate ammonium uptake. The RH50(Ne) gene may thus have replaced functionally the AMT gene, which is missing in the genome of N. europaea and may be regarded as a case of nonorthologous gene displacement.


Migrating to the Modern PACS: Challenges and Opportunities.
With progressive advancements in picture archiving and communication system (PACS) technology, radiology practices frequently look toward system upgrades and replacements to further improve efficiency and capabilities. The transition between PACS has the potential to derail the operations of a radiology department. Careful planning and attention to detail from radiology informatics leaders are imperative to ensure a smooth transition. This article is a review of the architecture of a modern PACS, highlighting areas of recent innovation. Key considerations for planning a PACS migration and important issues to consider in data migration, change management, and business continuity are discussed. Beyond the technical aspects of a PACS migration, the human factors to consider when managing the cultural change that accompanies a new informatics tool and the keys to success when managing technical failures are explored. Online supplemental material is available for this article. ©RSNA, 2018.


Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care.
An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care.


Risk assessment of d-limonene: an example of male rat-specific renal tumorigens.
The naturally occurring food constituent d-limonene has been found to cause tumors at high doses only in the kidney of the male rat in association with the development of hyaline droplet nephropathy. In contrast, neither kidney tumors nor the associated nephropathy have been found in female rats or mice at much higher doses. Adult male rats produce large quantities of a specific low-molecular-weight protein in the liver, which is known as alpha 2U-globulin (alpha 2U-g). With administration of sufficient doses of d-limonene to male rats, this protein has been found to accumulate excessively in the P2 segment cells of renal proximal tubules, resulting in hyaline droplet formation as a manifestation of protein overload. Hyaline droplet accumulation is the first stage in a unique sequence of nephropathic lesions (also known as alpha 2U-g nephropathy), including granular casts in the outer medulla and linear mineralization in the papilla. The mechanism underlying protein accumulation appears to be the reversible binding of chemical to alpha 2U-g with subsequent prolongation of its half-life in the tubule cell. In the case of d-limonene, the minor metabolite d-limonene-1,2-oxide has been shown to be the primary chemical species that binds reversibly to alpha 2U-g, impeding the normal process of lysosomal proteinase degradation of alpha 2U-g. The ensuing nephropathy is associated with a sustained increase in compensatory renal tubule cell proliferation, which provides the putative mechanistic link with renal tumor formation possibly through tumor promotion of spontaneously initiated cells or enhanced spontaneous mutagenesis. This proposed mechanism has been supported by additional information, including negative genotoxicity tests for d-limonene and its oxide metabolites, experimentally verified tumor promotion, and enhanced cell proliferation primarily in P2 segment tubule cells in male F344 rats, but no such effects in the alpha 2U-g-deficient NBR rat. The mechanism of d-limonene tumor development does not appear to be possible in humans since neither the quantity nor the type of protein that binds d-limonene or d-limonene-1,2-oxide is present. The deduction that the renal tumors induced in male rats are not relevant to human carcinogenicity in the hazard evaluation step of risk assessment completes the evaluation of human risk for d-limonene. Consequently, it can be concluded that d-limonene does not pose any carcinogenic or nephrotoxic risk to humans.(ABSTRACT TRUNCATED AT 400 WORDS)


Health Care Systems and Transitions of Care: Implication on Interdisciplinary Pharmacy Services.
Effective medication management is critical to successful patient outcomes. Pharmacists and pharmacy technicians working within North Carolina Health Systems provide a variety of services that aid in those successful outcomes. By leveraging the North Carolina Clinical Pharmacist Practitioner designation along with integrated health records, health system pharmacists are uniquely positioned to provide expert clinical support to patients. Services such as medication history collection, discharge medication dispensing and counseling, post discharge clinic engagement, and drug therapy management are all components of an even larger number of strategic health system pharmacy assets that aid in the care of patients whether they are admitted to hospitals, seen in clinics, or cared for in the community.


90-Day Oral Toxicity Assessment of Tropaeolum majus L. in Rodents and Lagomorphs.
Tropaeolum majus L., popularly known as nasturtium, is a species widely used in the form of infusions and salads. In the last years, the antihypertensive, diuretic, and calcium and potassium sparing activities of T. majus preparations were shown. Moreover, no preclinical 90-day oral toxicity studies were conducted. Thus, this study evaluated the toxicity of the hydroethanolic extract obtained from T. majus (HETM) leaves in female and male mice, rats, and rabbits. Swiss mice and Wistar rats were treated with HETM (75, 375, and 750 mg/kg). The doses of rabbits (30, 150, and 300 mg/kg) were calculated by allometric extrapolation. The control groups received vehicle. The animals were orally treated, daily, for 90 days. At the end, the animals were anesthetized, and body weight gain, relative weight of liver, kidney, and spleen, and histopathological changes were evaluated. Serum hematological and biochemical parameters were also analyzed. No alterations were found in body and organ weights or in histopathological and biochemical evaluation. Hematological analyses revealed small changes in lymphocytes and neutrophil counts in rats after administration of 750 mg/kg of HETM. These results showed that 90-day use of T. majus is safe in rodents and lagomorphs.


Bioaccessibility and bioactivities of phenolic compounds from roasted coffee beans during in vitro digestion and colonic fermentation.
Bioaccessibility and bioactivity of phenolic compounds in coffee beans relate to roasting and digestion process. This study aimed to estimate phenolic content, antioxidant potential, bioaccessibility, and changes in short chain fatty acids (SCFAs) production during in vitro digestion and colonic fermentation of commercial roasted (light, medium and dark) coffee beans. There was no significant difference found among all three different roasting levels. TPC and DPPH were enhanced 15 mg GAE/g and 60 mg TE/g during gastrointestinal digestion, respectively. For colonic fermentation, the highest TPC and FRAP of all coffee beans was found at 2 and 4 h, respectively. The gastric bioaccessibility of most of the phenolic compounds were relatively higher due to thermal phenolic degradation. Total SCFAs production was only up to 0.02 mM because of thermal polysaccharide decomposition. Light roasted beans exhibited relatively higher phenolic bioaccessibility, antioxidant activities and SCFAs production, which would be more beneficial to gut health.


