Review and management of breast lesions detected with breast tomosynthesis but not visible on mammography and ultrasonography.
Background Breast tomosynthesis is more sensitive than mammography and can detect lesions that are not always visible with conventional methods such as digital mammography (MG) and ultrasonography (US). No standardized approach is available for the management of lesions that are detectable with tomosynthesis but are not visible on MG or US. Purpose To review suspicious breast lesions detected with tomosynthesis but not visible on two-dimensional (2D) MG or US and to determine the management options for these lesions. Material and Methods Ethical committee approval was obtained. The radiological records, biopsy or surgery results, and follow-up findings of 107 patients who had a tomosynthesis-positive but MG- or US-negative breast lesion between 2011 and 2016 were retrospectively evaluated. Results Of 107 lesions visible only with tomosynthesis, 74% were architectural distortions and 26% were asymmetrical opacities. All patients underwent magnetic resonance imaging (MRI) for further evaluation. Among the 48 (45%) MRI-negative lesions, none had a suspicious alteration during the follow-up period. Among the MRI-positive lesions, 28% of the 50 architectural distortions and 11% of the nine asymmetrical opacities were malignant. Conclusion Given the inherent high false-positive rate of breast tomosynthesis, breast MRI prior to biopsy may reduce the number of unnecessary biopsies for suspicious breast lesions that are tomosynthesis-positive only.


Use of Targeted High-Throughput Sequencing for Genetic Classification of Patients with Bleeding Diathesis and Suspected Platelet Disorder.
Inherited platelet disorders (IPD) form a rare and heterogeneous disease entity that is present in about 8% of patients with non-acquired bleeding diathesis. Identification of the defective cellular pathway is an important criterion for stratifying the patient's individual risk profile and for choosing personalized therapeutic options. While costs of high-throughput sequencing technologies have rapidly declined over the last decade, molecular genetic diagnosis of bleeding and platelet disorders is getting more and more suitable within the diagnostic algorithms. In this study, we developed, verified, and evaluated a targeted, panel-based next-generation sequencing approach comprising 59 genes associated with IPD for a cohort of 38 patients with a history of recurrent bleeding episodes and functionally suspected, but so far genetically undefined IPD. DNA samples from five patients with genetically defined IPD with disease-causing variants in WAS , RBM8A , FERMT3 , P2YR12 , and MYH9 served as controls during the validation process. In 40% of 35 patients analyzed, we were able to finally detect 15 variants, eight of which were novel, in 11 genes, ACTN1 , AP3B1 , GFI1B , HPS1 , HPS4 , HPS6 , MPL , MYH9 , TBXA2R , TPM4 , and TUBB1 , and classified them according to current guidelines. Apart from seven variants of uncertain significance in 11% of patients, nine variants were classified as likely pathogenic or pathogenic providing a molecular diagnosis for 26% of patients. This report also emphasizes on potentials and pitfalls of this tool and prospectively proposes its rational implementation within the diagnostic algorithms of IPD.


Clinical feasibility of ultrafast intracranial vessel imaging with non-Cartesian spiral 3D time-of-flight MR angiography at 1.5T: An intra-individual comparison study.
Non-Cartesian Spiral readout can be implemented in 3D Time-of-flight (TOF) MR angiography (MRA) with short acquisition times. In this intra-individual comparison study we evaluated the clinical feasibility of Spiral TOF MRA in comparison with compressed sensing accelerated TOF MRA at 1.5T for intracranial vessel imaging as it has yet to be determined. Forty-four consecutive patients with suspected intracranial vascular disease were imaged with two Spiral 3D TOFs (Spiral, 0.82x0.82x1.2 mm3, 01:32 min; Spiral 0.8, 0.8x0.8x0.8 mm3, 02:12 min) and a Compressed SENSE accelerated 3D TOF (CS 3.5, 0.82x0.82x1.2 mm3, 03:06 min) at 1.5T. Two neuroradiologists assessed qualitative (visualization of central and peripheral vessels) and quantitative image quality (Contrast Ratio, CR) and performed lesion and variation assessment for all three TOFs in each patient. After the rating process, the readers were questioned and representative cases were reinspected in a non-blinded fashion. For statistical analysis, the Friedman and Nemenyi post-hoc test, Kendall W tests, repeated measure ANOVA and weighted Cohen's Kappa tests were used. The Spiral and Spiral 0.8 outperformed the CS 3.5 in terms of peripheral image quality (p<0.001) and performed equally well in terms of central image quality (p>0.05). The readers noted slight differences in the appearance of maximum intensity projection images. A good to high degree of interstudy agreement between the three TOFs was observed for lesion and variation assessment (W = 0.638, p<0.001 -W = 1, p<0.001). CR values did not differ significantly between the three TOFs (p = 0.534). Interreader agreement ranged from good (K = 0.638) to excellent (K = 1). Compared to the CS 3.5, both the Spiral and Spiral 0.8 exhibited comparable or better image quality and comparable diagnostic performance at much shorter acquisition times.


Diagnostic clinical parasitology: I. Proper specimen collection and processing.
This article (first of a series of four papers on diagnostic clinical parasitology) presents various collection methods and diagnostic procedures which are available for laboratory diagnosis of human parasitic infections. The information presented includes the pros and cons of each method discussed. When a laboratory selects various procedures, this decision should be based on a thorough understanding of the value and limitations of each technique selected. The topics to be included in the next three presentations include: protozoa, helminths, and blood parasites.


Exploring the impact of mindfulness meditation training in pre-licensure and post graduate nurses.
The complex, high stress, technologically laden healthcare environment compromises providers' ability to be fully present in the moment; especially during patient interactions. This "pulling away" of attention (mindlessness) from the present moment creates an environment where decision making can take place in the absence of thoughtful, deliberate engagement in the task at hand. Mindfulness, can be cultivated through a variety of mindfulness practices. Few schools of nursing or hospitals offer mindfulness training, despite study findings supporting its effectiveness in improving levels of mindfulness, and perceived connections with patients and families. A mindfulness program developed for this study and tailored to nursing was used to provide the mindfulness training. Pre and post training assessments were completed and included administration of the Freiburg Mindfulness Inventory (FMI) and the Defining Issues Test (DIT) of moral judgment version 2. A statistically significant improvement in the FMI scores p=0.003 was found. The pre-licensure group did not show a statistically significant improvement in their FMI scores pre to post training (p=0.281), however the post graduate group did (p=0.004). Statistically significant pre - post scores were found in two schemas of the DIT-2 (P [Post conventional] score, p=0.039 and N2 [Maintaining norms] score, p=0.032). Mindfulness training improves mindfulness and some aspects of ethical decision making in the groups studied as part of this project. The findings of this study are promising and further demonstrate the merits of a mindfulness practice, however aspects of mindfulness training would need to be addressed prior to launching a full scale attempt to incorporate this into a work life or some other quality improvement program.


Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation.
We report on the cytogenetic and molecular analysis of a malignant melanoma of the soft parts (MMSP). A t(12;22)(q13;q12) was found as the only structural chromosomal change, and this provides additional support for the important role of this translocation in MMSP development. Molecular analysis revealed in frame fusion between exon 10 of the Ewing's sarcoma oncogene (EWS) and codon 110 of ATF-1. In previously analyzed MMSPs, junctions were observed between EWS exon 8 and ATF-1 codon 65. The present data thus indicate that, as in Ewing's sarcoma, different fusion proteins can occur in MMSP. The presence of the EWS/ATF-1 fusion gene in the tumor cells was demonstrated by dual color fluorescence in situ hybridization on interphase nuclei. Our data provide additional support for the specific association of the t(12;22) and the resulting EWS/ATF-1 gene fusion in MMSP. This particular genetic aberration, therefore, serves as a strong diagnostic marker for MMSP. We conclude that detection of the t(12;22) by cytogenetic or molecular analysis is useful in establishing or confirming the diagnosis of MMSP.


Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway.
Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheally administered with 0.125 mg/kg BLM, 8 mg/kg/day rhTRX was intravenously administered on days 3-6 using one of three protocols: daily bolus injection, 3 h daily infusion or continuous infusion for 96 h. Only the continuous-infusion of rhTRX significantly reduced the neutrophil infiltration compared with the other two methods. The BLM-induced down-regulation of L-selectin expression on circulating neutrophils was inhibited by rhTRX. Oxidized rhTRX showed a comparable effect with reduced rhTRX and rhTRX incubated with plasma or circulating in plasma was more than 99% oxidized. These results suggest that rhTRX becomes oxidized in circulation and continuous infusion of rhTRX suppresses neutrophil recruitment in the airway.


2-Aminoethanol Extraction as a Method for Purifying Sc3N@C80 and for Differentiating Classes of Endohedral Fullerenes on the Basis of Reactivity.
Extraction with 2-aminoethanol is an inexpensive method for removing empty cage fullerenes from the soluble extract from electric-arc-generated fullerene soot that contains endohedral metallofullerenes of the type Sc3N@C2n (n = 34, 39, 40). Our method of separation exploits the fact that C60, C70, and other larger, empty cage fullerenes are more susceptible to nucleophilic attack than endohedral fullerenes and that these adducts can be readily extracted into 2-aminoethanol. This methodology has also been employed to examine the reactivity of the mixture of soluble endohedral fullerenes that result from doping graphite rods used in the Krätschmer-Huffman electric-arc generator with the oxides of Y, Lu, Dy, Tb, and Gd. For example, with Y2O3, we were able to detect by mass spectrometry several new families of endohedral fullerenes, namely Y3C108 to Y3C126, Y3C107 to Y3C125, Y4C128 to Y4C146, that resisted reactivity with 2-aminoethanol more than the empty cage fullerenes and the mono- and dimetallo fullerenes. The discovery of the family Y3C107 to Y3C125 with odd numbers of carbon atoms is remarkable, since fullerene cages must involve even numbers of carbon atoms. The newly discovered families of endohedral fullerenes with the composition M4C2n (M = Y, Lu, Dy, Tb, and Gd) are unusually resistant to reaction with 2-aminoethanol. Additionally, the individual endohedrals, Y3C112 and M3C102 (M = Lu, Dy, Tb and Gd), were remarkably less reactive toward 2-aminoethanol.