Management and outcome of locally advanced oral squamous cell carcinoma.
Management of locally advanced OSCC is multimodal. No single therapy has been proved to be efficacious. However there is a trend towards surgical intervention in operable disease. In this review we appraise the various therapies used for the management of locally advanced OSCC. We review the literature with regards to the various treatment options for locally advanced OSCC. We categorically divided the manuscript into resectable, unresectable and technically unresectable disease. Surgery is the ideal treatment modality for resectable disease. For unresectable disease concurrent chemoradiation appears to improve survival compared to radiotherapy alone. Induction therapy might downstage tumors in the unresectable category. Targeted and Immunotherapy is reserved for recurrent, metastatic or platinum refractory OSCC. Management of locally advanced OSCC is multimodal with surgery playing the primary role. In the event where the tumor is in operable concurrent chemoradiotherapy is regarded as the best treatment modality. Induction chemotherapy currently cannot be recommended for resectable or even unresectable oral squamous cell carcinomas. However for technically unresectable disease it might play a role in improving respectability but it depends on the response of the tumor. Targeted therapy and immunotherapy is currently used for recurrent, metastatic and/or platinum refractory Head and Neck cancers. Currently it is not recommended for initial management of locally advanced disease.


GPP (Composition of Ganoderma Lucidum Poly-saccharides and Polyporus Umbellatus Poly-saccharides) Enhances Innate Immune Function in Mice.
Modern research has found that Ganoderma lucidum polysaccharides (GLP) and Polyporus umbellatus polysaccharides (PUP) mainly exhibit immunoregulation. However, the immune function of a polysaccharide composition consisting of GLP and PUP has not been studied. In this study, we developed a polysaccharide composition consisting of GLP and PUP in a ratio of 3:1 (named GPP). The immunoregulation of GPP was detected in RAW264.7 macrophages. Then, the acute oral toxicity of GPP and the effect of GPP on immunoregulation in mice was detected. The results showed that GPP enhanced the function of macrophage RAW264.7 cells through improving phagocytic ability, nitric oxide (NO) production and the mRNA expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. GPP belonged to the non-toxic grade in mice. Moreover, GPP significantly improved macrophage phagocytic function and the activity of natural killer (NK) cells after being administered to mice at a dose of 0, 3.6, 120, 360 mg/kg body weight (mg/kg BW) orally for 30 days. Taken together, these findings suggested that GPP moderately regulated immune function in mice, which contributes to the further development and utilization of GLP and PUP in immune function.


A novel selective NMDA agonist, N-phthalamoyl-L-glutamic acid (PhGA).
Ionic currents elicited by N-phthalamoyl-L-glutamic acid (PhGA) were investigated on freshly isolated hippocampal neurons with the whole-cell voltage clamp and concentration clamp techniques. PhGA elicited desensitizing inward currents in Mg(2+)-free salines only in the presence of glycine. The dose-response relationship for PhGA was close to a Langmuir isotherm with Kd = 3.7 mM and saturating level 0.75 of that for L-aspartate (L-Asp). PhGA-activated currents were blocked by Mg2+, D-2-amino-5-phosphonovalerate and kynurenate, and had the same reversal potential as L-Asp-activated currents. Complete cross-desensitization was obtained between the responses to PhGA and L-Asp. We conclude that PhGA is a new selective 'superacidic' agonist of the N-methyl-D-aspartate type of glutamate receptor.


On multichannel film dosimetry with channel-independent perturbations.
Different multichannel methods for film dosimetry have been proposed in the literature. Two of them are the weighted mean method and the method put forth by Micke et al. ["Multichannel film dosimetry with nonuniformity correction," Med. Phys. 38, 2523-2534 (2011)] and Mayer et al. ["Enhanced dosimetry procedures and assessment for EBT2 radiochromic film," Med. Phys. 39, 2147-2155 (2012)]. The purpose of this work was to compare their results and to develop a generalized channel-independent perturbations framework in which both methods enter as special cases. Four models of channel-independent perturbations were compared: weighted mean, Micke-Mayer method, uniform distribution, and truncated normal distribution. A closed-form formula to calculate film doses and the associated type B uncertainty for all four models was deduced. To evaluate the models, film dose distributions were compared with planned and measured dose distributions. At the same time, several elements of the dosimetry process were compared: film type EBT2 versus EBT3, different waiting-time windows, reflection mode versus transmission mode scanning, and planned versus measured dose distribution for film calibration and for γ-index analysis. The methods and the models described in this study are publicly accessible through IRISEU. Alpha 1.1 (http://www.iriseu.com). IRISEU. is a cloud computing web application for calibration and dosimetry of radiochromic films. The truncated normal distribution model provided the best agreement between film and reference doses, both for calibration and γ-index verification, and proved itself superior to both the weighted mean model, which neglects correlations between the channels, and the Micke-Mayer model, whose accuracy depends on the properties of the sensitometric curves. With respect to the selection of dosimetry protocol, no significant differences were found between transmission and reflection mode scanning, between 75 ± 5 min and 20 ± 1 h waiting-time windows or between employing EBT2 or EBT3 films. Significantly better results were obtained when a measured dose distribution was used instead of a planned one as reference for the calibration, and when a planned dose distribution was used instead of a measured one as evaluation for the γ-analysis. The truncated normal distribution model of channel-independent perturbations was found superior to the other three models under comparison and the authors propose its use for multichannel dosimetry.


Exercise-induced esotropia.
The authors evaluated a 34-year-old man with exercise-induced diplopia. The diagnostic testing that led to this conclusion is discussed. To the authors' knowledge, this is a rarely reported condition that warrants discussion.


B6 vitamer content of rat tissues measured by isotope tracer and chromatographic methods.
Feeding [14C]pyridoxine to growing rats for 146 days produced uniform labelling of the total vitamin B6 pool, thus permitting the radioactivity to be used as an absolute standard for evaluating the accuracy of vitamin B6 analyses. The results demonstrated that trichloroacetic acid extraction followed by cation exchange chromatography accurately measures the B6 vitamers. It is essential to homogenize tissues in a protein-denaturing agent in order to avoid shifts in the vitamer content, particularly in liver. In rats approximately 80% of the radioactivity was found in carcass and 8-9% each in liver and skin. Pyridoxamine phosphate equalled or exceeded the concentration of pyridoxal phosphate in heart, brain and kidney. The total vitamin B6 pool in weanling and adult rats averaged about 16 nmol/g body wt. Meta-phosphoric acid extraction followed by reverse phase chromatography gave good agreement with the cation exchange method in rat liver but with cat plasma yielded pyridoxal phosphate values below those of the cation exchange or enzymatic methods. The discrepancies encountered between different homogenization techniques and chromatographic methods emphasize the need for constant vigilance and continual verification of results by independent methods.