[A case of gastric cancer with multiple liver metastases responding to TS-1].
We report the case of a 58-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases, which responded to chemotherapy using TS-1. The patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks rest as 1 cycle. After 4 cycles, most of the liver metastases had disappeared and serum CEA level was reduced from 140 to 53.9. The patient received chemotherapy at our outpatient clinic for 9 months during which time there was no regrowth after the first treatment. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of advanced gastric cancer.


Prevalence of hypertension and its risk factors among cotton textile workers in low- and middle-income countries: a protocol for a systematic review.
Cotton workers are exposed to various hazards in the textile industry that might result in different ailments including hypertension (HTN). However, few attempts have been made to systematically review the prevalence of hypertension and its risk factor among cotton textile workers in low-and middle-income countries (LMICs). The objective of this study will be to evaluate the prevalence of hypertension and its risk factors among adult cotton textile workers in low- and middle-income countries. We designed and registered a study protocol for a systematic review of descriptive epidemiology data. We will include observational studies (e.g., cross-sectional, cohort, surveys) on the epidemiology of hypertension among adult cotton textile workers in low- and middle-income countries. The primary outcome will be the prevalence of hypertension. Secondary outcomes will be the prevalence of risk factors of hypertension. Literature searches will be conducted in multiple electronic databases (from January 2000 onwards), including PubMed/MEDLINE, CINAHL, Science Direct, and Cochrane Library. Gray literature will be identified through searching conference abstracts, thesis dissertations, and public repositories. Two investigators will independently screen all citations, full-text articles, and abstract data. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, gender, years of service, textile department). This systematic review will identify, evaluate, and integrate evidence on the prevalence and risk factors of hypertension among adult cotton textile workers in low- and middle-income countries. Our findings will be made publicly available in a repository and published in a peer-reviewed journal. PROSPERO CRD42020167175.


Development and Implementation of a Real-time Bundle-adherence Dashboard for Central Line-associated Bloodstream Infections.
Central line-associated bloodstream infections (CLABSIs) are the most common hospital-acquired infection in pediatric patients. High adherence to the CLABSI bundle mitigates CLABSIs. At our institution, there did not exist a hospital-wide system to measure bundle-adherence. We developed an electronic dashboard to monitor CLABSI bundle-adherence across the hospital and in real time. Institutional stakeholders and areas of opportunity were identified through interviews and data analyses. We created a data pipeline to pull adherence data from twice-daily bundle checks and populate a dashboard in the electronic health record. The dashboard was developed to allow visualization of overall and individual element bundle-adherence across units. Monthly dashboard accesses and element-level bundle-adherence were recorded, and the nursing staff's feedback about the dashboard was obtained. Following deployment in September 2018, the dashboard was primarily accessed by quality improvement, clinical effectiveness and analytics, and infection prevention and control. Quality improvement and infection prevention and control specialists presented dashboard data at improvement meetings to inform unit-level accountability initiatives. All-element adherence across the hospital increased from 25% in September 2018 to 44% in December 2019, and average adherence to each bundle element increased between 2018 and 2019. CLABSI bundle-adherence, overall and by element, increased across the hospital following the deployment of a real-time electronic data dashboard. The dashboard enabled population-level surveillance of CLABSI bundle-adherence that informed bundle accountability initiatives. Data transparency enabled by electronic dashboards promises to be a useful tool for infectious disease control.


Strangulating bowel obstruction due to a small intestinal knot in a case of parastomal hernia.
An intestinal knot is a rare cause of intestinal obstruction. We report a rare case of strangulating bowel obstruction due to a small intestinal knot. A 69-year-old man who had an end colostomy was admitted with severe abdominal pain and vomiting. Contrast enhancement computed tomography showed dilated intestinal loops with decreased contrast enhancement in the parastomal hernia sac. Emergent laparotomy revealed a dilated and congested intestinal loop strangulated by a small intestinal knot. The knot was carefully untied, and the color of the intestinal loop improved subsequently. Intestinal resection was not performed. Immediate diagnosis and prompt surgical treatment are crucial for strangulating small bowel obstruction due to an intestinal knot. A high degree of clinical suspicion of an intestinal knot is needed in patients with a large extra-abdominal cavity.


Investigation of the 4,000-Hertz dip by detailed audiometry.
It is well known that a 4,000-Hz dip is often observed in the initial stage of noise-induced hearing loss and acoustic trauma, but it does not always occur as a result of these causes, and quite often the cause is unknown. Pure tone audiograms of 159 patients (76 cases of noise-induced hearing loss, 62 cases of hearing loss of unknown cause, 21 cases of familial hearing loss) with a 4,000-Hz dip were studied by detailed audiometry to clarify this configuration. The types of dip were classified into 11 groups; however, the basic types are the cone type, bowl type, and dish type, which show the smooth line of the hearing threshold. There were no clear differences in dip configuration among the 3 causes of hearing loss. It was thought that the dips displayed similar configurations regardless of the cause.


Emergency presentation of emboli to multiple sites from an atrial myxoma.
A middle aged man presented to our ED with back pain and confusion, had evidence of acute arterial insufficiency to his lower limbs and myocardial infarction on initial ECG. His workup included an urgent CT, which revealed a filling defect in his dilated left atrium, renal and splenic infarcts, and an embolism in his left internal iliac artery. Urgent embolectomy and fasciotomy could not save his left lower limb, and emergency cardiac surgery was required to excise an atrial myxoma. A brief narrative review of the literature is also presented, with this case being unusual in causing such widespread concurrent multiple organ damage, including stroke and myocardial infarct.


Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle.
Although previous studies demonstrated beneficial effects of estrogen on cardiovascular function, the Women's Health Initiative has reported an increased incidence of coronary heart disease and stroke in postmenopausal women taking hormone replacement therapy. The objective of the present study was to identify a molecular mechanism whereby estrogen, a vasodilatory hormone, could possibly increase the risk of cardiovascular disease. Isometric contractile force recordings were performed on endothelium-denuded porcine coronary arteries, whereas molecular and fluorescence studies identified estrogen signaling molecules in coronary smooth muscle. Estrogen (1-1,000 nM) relaxed arteries in an endothelium-independent fashion; however, when arteries were pretreated with agents to uncouple nitric oxide (NO) production from NO synthase (NOS), estrogen contracted coronary arteries with an EC(50) of 7.3 +/- 4 nM. Estrogen-induced contraction was attenuated by reducing superoxide (O(2)(-)). Estrogen-stimulated O(2)(-) production was detected in NOS-uncoupled coronary myocytes. Interestingly, only the type 1 neuronal NOS isoform (nNOS) was detected in myocytes, making this protein a likely target mediating both estrogen-induced relaxation and contraction of endothelium-denuded coronary arteries. Estrogen-induced contraction was completely inhibited by 1 muM nifedipine or 10 muM indomethacin, indicating involvement of dihydropyridine-sensitive calcium channels and contractile prostaglandins. We propose that a single molecular mechanism can mediate the dual and opposite effect of estrogen on coronary arteries: by stimulating type 1 nNOS in coronary arteries, estrogen produces either vasodilation via NO or vasoconstriction via O(2)(-).


[Neurohumoral effect of the dopaminergic system on development of alimentary-constitutional obesity].
Decrease in quantity and activity of dopamine receptors at patients with obesity is established. This leads to overeating, and abnormal weight gain. The article presents data on the impact of the dopaminergic system in the levels of leptin, prolactin, insulin, and the development of alimentary-constitutional obesity in these patients.


NiII(TPA) as an efficient catalyst for alkane hydroxylation with m-CPBA.
A simple Ni(II)(TPA) complex [TPA = tris(2-pyridylmethyl)amine] has been demonstrated to act as an efficient turnover catalyst for alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid), in which contribution of a NiO(+) (nickel-oxo) type active oxygen species is suggested.


Regional use of the Australian Chronic Disease Dental Scheme.
To determine whether a different number and type of services were provided in Australian regional areas under the Australian Government-funded Chronic Disease Dental Scheme (CDDS). Retrospective analysis of administrative payments data. Australia. Patients receiving dental services under the Medicare CDDS. The CDDS. Number and type of services. CDDS service categories Australian Statistical Geography Standard (ASGS) regions were collected by the Australian Department of Human Services between 2008 and 2013 and compared by Australian Bureau of Statistics ASGS estimated resident regional 2011 population, and by employed number of dentists, dental specialists and dental prosthetists from the 2011 National Health Workforce Dataset. Number of services provided was greatest in major cities (79.0%), followed by inner regional (15.4%), outer regional (5.2%) and remote/very remote Australia (0.4%). Number of services per head of population decreased from 1.088 in major cities to 0.16 in remote/very remote areas. Number of services provided per dental practitioner showed minimal variation between major city (1672), inner (1777) and outer regional (1627) areas, but was lower in remote/very remote areas (641). Crown and bridge, periodontic, endodontic and removable prostheses per dental practitioner were most frequently supplied in the major cities, but restorative care and oral surgery were more frequently supplied in inner and outer regional areas. The number of CDDS services provided declined with regional remoteness. There was a marked difference in the utilisation of the scheme between major cities and remote/very remote areas in both number and type of service levels.


Diabetes-associated endometrial disruption in the Chinese hamster: structural changes in relation to progressive hyperglycemia.
The relationship between progressive diabetes and endometrial structure was examined in genetically diabetic Chinese hamsters. Uterine samples were collected from animals exhibiting prediabetic to overt diabetic conditions and from matched control animals. In controls (with blood glucose levels less than or equal to 145 mg/dl) the endometrium was typified by an intact luminal epithelium, a thin underlying basement membrane and a well-organized stroma layer. In contrast, mildly diabetic (150-250 mg/dl) animals exhibited a compressed luminal epithelium which was embedded in a thickened basement membrane infiltrated with phagocytic blood elements. The stromal layer contained several irregular cells which were characterized by cytoplasmic vacuolization and collagen fiber separation by an amyloid-like, intercellular ground substance. In overt diabetic animals (greater than or equal to 300-500 mg/dl), the luminal epithelial cells were located over a greatly thickened basement membranes which was infiltrated by phagocytic blood elements and degenerating stromal cell membranes. The lumens of the glands were closed and the stromal cells were separated by an increased intercellular space occupied by an amyloid-like ground substance. Many stromal cells exhibited cytoplasmic vacuolization. These studies demonstrate that uterine involution associated with diabetes occurs in a sequential manner and is temporally related to progressive elevations in blood glucose levels.


[Effects of nitrogen form on growth and quality of Chrysanthemums morifolium].
This paper is aimed to study the effects of nitrogen form on the growth and quality of Chrysanthemums morifolium at the same nitrogen level. In order to provide references for nutrition regulation of Ch. morifolium in field production, pot experiments were carried out in the greenhouse at experimental station of Nanjing Agricultural University. Five proportions of ammonium and nitrate nitrogen were set up and a randomized block design was applied four times repeatedly. The results showed that the growth and quality of Ch. morifolium were significantly influenced by the nitrogen form. The content of chlorophyll and photosynthesis rate were the highest at the NH4(+) -N /NO3(-) -N ratio of 25:75; The activities of NR in different parts of Ch. -morifolium reached the highest at the NH4(+) - N/NO3(-) -N ratio of 0: 100. The contents of nitrate nitrogen in the root and leaves reached the highest at the NH4(+) -N/NO3(-) -N ratio of 50:50. The activities of GS, GOGAT and the content of amylum increased with the ratio of NO3(-) -N decreasing and reached it's maximum at the NH4 + -N/NO3 - -N ratio of 100: 0. The content of ammonium nitrogen were the highest at the NH4 + -N /NO3 --N ratio of 75: 25, while the content of soluble sugar reached the highest at the NH4(+)-N/NO3(-) -N ratio of 25: 75. The content of flavones, chlorogenic acid and 3,5-O-dicoffeoylqunic acid were 57.2 mg x g(-1), 0.673% and 1.838% respectively, reaching the maximum at the NH4(+) -N /NO3(-) -N ratio of 25:75; The content of luteoloside increased with the ratio of NO3(-) -N increasing and reached it's maximum at the NH4(+) -N/NO3(-) -N ratio of 0: 100. The yield of Ch. morifolium reached it's maximum at the NH4(+) -N /NO3(-) -N ratio of 25:75. Nitrogen form has some remarkable influence on the nitrogen metabolism, photosynthesis and growth, Nitrogen form conducive to the growth and quality of Ch. morifolium at the NH4(+) -N /NO3(-) -N ratio of 25: 75.


Effectiveness of contextual education for self-management in Thai Muslims with type 2 diabetes mellitus during Ramadan.
Fasting in Ramadan has adverse effects on health of Muslims with diabetes. Key strategies to prepare the patients are to provide appropriate health education to the patients prior to Ramadan and to adjust anti-diabetic medicines during Ramadan. To study outcomes of the specific health care services that providing health education in parallel with counseling by Islamic leader The Thai Muslims with type 2 diabetes mellitus were divided into two groups. There were 62patients in experimental group that was provided with specific health care service for Thai Muslims with diabetes in which health education prior to Ramadan and adjustment ofanti-diabetic medicine applied. The other was control group with 28patients that was provided only with original health care service. The results were monitored after Ramadan by interviews, weight and waist measurements, blood pressure measurement and blood tests. Both mean systolic and diastolic blood pressure were well controlled in both groups and slightly decreased after Ramnadan. The mean diastolic blood pressure of the experimental group decreased after Ramadan (p-value = 0.041). From behavior point of view, it was found that the patients in the experimental group had consumed less sweetenedfood (p-value = 0.002). There was no incidence ofsevere hypoglycemia in either experimental or control group. The number and portion of patients with hypoglycemic symptoms in experimental group were lower than those in controlled group (p-value = 0.013). Specific health care service by providing health education prior to Ramadan and adjustment ofanti-diabetic medicine application resulted in a positive effect as the patients tended to consume less sweetenedfood to keep blood sugar level in control. Fasting could affect the patients 'health in apositive way as it helps to control blood pressure, while in parallel, adjustment of anti-diabetic medicine application helps to prevent hypoglycemia. This health care service, which can be achieved in collaboration with a health care team and Islamic leaders, is useful and suitable for Thai Muslims with diabetes mellitus type 2.


Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC-QqQ MS Combined with Chemometrics.
Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, this remains underexplored for Wuyi Rock tea cultivars. In this study, we investigated the leaf metabolite profiles of 14 major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF MS and UPLC-QqQ MS with data processing via principal component analysis and cluster analysis. Relative quantitation of 49 major metabolites including flavan-3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino acids revealed clear variations between tea cultivars. In particular, catechins, kaempferol and quercetin derivatives were key metabolites responsible for cultivar discrimination. Information on the varietal differences in the levels of bioactive/functional metabolites, such as methylated catechins, flavonol glycosides and theanine, offers valuable insights to further explore the nutritional values and sensory qualities of Wuyi Rock tea. It also provides potential markers for tea plant fingerprinting and cultivar identification.


Effects of Lumbar Strengthening Exercise in Lower-Limb Amputees With Chronic Low Back Pain.
To analyze the effect of lumbar strengthening exercise in lower-limb amputees with chronic low back pain. We included in this prospective study 19 lower-limb amputees who had experienced low back pain for longer than 6 months. Participants were treated with 30-minute lumbar strengthening exercises, twice weekly, for 8 weeks. We used the visual analog scale (VAS), and Oswestry low back pain disability questionnaire, and measured parameters such as iliopsoas length, abdominal muscle strength, back extensor strength, and back extensor endurance. In addition, we assessed the isometric peak torque and total work of the trunk flexors and extensors using isokinetic dynamometer. The pre- and post-exercise measurements were compared. Compared with the baseline, abdominal muscle strength (from 4.4±0.7 to 4.8±0.6), back extensor strength (from 2.6±0.6 to 3.5±1.2), and back extensor endurance (from 22.3±10.7 to 46.8±35.1) improved significantly after 8 weeks. The VAS decreased significantly from 4.6±2.2 to 2.6±1.6 after treatment. Furthermore, the peak torque and total work of the trunk flexors and extensors increased significantly (p<0.05). Lumbar strengthening exercise in lower-limb amputees with chronic low back pain resulted in decreased pain and increased lumbar extensor strength. The lumbar strengthening exercise program is very effective for lower-limb amputees with chronic low back pain.


Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson's disease.
Dysfunction of the glymphatic system, an intracranial clearance pathway that drains misfolded proteins, has been implicated in the onset of Parkinson's disease (PD). Recently, the coupling strength of global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics have been suggested to be an indicator of glymphatic function. Using resting-state functional magnetic resonance imaging (MRI), we quantified gBOLD-CSF coupling strength as the cross-correlation between baseline gBOLD and CSF inflow signals to evaluate glymphatic function and its association with the clinical manifestations of PD. We found that gBOLD-CSF coupling in drug-naïve PD patients was significantly weaker than that in normal controls, but significantly stronger in patients less affected by sleep disturbances than in those more affected by sleep disturbances, based on the PD sleep scale. Furthermore, we collected longitudinal data from patients and found that baseline gBOLD-CSF coupling negatively correlated with the rate of change over time, but positively correlated with the rate of change in UPDRS-III scores. In conclusion, severe gBOLD-CSF decoupling in PD patients may reflect longitudinal motor impairment, thereby providing a potential marker of glymphatic dysfunction in PD.


The Surgical Correction of Cavovarus Deformity in Charcot-Marie-Tooth Disease.
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neuropathy. CMT disease is a motor-sensory neuropathy with multiple genotypes. By comparison, the phenotypic expression is more uniform, with two main presentations. Most patients who need surgical care have progressive cavovarus foot deformity, with muscle imbalance causing a nonplantigrade foot, soft-tissue contractures, and abnormal bone morphology. Surgical treatment can be life-changing for these patients, allowing them to walk potentially brace free with more endurance and less pain. Early realignment procedures may reduce progression of joint arthritis. A minority of patients have diffuse paralysis below the knee. These patients are best treated with ground-reaction ankle-foot orthoses. This review article is based on the senior author's extensive experience with CMT, along with the limited evidenced-based literature.