Morbidity from 5 to 10 years.
The prevalence and incidence of illness was examined in a birth cohort of Christchurch children studied during the age range of 5-10 years. At this age, children had an average of 12 consultations with family doctors; 26% were admitted to hospital and 53% made one or more attendances at hospital outpatient departments. The majority of general practitioner contacts involved five groups of conditions: respiratory illness; integumental lesion; accidents; gastrointestinal conditions; and hearing problems. Hospital admissions were dominated by five types of admission: respiratory illness; accidents; gastrointestinal conditions; genito-urinary problems; musculoskeletal problems. More than two-thirds of outpatient attendances were accounted for by accidents, respiratory illness, musculoskeletal problems, vision problems, and hearing problems. Trends in rates of medical consultation for accidents and respiratory illness during the period from birth to 10 years are described and the implications of the findings are discussed.


Health literacy from the perspective of African immigrant youth and elderly: a PhotoVoice project.
This project examines the views of African immigrants on health, access to health resources in the U.S., and perceived barriers to a healthy wellbeing faced by the elderly immigrants in the community. PhotoVoice methodology was used to evaluate the views of African immigrant youths and elderly drawn from a convenience sample. Participants were trained on the use of cameras and guided by research questions while taking photographs. The photographs were analyzed, coded into themes and presented to community resource representatives at a photo exhibit. Emergent themes were: 1) nutrition, obesity and physical activity; 2) occupational regulation and educational opportunities; 3) feeling of security and public safety; 4) ethno-racial diversity and the health care system; 5) religiosity and social well-being. These results have implications for health care professionals and community agencies serving immigrant populations. A deeper look into the health issues affecting this population is essential.


Lactate and pyruvate production in isolated thiamine-deficient rat diaphragm strips.
Rats were maintained on a thiamine-deficient diet to deplete skeletal muscle of thiamine pyrophosphate, and thus decrease the oxidative metabolism of pyruvate. The blood lactate concentration was significantly elevated in thiamine-deficient (TD) animals when compared with pair-fed (TP) controls. Analysis of diaphragm strips from these animals revealed that tissue lactate and pyruvate concentrations were not affected by any of the treatments employed. The rate of lactate efflux from TD tissues was, however, twice that from TP and 4.5 times that from weight-control (WC) tissues. The H+ efflux rate was also much greater in the TD muscle preparation than either of the control groups. Following 3 min of stimulation (150-Hz, 200-ms pulse train every 0.5 s), the degree of fatigue of tissues from each of these three treatment groups was not different. The observation in this study that glycolysis becomes the predominant metabolic pathway in thiamine deficiency without increasing the intracellular level of products, indicates that this treatment also has other effects which increase the effective lactate permeability of the fibre membranes.


[Utility of low light level television cameras for the fluorescein angiography of the retina (author's transl)].
A survey of the major proportion of low-light level TV cameras available on the German market is described. A comparison and an assessment of the applicability of televised fluorescein angiography were carried out with the aid of technical data and measured results. It became evident that some systems were practicable for clinical use. With those it was possible to record angiograms at minimal illumination levels and patient inconvenience was reduced significantly. Measurements of blood flow parameters were possible with good temporal and geometrical resolution and full reproducibility.


Genome rearrangements caused by depletion of essential DNA replication proteins in Saccharomyces cerevisiae.
Genetic screens of the collection of ~4500 deletion mutants in Saccharomyces cerevisiae have identified the cohort of nonessential genes that promote maintenance of genome integrity. Here we probe the role of essential genes needed for genome stability. To this end, we screened 217 tetracycline-regulated promoter alleles of essential genes and identified 47 genes whose depletion results in spontaneous DNA damage. We further showed that 92 of these 217 essential genes have a role in suppressing chromosome rearrangements. We identified a core set of 15 genes involved in DNA replication that are critical in preventing both spontaneous DNA damage and genome rearrangements. Mapping, classification, and analysis of rearrangement breakpoints indicated that yeast fragile sites, Ty retrotransposons, tRNA genes, early origins of replication, and replication termination sites are common features at breakpoints when essential replication genes that suppress chromosome rearrangements are downregulated. We propose mechanisms by which depletion of essential replication proteins can lead to double-stranded DNA breaks near these features, which are subsequently repaired by homologous recombination at repeated elements.


Surgical management of hemodialysis patients.
Ophthalmic surgeons can expect increased opportunities in the future to treat patients who undergo maintenance hemodialysis. Such patients often present with complex medical problems and carry high risk factors for surgery. Nevertheless, the full range of ophthalmic surgical procedures can be accomplished without increased morbidity when patient management is carefully organized between the ophthalmologist and nephrologist. In this report the physiology of the functionally anephric patient is reviewed. Attention is directed to the most commonly encountered complications: systemic hypertension, uremia, electrolyte imbalance, drug toxicity, and arteriovenous fistula thrombosis. Specific guidelines are then presented to reduce the risk of complications at each phase of hospitalization.


Matrix solid phase dispersion-Soxhlet simultaneous extraction clean-up for determination of organochlorine pesticide residues in tobacco.
A novel method combining matrix solid phase dispersion (MSPD) with Soxhlet simultaneous extraction clean-up (SSEC) was developed. Being a single-step extraction and clean-up procedure, it could be used instead of multistep solvent extraction and Florisol column clean-up. It not only reduces sample contamination during the procedure, but it also decreases the amount of organic solvent needed. The retention times of standards were used to qualitatively assess the method, and the external standard method was used to quantitatively assess it. Residues of organochlorine pesticides (OCP) in tobaccos were determined by gas chromatography-electron capture detection (GC-ECD), and their identities were confirmed by the standard addition method (SAM). The performance of the method was evaluated and validated: the detection limit was 0.01-0.02 microg g(-1), relative standard deviations were 5-26%, and recoveries were 72-99% at fortification levels of 0.10, 1.00 and 10.0 microg g(-1). The analytical characteristics of MSPD-SSEC compared very favorably with the results from the classical multistep solvent extraction and Florisol column clean-up method.