Mometasone furoate ointment and cream 0.1 percent in treatment of psoriasis: comparison with ointment and cream formulations of fluocinolone acetonide 0.025 percent and triamcinolone acetonide 0.1 percent.
Mometasone furoate (Elocon) is a newly formulated and unique medium-potency synthetic 17-heterocyclic corticosteroid. The efficacy and safety of the ointment and cream formulations (0.1 percent) of the corticosteroid, administered once daily, were compared with those of the ointment and cream formulations of fluocinolone acetonide 0.025 percent administered three times daily and triamcinolone acetonide 0.1 percent administered twice daily in four multicenter clinical studies. They were conducted involving psoriasis patients with chronic and moderate to severe disease. Evaluation of change in disease sign scores indicated that mometasone ointment, applied once daily, was significantly more effective (P less than 0.01) than fluocinolone ointment, applied three times daily, and triamcinolone ointment, applied twice daily. The cream formulation of mometasone was significantly more effective (p less than 0.001) than fluocinolone cream, applied three times daily, and equivalent to triamcinolone cream, applied twice daily. The incidence of local adverse experiences following treatment with the ointment or cream formulations of mometasone was minimal. Mometasone ointment and cream provide a highly effective once-a-day treatment for moderate to severe psoriasis with minimal risk of side effects.


Workload in Norwegian general practice 2018 - an observational study.
Rising workload in general practice has been a recent cause for concern in several countries; this is also the case in Norway. Long working hours and heavy workload seem to affect recruitment and retention of regular general practitioners (RGPs). We investigated Norwegian RGPs' workload in terms of time used on patient-related office work, administrative work, municipality tasks and other professional activities in relation to RGPs, and gender, age, employment status and size of municipality. In early 2018, an electronic survey was sent to all 4716 RGPs in Norway. In addition to demographic background, the RGP reported minutes per day used on various tasks in the RGP practice prospectively during 1 week. Working time also included additional tasks in the municipality, other professional work and on out-of-hours primary health care. Differences were analysed by chi square test, independent t-tests, and one-way ANOVA. Among 1876 RGPs (39.8%), the mean total working hours per week was 55.6, while the mean for regular number of working hours was 49.0 h weekly. Men worked 1.5 h more than women (49.7 vs. 48.2 h, p = 0.010). Self-employed RGPs work more than salaried RGPs (49.3 vs. 42.5 h, p < 0.001), and RGPs age 55-64 years worked more than RGPs at age 30-39 (51.1 vs. 47.3 h, p < 0.001). 54.1% of the regular working hours was used on face-to-face patient work. Norwegian RGPs have long working hours compared to recommended regular working hours in Norway, with small gender differences. Only half of the working time is used on face-to-face consultations. There seems to be a trend of increasing workload among Norwegian GPs, at the cost of direct patient contact. Further research should address identifying factors that can reduce long working hours.


Early diagnosis of bone biopsies--the role of sediment cytology.
This study analyses the role of the cytological examination of the sediment of the formalin in which bone biopsy specimens are received, in the early diagnosis of bone lesions. Of the one hundred lesions studied using this technique, twenty six of thirty three malignant lesions (seventy nine percent) could be diagnosed as malignant when relevant clinical and radiological data were considered. Sixty six benign lesions yielded sparsely cellular smears with benign cell. There was one false positive for malignancy. This simple rapid diagnostic technique can be used to advantage in the early diagnosis, and treatment planning of bone lesions.


Is there a need for improved pharmacy services to the operating theatre?
A study to assess the control and handling of drugs within an operating theatre complex (10 theatres) of an 850-bed hospital, has revealed the presence of unusable medication and thus highlighted the need for improved pharmacy services. The aims and objectives of the pharmacy department to enhance such services included improvement of drug control of stock medication and the introduction of clinical pharmacy services within the operating theatre. To undertake this, three systems were evaluated with reference to systems already in use in the U.S.A. Operating theatre visits by a clinical pharmacist, coupled with the expansion of the existing drug distribution service, were identified as the most cost-effective methods that would allow the objectives to be met. Consequently, this has now been implemented within the operating theatre complex.


Cesarean scar endometriosis: presentation of 198 cases and literature review.
Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.


Asthma and influenza virus infection:focusing on cell death and stress pathways in influenza virus replication.
Asthma is one of the fastest growing syndromes in many countries and is adding a huge cost to the health care system. Increasing reports have linked airway infectious diseases to asthma. Influenza is one of the most serious airway infectious diseases and in recent years there have been some serious influenza virus pandemics which caused increased fatality in numerous different populations. Diverse host response pathways during virus infection have been identified, including different cell death and survival pathways. These pathways include 1) programmed cell death I (apoptosis), 2) programmed cell death II (autophagy), and 3) endoplasmic reticulum stress with subsequent unfolded protein response (UPR). There has been extensive research on the regulatory roles of these pathways during the influenza virus life cycle. These studies address the benefits of enhancing or inhibiting these pathways on viral replication. Here we review the most recent and significant knowledge in this area for possible benefits to clinicians and basic scientist researchers in different areas of the respiratory and virology sciences.


Blocking of rat hippocampal Cx36 by quinine accelerates kindling epileptogenesis.
There are abundant studies indicating that blocking gap junctions (GJs) containing connexin 36 (Cx36) inhibit seizures. However, recent evidences demonstrate proconvulsant effect of such intervention. Electrical coupling between GABAergic interneurons in CA1 region of hippocampus is mediated through Cx36 GJs. We investigated effect of quinine, a specific blocker of Cx36, on the seizure severity and epileptogenesis in amygala kindling model of epilepsy in rats. Quinine (1, 50, 100, 500 and 2000 µM/rat) was injected directly into the CA1 and kindled seizure parameters including behavioral seizure stage, duration of evoked afterdischarges, and duration of generalized seizures behavior were recorded 10 min afterward. Moreover, quinine (1, 30, and 100 µM/rat) was injected intra CA1 once daily during kindling development. At the doses used, quinine had no significant effect on amygdala-kindled seizures. However, quinine 100 µM significantly accelerated kindling rate. Blockade of Cx36 GJs coupling and consequent disruption of inhibitory transmission in GABAergic interneurons in CA1 area seems to be responsible for the antiepileptogenic effect of quinine.


A human-oriented framework for developing assistive service robots.
Multipurpose robots that can perform a range of useful tasks have the potential to increase the quality of life for many people living with disabilities. Owing to factors such as high system complexity, as-yet unresolved research questions and current technology limitations, there is a need for effective strategies to coordinate the development process. Integrating established methodologies based on human-centred design and universal design, a framework was formulated to coordinate the robot design process over successive iterations of prototype development. An account is given of how the framework was practically applied to the problem of developing a personal service robot. Application of the framework led to the formation of several design goals which addressed a wide range of identified user needs. The resultant prototype solution, which consisted of several component elements, succeeded in demonstrating the performance stipulated by all of the proposed metrics. Application of the framework resulted in the development of a complex prototype that addressed many aspects of the functional and usability requirements of a personal service robot. Following the process led to several important insights which directly benefit the development of subsequent prototypes. Implications for Rehabilitation This research shows how universal design might be used to formulate usability requirements for assistive service robots. A framework is presented that guides the process of designing service robots in a human-centred way. Through practical application of the framework, a prototype robot system that addressed a range of identified user needs was developed.


Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.
We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH abuse liability, contemporary "designer drug," pertinence to the newer transdermal and chiral switch MPH formulations, as well as problematic internal standard. d-EPH selectively targets the dopamine transporter, whereas d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol coabuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: an otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; a substimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; ethanol elevates blood, brain, and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder.


Correlation between Traditional Chinese Medicine Syndromes and Type 2 Myocardial Infarction in Critically Ill Patients with Pulmonary Disease.
Treatment based on syndrome differentiation under the traditional Chinese medicine (TCM) framework has been shown to be helpful in patients with coronary artery disease. We hypothesized that syndrome types could predict the risk of type 2 myocardial infarction (T2MI) caused by imbalance between myocardial oxygen supply and demand in critically ill patients with pulmonary disease. This retrospective study included consecutive critically ill patients with pulmonary disease admitted to the ICU at Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 1, 2017, to July 1, 2019. Diagnosis of T2MI was based on the fourth universal definition of myocardial infarction. Risk factors associated with T2MI were identified using multivariate regression analysis. A total of 244 patients were included in the study: 78 who developed T2MI and the remaining 166 who did not develop T2MI during hospitalization. The incidence of phlegm syndrome and deficiency syndrome was 61.9% and 38.1%, respectively. In comparison with the patients with phlegm syndrome, the incidence of T2MI in patients with deficiency syndrome is significantly higher (40.9% vs. 26.5%, P=0.019). In multivariate logistic regression, T2MI was independently associated with the baseline troponin level (OR 12.682, 95% CI 1.397∼115.121; P=0.024), hemoglobin < 55 g/L (OR 12.76, 95% CI 2.359∼69.021; P=0.003), mechanical ventilation (OR 2.244, 95% CI 1.029∼4.892; P=0.042), and TCM deficiency syndrome (OR 2.214, 95% CI 1.032∼4.749; P=0.041). After adjusting for confounding factors in Cox regression models, the hazard ratio (95% confidence interval) of qi deficiency syndrome groups was 1.183 (95% CI 1.053∼3.123, P=0.032). Patients with deficiency syndrome are at high risk of T2MI, especially those combined with qi deficiency syndrome.


Safety of consumer handling of fresh produce from the time of purchase to the plate: a comprehensive consumer survey.
A national mail survey focusing on consumer handling of fresh fruits and vegetables was conducted among 2,000 randomly selected households in the United States. The objective was to quantify consumer practices relating to the purchase, transport, storage, and preparation of fresh produce, with emphasis on practices that affect safety. Following an additional mailing procedure, a response rate of 33% was obtained. Six percent of the consumers responded that they seldom or never wash fresh produce, and more than 35% indicated that they do not wash their melons before preparation. Twenty-three percent of the respondents indicated placing their meat, poultry, and fish on a refrigerator shelf above other foods, and 9% do not place their produce at any specific location in the refrigerator. Almost half of the respondents indicated not always washing their hands before handling fresh produce. Ninety-seven percent of respondents reported that they always wash their food preparation surfaces after contact with meat products, yet 5% and 24% dry wipe or wash with water only, respectively. The results from this study suggest that women, lower-income households, people 65 years and older, and non-college graduates practice safer food handling methods than men, higher-income households, people younger than 65 years, and college or postcollege graduates. The survey findings suggest that consumer education materials should emphasize safe handling practices from purchase through consumption. Educational outreach should target specific subpopulations, men, college graduates, higher-income households, and people younger than 65 years because of their higher frequency of unsafe handling and washing practices.


Access to chiral γ-butenolides via palladium-catalyzed asymmetric allylic C-H alkylation of 1,4-dienes.
Asymmetric allylic C-H alkylation of 1,4-pentadienes with α-angelica lactones has been developed by tri-axial phosphoramidite-palladium catalysis. This reaction can tolerate a range of functional groups under mild conditions, furnishing versatile chiral γ,γ-disubstituted butenolides in high yields with good to high levels of stereoselectivity.


[The influence of teaching and hygienic procedures on the state of denture area in patients using frame dentures (temporary information)].
Basing on clinical observations the authors present the influence of teaching and hygienic procedures on the state of denture bearing area in patients using frame dentures. The paper is based on 150 cases and it forms one of the stages of long-term clinical procedures performed during prosthetic treatment.


Transient loss of power of accommodation in 1 eye following inferior alveolar nerve block: report of 2 cases.
Unintended intravascular injection from inferior alveolar nerve blocks can result in frustrating distant complications affecting such structures as the middle ear and eyes. Possible complications affecting the eyes include blurring of vision, diplopia, mydriasis, palpebral ptosis and amaurosis (temporary or permanent). In this article, we present a complication that has been reported only rarely. Two patients developed transient loss of power of accommodation of the eye resulting in blurred vision after routine inferior alveolar nerve blocks on the ipsilateral side. Clear vision returned within 10-15 minutes after completion of the blocks. The possible explanation for this phenomenon is accidental injection into the neurovascular bundle of local anesthetic agents, which were carried via the blood to the orbital region. This resulted in paralysis of a branch of cranial nerve III, the short ciliary nerves that innervate the ciliary muscle, which controls accommodation.


Preparation of Dual-Emitting Ln@UiO-66-Hybrid Films via Electrophoretic Deposition for Ratiometric Temperature Sensing.
Engineering novel dual-emitting metal-organic frameworks (MOFs) with wide emission ranges for application as ratiometric temperature sensors is still a challenge. In this paper, two novel dual-emitting MOFs with intergrated lanthanide metals and luminescent ligand in a UiO-66-type structure, named Ln@UiO-66-Hybrid, were prepared via the combination of postsynthetic modification and postsynthetic exchange methods. Subsequently, the as-synthesized MOFs were deposited onto fluorine tin oxide substrates through electrophoretic deposition by taking advantage of the charges from the unmodified carboxylic groups of the MOFs. The as-prepared Tb@UiO-66-Hybrid and Eu@UiO-66-Hybrid films were applied to detect temperature changes. The resulting Tb@UiO-66-Hybrid film exhibited good temperature-sensing properties with a relative sensitivity of up to 2.76% K-1 in the temperature range of 303-353 K. In addition, the Eu@UiO-66-Hybrid film showed excellent temperature-sensing performance based on the energy transfer between the luminescent ligand (H2NDC) and europium ions with a relative sensitivity of up to 4.26% K-1 in the temperature range of 303-403 K.


Enrolled nurse trainees in acute care.
Enrolled nurses (ENs) play a pivotal role in the health workforce in Australia and the role is expanding in many practice settings. An EN traineeship was introduced in an acute medical/surgical setting at St Vincents & Mercy Private Hospital (STVMPH) a large metropolitan private hospital in Victoria, in 2005. Since then there has been a significant increase in the EN workforce across all clinical areas within the organisation. With consideration of skill mix the current percentage of 18.3% of the nursing workforce is ENs. This review shows the viability of such a program in relation to workforce planning and recruitment. Enrolled nurses are a valuable source in the health care environment. The latest figures indicate there are 230,192 registered nurses (RNs) and 52, 895 ENs (Australian Institute of Health and Welfare, 2010). Enrolled nurses account for approximately 23% of the nursing workforce. The common setting for education (clinical placement) and employment for ENs is aged care. Education and employment of ENs in acute hospital settings is necessary to broaden the skill mix of nursing staff in an acute environment. The acute medical setting encourages ENs to develop and advance their clinical skills to practice acute nursing care within their scope of practice.


Loss of negative feedback control of nuclear factor-kappaB2 activity in lymphocytes leads to fatal lung inflammation.
Proteolytic processing of the nuclear factor (NF)-kappaB2 precursor protein p100 generates the active NF-kappaB2 subunit p52, which in turn transcriptionally up-regulates p100 expression. p100 also functions as an IkappaB molecule capable of repressing p52 activity. The biological significance of this negative feedback control loop has yet to be demonstrated in vivo. Here we show that mice deficient in p100 but with constitutive expression of p52 in lymphocytes developed fatal lung inflammation characterized by diffuse alveolar damage with marked peribronchial fibrosis. In contrast, their littermates with only p100 deficiency or constitutive expression of p52 in lymphocytes developed mild lung inflammation with perivascular lymphocyte infiltration and had a normal life span. The fatal lung inflammation is associated with high-level induction of interferon-gamma and its inducible inflammatory chemokines, suggesting the involvement of a T-helper-1 immune response. These findings demonstrate the physiological relevance of the NF-kappaB2 p100 precursor protein in limiting the potentially detrimental effects of constitutive NF-kappaB2 signaling in lymphocytes.


Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice.
Osmotic pumps continuously deliver compounds at a constant rate into small animals. This article introduces a standard protocol used to induce aortic aneurysms via subcutaneous infusion of angiotensin II (AngII) from implanted osmotic pumps. This protocol includes calculation of AngII amount and dissolution, osmotic pump filling, implantation of osmotic pumps subcutaneously, observation after pump implantation, and harvest of aortas to visualize aortic aneurysms in mice. Subcutaneous infusion of AngII through osmotic pumps following this protocol is a reliable and reproducible technique to induce both abdominal and thoracic aortic aneurysms in mice. Infusion durations range from a few days to several months based on the purpose of the study. AngII 1,000 ng/kg/min is sufficient to provide maximal effects on abdominal aortic aneurysmal formation in male hypercholesterolemic mouse models such as apolipoprotein E deficient or low-density lipoprotein receptor deficient mice. Incidence of abdominal aortic aneurysms induced by AngII infusion via osmotic pumps is 5-10 times lower in female hypercholesterolemic mice and also lower in both genders of normocholesterolemic mice. In contrast, AngII-induced thoracic aortic aneurysms in mice are not hypercholesterolemia or gender-dependent. Importantly, multiple features of this mouse model recapitulate those of human aortic aneurysms.


Characterization of two highly amyloidogenic mutants of transthyretin.
The plasma protein transthyretin (TTR) has the potential to form amyloid under certain conditions. More than 50 different point mutations have been associated with amyloid formation that occurs only in adults. It is not known what structural changes are introduced into the structure of this otherwise stable molecule that results in its aggregation into insoluble amyloid fibrils. On the basis of calculations of the frequency of known mutations over the polypeptide, we have constructed two mutants in the D-strand of the polypeptide. These molecules, containing either a deletion or a substitution at amino acid positions 53-55, were unstable and spontaneously formed aggregates upon storage in TBS (pH 7.6). The precipitates were shown to be amyloid by staining with thioflavin T and Congo Red. Their ultrastructure was very similar to that of amyloid fibrils deposited in the vitreous body of patients with familial amyloidotic polyneuropathy type 1 with an amino acid replacement in position 30 (TTRmet30). Like amyloid isolated from the vitreous body of the eye, the amyloid precipitates generated from the TTR mutants exposed a trypsin cleavage site between amino acid residues 48 and 49, while plasma TTRmet30 isolated from amyloidosis patients as well as wild-type TTR only showed minor trypsin sensitivity. Our data indicate that the mutants we have constructed are similar to amyloid precursors or may share structural properties with intermediates on a pathway leading to amyloid deposits of plasma TTR.


Experimenting with embryos: can philosophy help?
Beyond the well-known ethical issues involved in medical experimentation on human subjects, experimenting with embryos raises unique and particularly hard problems. Besides the psychological obstacles connected with the fear of "playing God" and the awe with which we hold the process of the creation of human beings, there are three philosophical problems which are the main subject of the article: 1. The logical problem of circularity: the morality of experimenting on embryos is dependent on the status of the embryo, which in turn is partly decided by experimentation; 2. The metaphysical problem: experiments are justified by the benefits they bring to human subjects; but it is doubtful whether an early embryo is a "subject" and whether coming into being is a "benefit"; 3. The moral problem: the standard constraint on medical experiments is that they benefit either the individual subject or at least members of a relevantly defined group of patients suffering from the same syndrome. But embryo experimentation is often associated with potential cure to people of a completely different category (like geriatric patients). Finally, the article discusses the limits of the force of philosophical arguments in the formation of actual policies for regulating such practices as experimenting with embryos. The widely-shared fourteen-day limit is shown to be a sound practical compromise despite the difficulties in justifying it philosophically.