Normal high-resolution cerebral 99mTc-HMPAO SPECT scans in symptomatic neonates exposed to cocaine.
Vascular constriction is said to account for a variety of clinical effects of cocaine. High-resolution 99mTc-hexamethylpropylene amine oxime single photon emission computed tomographic (SPECT) scans, which measure cerebral blood flow, were used to determine whether neonatal brain perfusion deficits are present in newborns with confirmed cocaine exposure. Normal, age-appropriate SPECT scans were found in 21 babies. Conventional neuroimaging was also performed when possible. All but one of the 14 magnetic resonance imaging (MRI) scans and one computed tomographic scan were normal. One MRI showed a mild delay in myelination. All but four neonates had behavioral or electroencephalographic abnormalities, and microcephaly was found in five of 21. The normal neonatal SPECT scans contrast with findings in adult cocaine users, which typically report abnormal findings of cerebral hypoperfusion. This study identifies a unique lack of corresponding cerebral vascular pathology in symptomatic neonates. It raises the possibility that many of these children can escape significant ischemic injury.


Facile, efficient, and diastereoselective synthesis of heterohelicene-like molecules.
A concise and efficient route to new and interesting heterohelicene-like molecules has been developed through the one-pot, cascade reductive coupling reaction of o-hydroxydiimines or o-nitrodiimines and triphosgene in the presence of TiCl4/Sm. Purification of the final products only required a single recrystallization leading to high purity. High diastereoselectivity was also achieved, and two structures of the final products were confirmed by X-ray diffraction analysis.


Triphenylsilyl- and trityl-substituted carbazole-based host materials for blue electrophosphorescence.
Carbazole-based materials adopting the nonconjugated substitution of triphenylsilyl (-SiPh(3)) and trityl (-CPh(3)) side groups are studied as high-triplet-energy, morphologically, and electrochemically stable host materials with tunable carrier-transport properties for organic blue electrophosphorescence. The developed host materials 9-(4-tert-butylphenyl)-3,6-bis(triphenylsilyl)-9H-carbazole (CzSi), 9-(4-tert-butylphenyl)-3,6-ditrityl-9H-carbazole (CzC), and 9-(4-tert-butylphenyl)-3-(triphenylsilyl)-6-trityl-9H-carbazole (CzCSi) all show high triplet energies of 2.97-3.02 eV, along with high glass transition temperatures of 131-163 degrees C and superior electrochemical stability. Nevertheless, the carrier-transport properties show rather significant dependence on different substitutions. Although three different host materials give similar peak electroluminescence efficiencies at low driving currents, the CzSi host, which has more suitable carrier-transport properties, renders broadened distributions of the triplet excitons in phosphorescent devices, reducing the quenching associated with triplet-triplet annihilation and giving larger resistance against efficiency roll-off at higher brightnesses.


The ownership elephant: ownership and community-governance in primary care.
Ownership of primary care is an often neglected but important health systems design parameter. The New Zealand Primary Health Care Strategy has established Primary Health Organisations (PHOs) as non-profit umbrella organisations, however in most instances their constituent general practices are for-profit small businesses. This viewpoint paper aims to: (a) define ownership and community participation; (b) summarise some of the evidence from the NatMedCa study pertaining to ownership-related differences; and (c) discuss the policy implications of different ownership forms in primary care, and the implications of merging different ownership forms under the umbrella of PHOs. Ownership confers governance responsibility (ultimate control) for an organisation, and accountability for its actions. Community governance involves vesting overall control of resources in users and the community, rather than with health service managers or health professionals. Results from three studies using the NatMedCa survey indicate that community-governed non-profits in New Zealand differ in a number of respects from their for-profit counterparts. As non-profit and for-profit ownership forms have different social roles, and as meaningful community participation in governance is determined in large part by ownership structures, there is a need for ownership frameworks to be used more widely in health policy making. Because of the ownership boundary that exists between non-profit community-governed PHOs and their constituent for-profit general practices PHOs may have little real ability to effectively govern their practices.


Sciatic hernia with an early-stage adenocarcinoma of the appendix: report of a case.
Sciatic hernia and early-stage appendiceal adenocarcinoma are rare disorders. We report herein a case of an early stage of appendiceal adenocarcinoma found incidentally during an operation for sciatic hernia. An 80-year-old woman was admitted to our hospital with abdominal distension. Abdominal computed tomography showed a small bowel obstruction and a small bowel loop through the right sciatic foramen outside the pelvic cavity. During an operation for the repair of the sciatic hernia, a deformed appendix was found incidentally and a simple appendectomy was also performed. Histological examination of the excised appendix showed well-differentiated adenocarcinoma confined to the mucosal layer in a tubulo-villous adenoma. At 13-month follow-up, the patient is doing well without evidence of recurrence or metastasis.


ULTRASOUND GUIDED FOAM SCLEROTHERAPY - THE SIMPLEST, LEAST INVASIVE, AND CHEAPEST METHOD FOR VARICOSE VEIN TREATMENT.
The aim is to present our experience and observations regarding varicose vein treatment by means of ultrasound guided foam sclerotherapy (UGFS). The study included 81 patients, 54 with insufficient main stem superficial veins in one limb and 27 with both limbs affected. Great saphenous vein insufficiency was diagnosed in 68, small saphenous insufficiency in 18, anterior accessory saphenous vein insufficiency in 11, and Giacomini vein insufficiency in 3 limbs. Seven limbs had combined insufficiency of great saphenous vein and small saphenous vein, and 1 limb had combined insufficiency of Giacomini vein and small saphenous vein. UGFS was employed to treat main stem vein reflux and their tributaries. Within a month after treatment, all main stem veins were occluded and only small corrections were performed occasionally to treat residual varices. Regarding side effects, skin darkening and hard lumps at the sites of varicose veins were most commonly observed. We also recorded several episodes of thrombophlebitis. Few patients experienced dry cough, visual disturbances and headache following the treatment. After six months, repeat UGFS of main stem veins had to be performed in few patients. Very few patients expressed dissatisfaction a year after treatment, mainly because of residual skin darkening. In conclusion, UGFS proved to be the simplest, quickest and cheapest method of varicose vein treatment. According to our experience, it yielded satisfactory functional and cosmetic results. Side effects do occur, but are acceptable, in particular at long term.