Experimental study of treatment effectiveness of the natural drug--Naran S in inflammatory conditions of the oral cavity in animals.
The aim of the study was the evaluation of the action of a new natural drug--Naran S, elaborated in the Department of Inorganic Chemistry of the Medical University of Lublin (patent registration P.332066) in the treatment of inflammatory conditions of the oral cavity mucous membrane. The experiment was conducted on male Wistar rats. Topical inflammation of the gum was induced by injecting a complete Freund adjuvant (AF) (Calbiochem) into the inter-dental papilla of the lower incisors. The material was taken, fixed and stained with hematoxylin and eosin and by the use of the Masson's method after 24 hours, 1, 2, and 4 weeks following the injection time. Morphology of the mucous membrane was examined and it was noticed that in the group treated with Naran S infusion the complete rebuilding of the epithelial strata, collagen fibres took place. The shape of the cells was regular and there occurred the elimination of the tissue fluid in the proper mucous membrane. The results obtained in the study allow to claim that the topically given plant drug thanks to its contents of biologically active substance such as: iridoids, flavonoids, phenol acids, tannins, displays curative activity in the therapy of the inflammatory conditions of the oral cavity mucous membrane.


Aspirin: a neuroprotective agent at high doses?
Aspirin, acetylsalicylic acid, is routinely used in clinics as an analgesic, antipyretic and in the secondary prevention of stroke. These effects are caused by low doses of the drug (0.3-3.6 g/day) through the inhibition of cyclo-oxygenase, the enzyme responsible for prostaglandin synthesis. Higher doses of aspirin (4-6 g/day) are used in the treatment of inflammatory conditions such as rheumatoid arthritis and recent laboratory findings suggest that it could play a role in neuroprotection against glutamate excitotoxicity. This article reviews the possible mechanisms of action of high-dose aspirin in neuroprotection.


Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes.
Asthma is a chronic inflammatory disease of the airways associated with excess production of Th2 cytokines and lung eosinophil accumulation. This inflammatory response persists in spite of steroid administration that blocks autocrine/paracrine loops of inflammatory cytokines, and the detailed mechanisms underlying asthma exacerbation remain unclear. Here, we show that asthma exacerbation is triggered by airway macrophages through a prion-like cell-to-cell transmission of extracellular particulates, including ASC protein, that assemble inflammasomes and mediate IL-1β production. OVA-induced allergic asthma and associated IL-1β production were alleviated in mice with small GTPase Arf6-deficient macrophages. The extracellular ASC specks were slightly engulfed by Arf6-/- macrophages, and the IL-1β production was reduced in Arf6-/- macrophages compared with that in WT macrophages. Furthermore, pharmacological inhibition of the Arf6 guanine nucleotide exchange factor suppressed asthma-like allergic inflammation in OVA-challenged WT mice. Collectively, the Arf6-dependent intercellular transmission of extracellular ASC specks contributes to the amplification of allergic inflammation and subsequent asthma exacerbation.


Epidemiology of Patients with Ovarian Cancer with and Without a BRCA1/2 Mutation.
Ovarian cancer survival rates have improved only slightly in recent decades; however, treatment of this disease is expected to undergo rapid change as strategies incorporating molecular-targeted therapies enter clinical practice. Carriers of deleterious mutations (defined as a harmful mutation) in either the BRCA1 or BRCA2 gene (BRCAm) have a significantly increased risk of developing ovarian cancer. Epidemiology data in large (>500 patients) unselected ovarian cancer populations suggest that the expected incidence rate for BRCAm in this population is 12-14 %. Patients with a BRCAm are typically diagnosed at a younger age than those without a BRCAm. Associations with BRCAm vary according to ethnicity, with women of Ashkenazi Jewish descent being 10 times more likely to have a BRCAm than the general population. In terms of survival, patients with invasive epithelial ovarian cancer who have a BRCAm may have improved overall survival compared with patients who do not carry a BRCAm. Although genetic testing for BRCAm remains relatively uncommon in ovarian cancer patients, testing is becoming cheaper and increasingly accessible; however, this approach is not without numerous social, ethical and policy issues. Current guidelines recommend BRCAm testing in specific ovarian cancer patients only; however, with the emergence of treatments that are targeted at patients with a BRCAm, genetic testing of all patients with high-grade serous ovarian cancer may lead to improved patient outcomes in this patient population. Knowledge of BRCAm status could, therefore, help to inform treatment decisions and identify relatives at increased risk of developing cancer.


Use of a colorimetric carbon dioxide sensor for nasoenteric feeding tube placement in critical care patients compared with clinical methods and radiography.
Misplacement of nasoenteric feeding tubes (NFTs) into the airway instead of the esophagus leads to complications. Healthcare providers have relied on clinical methods, devices such as carbon dioxide (CO(2)) sensors, and radiography (the gold standard) to evaluate NFT placements. Most institutions include radiographs in their protocols for NFT insertions, making it expensive and cumbersome. A new commercial CO(2) sensor was developed to assist in these procedures, and the authors evaluated its use. Nurses performing NFT placement completed questionnaires following each procedure. The nurses recorded the clinical methods used to determine proper insertion and, based on them, where the NFT was located. Nurses then evaluated NFT insertion with the CO(2) sensor; from the readings, they recorded where the tube was located. Confirmation of tube placement was performed radiographically. The authors evaluated 424 NFT insertions. Of these, 15 (3.5%) were incorrectly placed into the airway, and 409 were correctly placed into the esophagus. The CO(2) sensor correctly assessed NFT placement in 421 (99%) of the 424 cases. The authors found the device to have a sensitivity of 86.7% and a specificity of 99.8%. The CO(2) sensor is a helpful bedside tool to use in conjunction with clinical methods during NFT insertions. However, there is insufficient evidence to abandon the use of radiographs to confirm tube placement.


Getting the terminology right in sexual health research: the importance of accurately classifying fuck buddies among men who have sex with men.
The aim of this report was to raise the issue of the definition and classification of partner terminology in men who have sex with men (MSM) research, particularly in regards to 'fuck buddies'. If definitions in research differ from general consensus in the MSM population, it is possible that public health strategies will be ineffective as the target population may be inaccurate. Thirty semistructured interviews with MSM attending the Melbourne Sexual Health Centre were conducted, focusing on the willingness to change sexual practices to reduce the risk of pharyngeal gonorrhoea. As part of these interviews, men were also asked their views on the terminology they used to describe their relationships and sexual partners. The degree of emotional attachment often defined the type or classification of relationships. There was a consensus among men that partners they engaged with for 'sex only' were classified as casual partners and partners with whom there was an emotional attachment or formalisation of the relationship were classified as 'regular partners'. However, the classification of 'fuck buddy' as a regular or casual partner was less clear. Further research is needed to ascertain the ways in which men conceptualise sexual relationships and define or classify partner types, particularly 'fuck buddy' relationships. A third category for sexual relationships should be considered to encapsulate fuck buddy relationships.


Changes in online food access during the COVID-19 pandemic and associations with deprivation: a longitudinal analysis.
Food prepared out-of-home is typically energy dense and nutrient poor. Online food delivery services such as Just Eat and Deliveroo facilitate access to this food. The number of outlets accessible through these services reportedly increased in England during the COVID-19 pandemic, possibly exacerbating inequalities in access to unhealthy food. We investigated changes in online food outlet access, and the extent to which they were socioeconomically patterned throughout the COVID-19 pandemic. In November, 2019, and monthly between June, 2020, and March, 2022, we used automated methods to construct a dataset containing information about all outlets in England registered to accept orders through the company Just Eat. Across 2118 postcode districts, we identified the number of accessible outlets. We used a negative binomial generalised estimating equation to investigate changes in the number of accessible outlets over time, adjusting for population density, the number of food outlets in the physical food environment, and rural urban classifications. We stratified analyses by deprivation quintile (Q). All data were publicly available. Across England, the median number of outlets accessible online decreased from 63·5 (IQR 16·0-156·0) in November, 2019, to 57·0 (11·0-163·0) in March, 2022. However, we observed variation across deprivation quintiles. In March 2022, the median number of outlets accessible online was 175·0 (104·0-292·0) in the most deprived areas (Q5) compared to 27·0 (8·5-60·5) in the least deprived (Q1). In adjusted analyses, we estimated that the number of outlets accessible online in the most deprived areas was 10% higher in March, 2022, compared to November, 2019 (incidence rate ratio [IRR)] 1·10 [1·07-1·13]). By contrast, in the least deprived areas, we estimated a 19% decrease (IRR 0·81 [0·79-0·83]) in food outlets. During the first 2 years of the COVID-19 pandemic, the number of food outlets accessible online increased only in the most deprived areas. We could not determine the extent to which the changes we observed were already underway. Nevertheless, increased online food outlet access might prompt unhealthy food consumption and undermine public health interventions implemented in the physical food environment. Further research could examine changes in the type of food outlets accessible online and through our dataset, seek to understand the extent to which changes in access are associated with changes to food practices, diet quality, and health. National Institute for Health Care Research School for Public Health Research, Medical Research Council.