A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta.
The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. Further studies revealed that, upon syncytialization, human chorionic gonadotropin reduced the phosphorylation of retinoblastoma protein (pRB) via activation of the cAMP/PKA pathway, which sequesters E2F transcription factor 1 (E2F1), the transcription factor for EZH2 expression. As a result of inactivation of the pRB-E2F1-EZH2 pathway, the repressive marker trimethylation of histone H3 lysine 27 at the 11β-HSD2 promoter is removed, which leads to the robust expression of 11β-HSD2 during syncytialization.


[Calcium metabolism and anti-aging of bone].
Age-dependent change in calcium metabolism is affected by nutritional factors like calcium and vitamin D as well as by endocrine factors including parathyroid hormone. Because calcium deficiency could deteriorate bone metabolisms and cardiovascular systems, adequate intakes of calcium and vitamin D are important for anti-aging.


MiR-122 decreases HCV entry into hepatocytes through binding to the 3' UTR of OCLN mRNA.
Analysis in silico suggests that occludin (OCLN), a key receptor for HCV, is a candidate target of miR-122; the most abundant hepatic micro RNA. We aimed to determine if miR-122 can decrease HCV entry through binding to the 3' UTR of OCLN mRNA. Huh7.5 cells were cotransfected with luciferase construct containing 3' UTR of OCLN (pLuc-OCLN) and with selected miRNAs (0-50 nM) and luciferase activity was measured. Huh7.5 cells were also infected by viral particles containing lenti-miR122 genome or control virus. After 48 h, the cells were infected with HCV pseudo-particles (HCVpp) and VSV pseudo-particles (VSVpp). After 72 h of infection, luciferase activity was measured and HCVpp activity was normalized to VSVpp activity. miR-122 binds to the 3'-UTR of OCLN and down-regulates its expression; cotransfection of miR-122 mimic with pLuc-OCLN resulted in a significant decrease in luciferase activity [by 55% (P < 0.01)], while a non-specific miRNA and a mutant miR-122 did not have any effect. miR-122 mimic significantly down-regulated [by 80% (P < 0.01)] OCLN protein in Huh7.5 cells. Accordingly, patients with chronic hepatitis C and higher levels of hepatic miR-122 have lower hepatic expression of OCLN. Immuno-fluorescence imaging showed a decrease in colocalization of OCLN and CLDN following miR-122 over-expression in HCV infected cells. Huh7.5 cells transiently expressing Lenti-miR122 system showed 42% (P < 0.01) decrease in HCV entry. This study uncovers a novel antiviral effect of miR-122 on human liver cells and shows that over-expression of miR-122 can decrease HCV entry into hepatocytes through down-regulation of OCLN.


At-home computerized executive-function training to improve cognition and mobility in normal-hearing adults and older hearing aid users: a multi-centre, single-blinded randomized controlled trial.
Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults. A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45-60 years old) and older adults (65-80 years old), as well as older hearing aid users (65-80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE's StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia's PERFORM Centre. This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss. Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998.


[Several anatamo-anthropologic features of the bones of the forearm].
Corpses of 242 Lithuanians died at the age of 14-95 years from Kaunas and its environs have been studied somatometrically . The forearm bones from the corpses have been extracted, macerated and studied osteoscopically by means of a stereomicroscope, osteometrically and electroroentgenographically . The data obtained are treated by means of a computer. The signs of lateral asymmetry in the forearm bones, that is more often right-sided, are described. Sex differences in the forearm bones are also described. These differences could be used as a base for the method of sex determination by means of discriminant functions. Age differences of the bones studied are presented.


Neonatal outcomes of preterm or very-low-birth-weight infants over a decade from Queen Mary Hospital, Hong Kong: comparison with the Vermont Oxford Network.
There is a paucity of local data on neonatal outcomes of preterm/very-low-birth-weight infants in Hong Kong. This study aimed to evaluate the survival rate on discharge and morbidity of preterm/very-low-birth-weight infants (≤29+6 weeks and/or birth weight <1500 g) over a decade at Queen Mary Hospital in Hong Kong, so as to provide centre-specific data for prenatal counselling and to benchmark these results against the Vermont Oxford Network. Standardised perinatal/neonatal data were collected for infants with gestational age of 23+0 to 29+6 weeks and/or birth weight of <1500 g who were born at Queen Mary Hospital between 1 January 2005 and 31 December 2014. These data were compared with all neonatal centres in the Vermont Oxford Network in 2013. The Chi squared test was used to compare the categorical Queen Mary Hospital data with that of Vermont Oxford Network. A two-tailed P value of <0.05 was considered statistically significant. The overall survival rate on discharge from Queen Mary Hospital for 449 infants was significantly higher than that of the Vermont Oxford Network (87% versus 80%; P=0.0006). The morbidity-free survival at Queen Mary Hospital (40%) was comparable with the Vermont Oxford Network (44%). At Queen Mary Hospital, 86% of infants had respiratory distress syndrome, 40% bronchopulmonary dysplasia, 44% patent ductus arteriosus, 7% severe intraventricular haemorrhage, 5% necrotising enterocolitis, 10% severe retinopathy of prematurity, 10% late-onset sepsis, and 84% growth failure on discharge. Rates of respiratory distress syndrome, intraventricular haemorrhage, necrotising enterocolitis, and severe retinopathy of prematurity were similar in the two populations. At Queen Mary Hospital, significantly more infants had bronchopulmonary dysplasia (P=0.011), patent ductus arteriosus (P=0.015), and growth failure (P=0.0001) compared with the Vermont Oxford Network. In contrast, rate of late-onset sepsis was significantly lower at Queen Mary Hospital than the Vermont Oxford Network (P=0.0002). Mortality rate and most of the morbidity rates of our centre compare favourably with international standards, but rates of bronchopulmonary dysplasia and growth failure are of concern. A regular benchmarking process is crucial to audit any change in clinical outcomes after implementation of a local quality improvement project.


[Legal welfare for lawbreakers with mental retardation].
In Japan, most lawbreakers with psychiatric disorders are committed to hospital by order of the relevant prefectural governor under the Mental Health Act. This can be called the "compulsory treatment policy" for psychiatric patients. On the other hand, most law-breakers with mental retardation (except those with severe and profound retardation) are prosecuted and sentenced to imprisonment under the Criminal Law. This can be called the "strictly judicial policy" for mildly or moderately retarded people. In my opinion, instead of either compulsory treatment or strict justice, "compassionate justice", or welfare support in the field of justice, is crucial to protect individuals with psychiatric disorders and/or mental retardation from the stigma of criminality.


Integration of an Independent Monitor Unit Check for High-Magnetic-Field MR-Guided Radiation Therapy System.
Commercial independent monitor unit (IMU) check systems for high-magnetic-field MR-guided radiation therapy (RT) systems are lacking. We investigated the feasibility of adopting an existing treatment planning system (TPS) as an IMU check for online adaptive radiotherapy using 1.5-Tesla MR-Linac. The 7-MV flattening filter free (FFF) beam and multi-leaf collimator (MLC) models of a 1.5-T Elekta Unity MR-Linac within Monte Carlo-based Monaco TPS were used to generate an optimized beam model in Eclipse TPS. The MLC dosimetric leaf gap of the beam in Eclipse was determined by matching the dose distribution of Eclipse-generated intensity-modulated radiation therapy (IMRT) plans using the Analytical Anisotropic Algorithm (AAA) algorithm to Monaco plans. The plans were automatically adjusted for different source-to-axis distances (SADs) between the two systems. For IMU check, the treatment plans developed in Monaco were transferred to Eclipse to recalculate the dose using AAA. A plug-in within Eclipse was created to perform a 2D gamma analysis of the AAA and Monte Carlo dose distribution on a beam's eye view parallel plane. Monaco dose distribution was shifted laterally by 2 mm during gamma analysis to account for the impact of magnetic field on electron trajectories. Eclipse doses for posterior beams were corrected for both the Unity couch and the posterior MR coil attenuation. Thirteen patients, each with 4-5 fractions for a variety of tumor sites (pancreas, rectum, and prostate), were tested. After thorough commissioning, the method was implemented as part of the standard clinical workflow. A total of 62 online plans, each with approximately 15 beams, were evaluated. The average per-beam gamma (3%/3 mm) pass rate for plans was 97.9% (range, 95.9% to 98.8%). The average pass rate per beam for all 932 beams used in these plans was 97.9% ± 1.9%, with the lowest per-beam gamma pass rate at 88.4%. The time for the process was within 3.2 ± 0.9 min. The use of a second planning system provides an efficient way to perform IMU checks with clinically acceptable accuracy for online adaptive plans on Unity MR-Linac. This is essential for meeting the safety requirements for second checks as outlined in American Association of Physicists in Medicine Task Group (AAPM TG) reports 114 and 219.


Relationship between cytosol TPS, TPA and cell proliferation.
The serological tumor marker tissue polypeptide antigen (TPA) and the more recently identified tissue-specific polypeptide antigen (TPS) have been reported to be indicators of the proliferation rate of the tumor. In the present investigation we compared the cytosol level of the two markers with the proliferative activity of the tumor measured using the 3H-thymidine labelling index. The preliminary results presented here show that higher TLI is associated with lower cytosol levels of both TPA and TPS. TPA and TPS in the cytosol were significantly associated. These findings are in agreement with the previously demonstrated association between high TPA cytosol levels and better prognosis in breast cancer. Further studies are ongoing in order to: 1. confirm these findings in a larger patient series; 2. investigate any possible prognostic indication provided by TPS; 3. evaluate any possible biological meaning of the negative association between TPA/TPS and TLI in the cytosol of breast cancer.


Tricyclic antidepressants versus electroconvulsive therapy: a review of the evidence for efficacy in depression.
The author examines the thesis that electroconvulsive therapy is superior to tricyclic antidepressants in treating nonpsychotic major depression. Every study published in English since 1960 comparing electroconvulsive therapy against tricyclics in treating this condition was reviewed. Because of numerous methodological weaknesses in the studies, the data is inadequate to support the claim that one treatment is superior to the other.


Early and late selection in unconscious information processing.
In four experiments, we investigated whether masked stimuli in priming experiments are subjected to early or to late selection. In Experiment 1, participants classified four target-pictures as being small or large. In line with early selection accounts, prime-pictures with a different perceptual appearance as the experienced targets did not elicit congruency effect. In Experiment 2, 40 targets all depicting animals were presented. Results were in line with late selections assumptions because novel animal primes but not novel primes from different semantic categories yielded congruency effects. In Experiment 3, the targets were chosen such that there is a second semantic feature that covaried with the required response. Here, novel primes picturing small animals did not influence target responses with regard to the instructed size classification, but with regard to their affiliation to the category animal. In Experiment 4, small and large pictures from two categories were presented. Category match did not influence priming, ruling out that feature overlap contaminated the former results. The results indicate that participants' prestimulus expectations determine in which stage in the processing-stream masked stimuli are selected.


Stimulation of insulin secretion by infusion of free fatty acids.
The acute elevation of plasma free fatty acid (FFA) levels by direct infusion of sodium oleate into the plasma of conscious dogs was accompanied by the rapid onset of a 2- to 12-fold increase in plasma immunoreactive insulin, and, subsequently, a marked fall in plasma glucose, even in dogs receiving intravenous glucose throughout the infusion. The magnitude of both the insulin and glucose responses correlated with the mean FFA level during infusion. A large increase in plasma insulin and fall in glucose also occurred when glycerol was infused with oleate in order to simulate endogenous lipolysis more closely. Insulin levels in pancreaticoduodenal vein blood rose markedly during oleate infusion, while plasma ketone levels rose only slightly. In contrast to the effects of oleate infusion, elevation of plasma FFA to correspondingly high levels by triolein ingestion and intravenous heparin produced only small increases in plasma insulin, which did not correlate well with the FFA level reached, and small increases in plasma glucose.The results indicate that under certain conditions elevated FFA levels may be a potent stimulus of insulin secretion. This response is modified under other conditions such as during chylomicron removal under the influence of heparin. This effect may play a role in the regulation of lipolysis and ketone formation, but determination of the exact mechanism of FFA stimulation of the pancreas and its physiological significance will require further investigation.