Left Ventricular Remodelling: A Problem in Search of Solutions.
Cardiac remodelling (REM) is a generally unfavourable process that leads to left ventricular dilation in response to cardiac injury, predominantly acute myocardial infarction (AMI). REM occurs in around 30 % of anterior infarcts despite timely primary coronary intervention and the use of drugs, i.e. angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs), beta-blockers, aldosterone inhibitors and statins. In order to diagnose REM, many imaging modalities (echocardiography, cardiac magnetic resonance, scintigraphy) are employed together with an increasing number of serum biomarkers including microRNAs. The most widely used definition of REM is a >20 % increase in left ventricular end-diastolic volume (LVEDV). There is also evidence that regression of REM can occur, i.e. reverse REM. The latter is defined as a ≥10 % decrease in left ventricular end-systolic volume (LVESV) and confers a more favourable outcome. Many therapeutic agents may be used during primary intervention and over the long term; however, few have demonstrated significant benefits. Revascularisation, anti-REM surgery and, where indicated, cardiac resynchronisation therapy can be of benefit. Gene therapy by sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA-2a) transfer has been investigated but data from the Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2) trial were disappointing. Progenitor cell therapy shows promise. In conclusion, therapy for REM remains inadequate.


A single amino acid substitution strongly modulates the activity and substrate specificity of the mouse mdr1 and mdr3 drug efflux pumps.
Specific protein domains and amino acids responsible for the apparent capacity of P-glycoprotein (mdr) to recognize and transport a large group of structurally unrelated drugs have not been identified. We have introduced a single Ser----Phe substitution within the predicted TM11 domain of mdr1 (position 941) and mdr3 (position 939) and analyzed the effect of these substitutions on the drug-resistance profiles of these two proteins. Mutations at this residue drastically altered the overall degree of drug resistance conveyed by mdr1 and mdr3. The modulating effect of this mutation on mdr1 and mdr3 varied for the drugs tested: it was very strong for colchicine and adriamycin and moderate for vinblastine. For mdr1, the Ser941----Phe941 substitution produced a unique mutant protein that retained the capacity to confer vinblastine resistance but lost the ability to confer adriamycin and colchicine resistance. These results strongly suggest that the predicted TM11 domain of proteins encoded by mdr and mdr-like genes plays an important role in the recognition and transport of their specific substrates.


Translating guidelines to practice: findings from a multidisciplinary preventive cardiology programme in the west of Ireland.
The aim of this observational, descriptive study is to evaluate the impact of an intensive, evidence-based preventive cardiology programme on medical and lifestyle risk factors in patients at high risk of developing cardiovascular disease (CVD). Increased CVD risk patients and their family members/partners were invited to attend a 16-week programme consisting of a professional multidisciplinary lifestyle intervention, with appropriate risk factor and therapeutic management in a community setting. Smoking, dietary habits, physical activity levels, waist circumference and body mass index, and medical risk factors were measured at initial assessment, at end of programme, and at 1-year follow up. Adherence to the programme was high, with 375 (87.2%) participants and 181 (84.6%) partners having completed the programme, with 1-year data being obtained from 235 (93.6%) patients and 107 (90.7%) partners. There were statistically significant improvements in both lifestyle (body mass index, waist circumference, physical activity, Mediterranean diet score, fish, fruit, and vegetable consumption, smoking cessation rates), psychosocial (anxiety and depression scales and quality of life indices), and medical risk factors (blood pressure, lipid and glycaemic targets) between baseline and end of programme, with these improvements being sustained at 1-year follow up. These findings demonstrate how a holistic model of CVD prevention can improve cardiovascular risk factors by achieving healthier lifestyles and optimal medical management.


Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1.
Self-renewal of hematopoietic stem cells is vital for the sustained daily production of blood cells. Two recent studies have shown that the Polycomb-group gene Bmi-1 is indispensable for regulation of self-renewal by normal and leukemic stem cells. This identifies Polycomb-group genes as potential targets for therapeutic intervention in leukemia, and possibly other forms of cancer.


Impact on child vaccination completion rates of short message services (SMS) reminders in developing countries.
The Expanded Programme on Immunization has, since its inception, struggled to achieve high completion rates for child immunizations. The introduction of 2YL (second year of life) immunizations presents the programme with fresh challenges to assuring high completion rates. Using the same procedures as those employed in the 2017 article on SMS reminders, of which this is an update, I searched the NLM database for all recent articles from developing countries on SMS reminders for reduction of vaccination dropout rates. I summarized these and earlier articles in tabular form. The freshly reviewed articles are confirmatory of earlier studies which show an improvement in vaccination completion rates when SMS reminders are sent to mothers and other caregivers. All of the studies reviewed were based on pilot projects. It is time, and past time, to go to scale with SMS reminders, perhaps stand alone, or as part of a larger system of electronic immunization registers. There may be potential for use of WhatsApp in dropout reduction, thus far documented only in other public health applications.


Regulation of glutamine synthetase. V. Partial purification and properties of glutamine synthetase from Bacillus licheniformis.
The glutamine synthetase of Bacillus licheniformis has been obtained at about 15% purity. Sucrose gradient centrifugation gave a molecular weight value of approximately 612,000. Both l- and d-glutamate can be utilized as substrates in the biosynthetic reaction, although the l isomer was five times more active. The requirement for adenosine triphosphate (ATP) can be partially replaced by guanosine or inosine triphosphates, but not by cytidine or uridine triphosphates. The Mn(++) was required for activity, and the requirement cannot be satisfied with Mg(++). Maximal activity of the biosynthetic reaction was observed when ATP and Mn(++) were present in equimolar amounts. An excess of either reactant gave less activity. However, other purine and pyrimidine nucleotides, when added in combination with ATP, can partially substitute for ATP in attaining the equimolar ratio of nucleotide to Mn(++). A complex of ATP and Mn(++) is the preferred form of substrate. The B. licheniformis enzyme catalyzes the glutamyl transfer reaction but at a much slower rate than the Escherichia coli glutamine synthetase. Either adenosine diphosphate (ADP) or ATP can activate the glutamotransferase, although ADP is more active.


Effects of concentrated and dephytinized wheat bran and rice bran addition on bread properties.
Wheat bran and rice bran were concentrated in terms of dietary fiber and were dephytinized by two different methods (fermentation and hydrothermal). Untreated, concentrated, concentrated-dephytinized by fermentation method, and concentrated-dephytinized by hydrothermal method bran samples were each incorporated into flour at levels of 0, 10, 15, and 20%, and their effects on bread properties were investigated. Unprocessed wheat bran and rice bran addition decreased the volume yield, and the specific volume of the bread depends on the incorporation level. A further decrease was observed with the addition of concentrated bran. However, the dephytinization treatments slightly improved these values. The same pattern was observed for the total number of cells and the total cell area of bread crumbs. Both wheat bran and rice bran were observed to cause a darker crumb color, and the effects of bran samples on crumb color were more pronounced after the dephytinization treatment. The addition of concentrated wheat bran and rice bran significantly increased hardness, as well as decreasing springiness, cohesiveness, and resilience of the bread, depending on the bran levels. Although dephytinization treatments enhanced the textural properties of bread, these results were still inferior to those obtained using bread produced with untreated bran. Regarding the dephytinization treatments, the influence of fermentation treatment on bread properties was slightly beneficial compared to hydrothermal treatment. Consumption of dietary fiber offers a range of health benefits. Cereal bran has great potential as a dietary fiber source. However, this bran's high phytic acid content and adverse effects on bread quality limit that potential. It is possible to obtain high dietary fiber and low phytic acid bran samples through bran concentration and dephytinization treatments. The dephytinization treatment is an effective method for degradation of phytic acid. The negative effects of wheat bran and rice bran on bread quality decreased significantly following the dephytinization treatments. This study demonstrated that fiber-enriched bread with low phytic acid content and acceptable texture can be produced using concentrated and dephytinized bran.


Staphylococcus aureus outbreak in the intensive care unit of the largest public hospital in Quito, Ecuador.
Staphylococcus aureus is a frequent cause of nosocomial pneumonia and bacteremia worldwide. Classical and molecular epidemiology approaches were used to study a S. aureus outbreak in the intensive care unit (ICU) of one of the largest public hospitals in Quito. Staphylococcus aureus isolates from 17 patients and 19 potential carriers from the staff were collected from March 2007 to February 2008 and analyzed by pulsed-field gel electrophoresis (PFGE) to determine their clonal relationships. During this period the hospital reported 16 cases of hospital-acquired staphylococcal pneumonia and an apparent outbreak occurred from June to September 2007. DNA from these isolates formed six different PFGE patterns: four clonal groups, and two groups of clonally related isolates. Molecular typing failed to identify any staphylococcal reservoir among staff members. The current study suggested that a staphylococcal outbreak that occurred in the summer of 2007 was caused by different bacterial clones, although some clones were shared by two patients. Historical analysis of the staphylococcal infections in the ICU showed a higher incidence during the summer months, which coincided with the programmed personnel shift. This observation suggests that outbreaks might be produced by the introduction of improperly trained personnel.


Increasing levels of calcium salts of palm fatty acids affect production responses during the immediate postpartum and carryover periods in dairy cows.
Our objective was to determine the dose-response effects of calcium salts of palm fatty acids (CSPF) on nutrient digestibility and production responses of early-lactation dairy cows grazing on tropical pastures and to evaluate carryover effects throughout mid and late lactation. Forty multiparous dairy cows (Jersey × Holstein) with (mean ± standard error of the mean) 20 ± 1.69 kg of milk/d and 20 ± 5.0 d in milk were used in a randomized complete block design. During the treatment period, all cows were kept in a grazing system. The treatments were offered for 90 d (treatment period) and consisted of 4 increasing levels of CSPF: 0 (0 kg/d), 0.2 (0.2 kg/d), 0.4 (0.4 kg/d), and 0.6 (0.6 kg/d). Each treatment had 10 animals. Increasing CSPF from 0 to 0.6 kg/d replaced an equivalent amount of a corn-based concentrate supplement offered at 10 kg/d on an as-fed basis (8.96 kg/d as a dry matter basis). All cows were housed and received a diet without fat inclusion fed as total mixed ration once a day from 91 to 258 d of the experiment (carryover period). During the treatment period, increasing CSPF linearly decreased dry matter intake (1.20 kg/d), linearly increased neutral detergent fiber digestibility (3.90 percentage units), and quadratically increased total fat digestibility (6.30 percentage units at 0.4 kg/d CSPF). Increasing CSPF linearly increased the yields of milk (4.10 kg/d), milk fat (0.11 kg/d), milk lactose (0.19 kg/d), energy-corrected milk (ECM; 3.30 kg/d), and feed efficiency (ECM/dry matter intake, 0.34 kg/kg), and linearly decreased milk protein content (0.38 g/100 g), body weight change (0.05 kg/d), and body condition score (0.37). We observed interactions between CSPF and time during the carryover period. Overall, CSPF supplementation linearly increased or tended to increase milk yield until 202 d of the experiment with a similar pattern observed for all the other yield variables. In conclusion, supplementing CSPF from 0 to 0.6 kg/d during 90 d increased neutral detergent fiber and total fat digestibility and the yields of milk, milk fat, and ECM in early-lactation dairy cows grazing on tropical pastures. Most production measurements linearly increased during the treatment period, indicating that 0.6 kg/d CSPF was the best dose. Also, supplementing CSPF from 0 to 0.6 kg/d for 90 d during early lactation had positive carryover effects across mid and late lactation.


Toward On-line Parameter Estimation of Concentric Tube Robots Using a Mechanics-based Kinematic Model.
Although existing mechanics-based models of concentric tube robots have been experimentally demonstrated to approximate the actual kinematics, determining accurate estimates of model parameters remains difficult due to the complex relationship between the parameters and available measurements. Further, because the mechanics-based models neglect some phenomena like friction, nonlinear elasticity, and cross section deformation, it is also not clear if model error is due to model simplification or to parameter estimation errors. The parameters of the superelastic materials used in these robots can be slowly time-varying, necessitating periodic re-estimation. This paper proposes a method for estimating the mechanics-based model parameters using an extended Kalman filter as a step toward on-line parameter estimation. Our methodology is validated through both simulation and experiments.


Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma.
Eukaryotic translation initiation factor 3 subunit I (eIF3I) with transforming capability is often overexpressed in human hepatocellular carcinoma (HCC) but its oncogenic mechanisms remain unknown. We demonstrate that eIF3I is overexpressed in various cancers along with activated Akt1 phosphorylation and kinase activity in an eIF3I dose-dependent manner. A novel eIF3I and Akt1 protein interaction was identified in HCC cell lines and tissues and was required for eIF3I-mediated activation of Akt1 signaling. Expression of either antisense eIF3I or dominant negative Akt1 mutant suppressed eIF3I-mediated Akt1 oncogenic signaling and various other tumorigenic effects. Oncogenic domain mapping of the eIF3I and Akt1 interaction suggested that the C-terminal eIF3I interacted with the Akt1 kinase domain and conferred the majority of oncogenic functions. In addition, eIF3I interaction with Akt1 prevented PP2A dephosphorylation of Akt1 and resulted in constitutively active Akt1 oncogenic signaling. Importantly, concordant expression of endogenous eIF3I and phospho-Akt1 was detected in HCC cell lines and tissues. Treatment of eIF3I overexpressing HCC cells with the Akt1 specific inhibitor API-2 suppressed eIF3I-mediated tumorigenesis in vitro and in vivo. We describe a constitutive Akt1 oncogenic mechanism resulting from interaction of overexpressed eIF3I with Akt1 that prevents PP2A-mediated dephosphorylation. Overexpression of eIF3I in HCC is oncogenic and is a surrogate marker and therapeutic target for treatment with Akt1 inhibitors.


CYP2J2 - regulation, function and polymorphism.
Polyunsaturated fatty acids (PUFAs) undergo cytochrome P450 (CYP)-dependent oxidation to epoxides that modulate important physiological functions, including vasoactivity, inflammation, nociception, proliferation and viability. One of the most important human CYP epoxygenases is human CYP2J2 that is widely expressed in tissues, especially heart, vascular smooth muscle, salivary glands and placenta. Recent studies have shown that overexpression of CYP2J2 in vivo reverses several pathological processes in animals, including hypertension and other cardiovascular pathologies and insulin resistance. Information on the molecular regulation of CYP2J2 is sparse but supports roles for specificity protein-1 (Sp1) and activator protein-1 (AP-1) in transcription and the micro-RNA Let-7b in post-transcriptional regulation. Exposure to stress stimuli, including pro- and antioxidant factors and pro-inflammatory cytokines regulates CYP2J2, possibly in a cell-specific fashion. CYP2J2 is also subject to genetic variation and the promoter region SNP (CYP2J2-76G > T; *7 allele) reportedly decreases epoxygenase activity in vivo. Several studies have suggested that carriers of the *7 allele may be predisposed to adverse cardiovascular and related health outcomes, although other studies report different findings. Greater understanding of the mechanisms by which CYP2J2 is regulated could provide insights into important pathogenic processes in complex disease states. Such studies may also lead to the development of novel therapeutic strategies that seek to activate CYP2J2 expression in tissues. Additionally, the development of agents that promote fatty acid epoxide production, or stable analogs that retain the activities of the epoxides, offer promising new avenues for utilizing the beneficial actions of these molecules.


Spatially distinct domains of cell behavior in the zebrafish organizer region.
To determine the sequence of cell behaviors that is involved in the morphogenesis of the zebrafish organizer region, we have examined the dorsal marginal zone of vitally stained zebrafish embryos using time-lapse confocal microscopy. During the late-blastula stage, the zebrafish dorsal marginal zone segregates into several cellular domains, including a group of noninvoluting, highly endocytic marginal (NEM) cells. The NEM cell cluster, which lies in a superficial location of the dorsal marginal zone, is composed of both enveloping layer cells and one or two layers of underlying deep cells. The longitudinal position of this cellular domain accurately predicts the site of embryonic shield formation and occupies a homologous location to the organizer epithelium in Xenopus laevis. At the onset of gastrulation, deep cells underneath the superficial NEM cell domain undergo involution to form the nascent hypoblast of the embryonic shield. Deep cells within the NEM cell cluster, however, do not involute during early shield formation, but instead move in front of the blastoderm margin to form a loose mass of cells called forerunner cells. Forerunner cells coalesce into a wedge-shaped mass during late gastrulation and eventually become overlapped by the converging lateral lips of the germ ring. During early zebrafish tail elongation, most forerunner cells are incorporated into the epithelial lining of Kupffer's vesicle, a transient teleostean organ rudiment long thought to be an evolutionary vestige of the neurenteric canal. Owing to the location of NEM cells at the dorsal margin of blastula-stage embryos, as well as their early segregation from other deep cells, we hypothesized that NEM cells are specified by an early-acting dorsalizing signal. To test this possibility, we briefly treated early-blastula stage embryos with LiCl, an agent known to produce hyperdorsalized zebrafish embryos with varying degrees of expanded organizer tissue. In Li(+)-treated embryos, NEM cells appear either within expanded spatial domains or in ectopic locations, primarily within the marginal zone of the blastoderm. These results suggest that NEM cells represent a specific cell type that is specified by an early dorsal patterning pathway.


Rhinoplasty Photography: Lighting from Above Improves Visualization of Deviations and Irregularities.
Importance: Standard lighting with two flashlight diffusors for pre- and postoperative photography deviates from typical natural lighting and may mask relevant irregularities and deviations of the nose due a decreased contrast. Objective: This study aimed at testing the hypothesis that lighting from above improves the depiction of irregularities and deviations of the nose. Design, Setting, and Participants: This was a prospective randomized controlled trial at an academic tertiary medical center. Forty consecutive rhinoplasty candidates who requested a correction of irregularities or deviations of the nose were photographed first with standard anterolateral lighting (two studio strobe lights and diffusor boxes) and second with lighting from above. Ten lay judges rated the degree of irregularity or deviation of the nose on cropped images of the anterior view of the nose with both lighting conditions on a 5-point Likert scale. Results: Ratings for deviation or irregularity of the nose were higher for the photograph taken with lighting from above in 30 (75%), equal in 3 (7.5%), and lower in 7 (17.5%) of 40 pairs of photographs. The mean rating of nasal deformity for lighting from above (2.47; confidence interval [CI]95: 2.22-2.72) was significantly higher than mean rating for anterolateral lighting (1.86; CI95: 1.61-2.11). Conclusions and Relevance: Photographic documentation for rhinoplasty may be improved by including lighting from above if the standard lighting fails to adequately depict nasal irregularities or deviations.


Activity patterns and osmosensitivity of rat supraoptic neurones in perfused hypothalamic explants.
Extracellular recordings were obtained in vitro from supraoptic neurones in an explant of rat hypothalamus maintained viable through intravascular perfusion with artificial media. The spontaneous activity observed from 64% of cells included continuously active neurones (mean frequency 3.2 +/- 0.8 Hz) located