Treatment options after failure of radiation therapy-a review.
Radioresistant or recurrent prostate cancer represents a serious health risk for approximately 20%-30% of patients treated with primary radiation therapy for clinically localized prostate cancer. The majority of patients exhibit large volume and poorly differentiated disease at the time of diagnosis, which limits the ability of salvage therapy to eradicate the cancer. Early detection with serum PSA monitoring and prostate needle biopsy following primary radiation therapy may identify residual adenocarcinoma at an earlier stage and increase the likelihood of successful salvage therapy. Radical prostatectomy, prostate cryoablation, and brachytherapy comprise the options for salvage treatment available for radiorecurrent prostate cancer. The goal of disease eradication must be balanced against the potential for serious treatment-related side effects. As a result, many patients receive noncurative therapy with androgen ablation despite the real risk of disease progression and mortality.


A network analysis on biopsychosocial factors and pain-related outcomes assessed during a COVID-19 lockdown.
Psychological stress, social isolation, physical inactivity, and reduced access to care during lockdowns throughout a pandemic negatively impact pain and function. In the context of the first COVID-19 lockdown in Spain, we aimed to investigate how different biopsychosocial factors influence chiropractic patients' pain-related outcomes and vice-versa. A total of 648 chiropractic patients completed online questionnaires including variables from the following categories: demographics, pain outcomes, pain beliefs, impact of the COVID-19 pandemic, stress/anxiety and self-efficacy. Twenty-eight variables were considered in a cross-sectional network analysis to examine bidirectional associations between biopsychosocial factors and pain outcomes. Subgroup analyses were conducted to estimate differences according to gender and symptom duration. The greatest associations were observed between pain duration and pain evolution during lockdown. Participants' age, pain symptoms' evolution during lockdown, and generalized anxiety were the variables with the strongest influence over the whole network. Negative emotions evoked by the pandemic were indirectly associated with pain outcomes, possibly via pain catastrophizing. The network structure of patients reporting acute pain showed important differences when compared to patients with chronic pain. These findings will contribute to identify which factors explain the deleterious effects of both the pandemic and the restrictions on patients living with pain.


Intraaortic Balloon Pump Counterpulsation, Part I: History, Technical Aspects, Physiologic Effects, Contraindications, Medical Applications/Outcomes.
Intraaortic balloon pump counterpulsation is the most common form of mechanical circulatory support used in patients with myocardial ischemia and cardiogenic shock. The physiologic principles of counterpulsation include diastolic augmentation of aortic pressure and systolic reduction of left ventricular afterload, resulting in hemodynamic benefits through increased coronary perfusion pressure and improved myocardial oxygen balance in patients with myocardial ischemia. Major trials have failed to conclusively demonstrate improvements in morbidity and mortality with counterpulsation therapy for patients with acute myocardial infarction (MI), cardiogenic shock, and/or severe coronary artery disease undergoing revascularization therapy, and the debate over its applications continues. Part I of this review focuses on the history of the development of counterpulsation, technical considerations, and complications associated with its use, its physiologic effects, and evidence for its use in myocardial ischemia and cardiogenic shock.


Intralesional 5-fluorouracil as a management for cutaneous squamous cell carcinomas: A rural Australian retrospective case series.
While the gold standard treatment for cutaneous squamous cell carcinomas (cSCCs) is surgical removal, there is a risk of infection, cosmetic and functional deficits. Intralesional 5-fluorouracil (5-FU) has been shown to be a potential non-surgical treatment modality for cSCCs in the literature. The aim was to investigate the safety and feasibility of using intralesional 5-FU to treat cSCCs. A literature review was conducted and a retrospective case series analysed patients who commenced intralesional 5-FU treatment for at least one cSCC between 1 January 2018 and 1 January 2019 at a private clinic in Orange, Australia. Inclusion criteria include: at least one cSCC was treated; only intralesional 5-FU was used; and treatment was ceased due to complete or inadequate remission, or adverse effects. There were 15 patients (7 female, 8 male, 60-99 years) and 20 out 21 cSCC lesions (82.6%) cleared while one lesion (4.3%) recurred. Six lesions (26.1%) ulcerated, four lesions became infected (17.4%) and one patient had an allergic reaction. The average number of treatments required for clearance was four (range 1-35), and the average 5-FU dose used was 75 mg (range 50-150 mg). Across 25 studies, 656 out of 708 lesions cleared (92.66%). Adverse effects were self-limiting and mostly well-tolerated. Intralesional 5-FU is an affordable and non-invasive non-surgical treatment modality that appears feasible to use for cSCCs and has a relatively low treatment-associated morbidity. Future clinical trials can help develop a protocol to guide clinicians in its use.


Transcription and DNA replication of sperm nuclei introduced into blastomeres of 2-cell mouse embryos.
The aim of this study was to investigate the behaviour of sperm nuclei in the cytoplasm of the 2-cell mouse embryo. To this end, we produced hybrids between anucleate fertilised oocyte fragments and blastomeres of the 2-cell embryos. When sperm nuclei at the stage of decondensation or recondensation were introduced into blastomeres the development of male pronuclei was usually retarded and they never reached the size of the blastomere nuclei. These abortive male pronuclei were unable to initiate transcription but they were capable of synthesising DNA. The majority of sperm nuclei introduced into blastomeres as early male pronuclei developed normally and reached the size of the blastomere nuclei. They synthesised DNA simultaneously with blastomere nuclei and were transcriptionally active. In addition they participated in the cleavage division of hybrid cells. This shows that the very early male pronucleus when transmitted from the oocyte cytoplasm to the blastomere cytoplasm can respond positively to the new cytoplasmic factors, i.e. it undertakes both DNA replication and transcription according to the time schedule characteristic of the second cell cycle.


IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation.
Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.


Experimental approach for assessing the outcome accuracy of antibody microarray experiments.
An experimental strategy for quality control of antibody microarray analyses is proposed. The method utilizes proteins that are prepared for regular antibody microarray experiments. There is no need to use exogenous positive or negative reference markers and no need to determine the absolute concentration of each individual protein in the sample. Validation experiments support the basic principle of the proposed approach. This method can be a useful tool for assessing the outcome accuracy of microarray experiments.


Renal vascular effects of epinephrine infusion in the halothane-anesthetized piglet.
The objective of this study was to determine the dose-response effects of epinephrine, given by systemic intravenous infusion to the halothane-anesthetized newborn piglet, on renal blood flow, mean arterial blood pressure, and renal vascular resistance. Seven newborn piglets were acutely instrumented. A transit-time ultrasound flow probe was placed around the renal artery and a femoral arterial catheter was placed for blood pressure monitoring. Epinephrine was infused in doubling doses from 0.2 to 3.2 micrograms.kg-1.min-1. Mean arterial blood pressure increased from 54 mmHg (1 mmHg = 133.3 Pa) to an average of 96 mmHg at 3.2 micrograms.kg-1.min-1 of epinephrine. Renal blood flow increased from 165 mL.min-1 x 100 g-1 at baseline to 185 mL.min-1 x 100 g-1 at a dose of 0.2 microgram.kg-1.min-1 and increased further at 0.4 and 0.8 micrograms.kg-1.min-1 to reach 261 mL.min-1 x 100 g-1. Renal blood flow began to fall at a dose of 3.2 micrograms.kg-1.min-1, remaining however, significantly above baseline (211 mL.min-1 x 100 g-1). Consequently, calculated renal vascular resistance fell as the dose was increased from 0.2 to 0.8 micrograms.kg-1.min-1 and then rose again at 1.6 and 3.2 micrograms.kg-1.min-1, being significantly above baseline at 3.2 micrograms.kg-1.min-1. These results demonstrate that epinephrine when given by systemic infusion to the halothane-anesthetized newborn pig is a renal vasodilator at low doses and causes renal vasoconstriction at moderate to high doses. Renal blood flow remained above baseline at all doses tested, and thus, within the dosage range tested, epinephrine infusion should not cause renal ischemia.


Isolation of 1-Methylherbipoline Salts of Halisulfate-1 and of Suvanine as Serine Protease Inhibitors from a Marine Sponge, Coscinoderma mathewsi
Bioassay-guided isolation of serine protease inhibitors from a marine sponge, Coscinoderma mathewsi, has yielded 1-methylherbipoline salts of halisulfate-1 and of suvanine. Structures of these compounds were identified by spectroscopic analyses and literature data. Antithrombin and antitrypsin activity was determined.


Interventions in chronic low back pain.
Chronic low back pain presents a major challenge for general practitioners and is a significant drain on community resources. Patients often feel frustrated by modern medicine's apparent failure to validate their symptoms with a specific diagnosis and management plan. This article presents an evidence based guide to current interventions, including an algorithm for the interventional diagnostic workup of low back pain that has persisted beyond 3 months. Modern imaging techniques rarely determine the cause of pain. The GP must look for 'red flag' clues in the history. Management of low back pain includes NSAIDs, simple injections of plain local anaesthetic without adrenalin or cortisone, referral to a masseuse, cortisone, physiotherapist and/or a musculoskeletal pain physician. Specific management includes medial branch and sacroiliac joint blocks, and radiofrequency neurotomy. Patients with long term pain may be referred to a psychologist for cognitive behavioural therapy.


Quantitation of bidirectional shunt from a single dye-dilution curve.
A method for quantitating intracardiac bidirectional shunt and estimating its blood flow is presented. Three curves, defined as "right-to-left shunt curve", "normal pathway curve", and "left-to-right shunt curve" were separately drawn from the original downstream dye-dilution curve, and their areas ?A'', A, A', respectively, were calculated in the conventional manner. A'/A showed left-to-right shunt ratio (QL-R%) even in the presence of right-to-left shunt. However, right-to-left shunt ratio (QR-L%) was given by (1-A'/A)/(A/A'' + 1--A'/A), and equalled A''/(A + A'') only when left-to-right shunt was absent (A' equals O). A''/(A + A) should become increasingly higher than QR-L% with rise in QL-R% (equals A'/A). The relationship between A''/(A + A'') and QR-L% for various A/A isopleths is shown by figure. A good agreement (r equals 0.848, p less than 0.001) was found between QL-R% values by the present method and those calculated by the oxygen method. In contrast, QR-L% values by the present method were consistently lower than those by the oxygen method; the difference was exaggerated especially in cases with history of cardiac failure, and these cases tended to show lower systemic flow. The average difference in QR-L% between the two methods, found in cases free from failure, was 7 per cent. This was thought to be ascribed to intrapulmonary physiological shunt.


Sequencing nothing: Exploring failure modes of nanopore sensing and implications for life detection.
The detection of extant life is a major focus of many planned future planetary missions, a current challenge of which is the ability to target biomarkers capable of providing unambiguous evidence of life. DNA sequencing is increasingly recognized as a powerful tool for life detection for planetary exploration missions; beyond use of sequence information to determine the origins of the sample (e.g., extant life or forward contamination), recent advances in the field have enabled interrogation of single molecules, with or without amplification. The focus of this work is on failure modes, specifically the issues encountered when there is no-to-low input DNA into a sequencing device, and the potential for the generation of sequencing artifacts that could be interpreted as a false positive. Using Oxford Nanopore Technologies (ONT) MinION, we assess whether single molecule sequencing, involving no amplification, generates noise signals that could be misinterpreted in the context of a planetary exploration mission, and also whether the ability of the instrument to handle these types of situations could make it feasible for clean room monitoring. Utilizing quality score filtering techniques in place at the time of this experiment, runs containing only initial flowcell chemistry and/or library reagents generated 5 passing reads out of a total of 3568 measured reads, and contained estimated sequences with low complexity that did not map to the NCBI database. The noise characteristics in all instances suggest that quality thresholds were appropriately chosen by ONT: new chemistry and basecalling workflows have shown further suppression of noise sources, which completely mitigate the generation of spurious reads.


Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves.
The objective of this study was to determine the effects of feeding protein-iron complex (PIC) on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf's life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast). Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose) 10 g/day calf of protein-iron complex, HFe (height iron dose) 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC), saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC), which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS) and glutathione peroxidase activity (GPx). Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs.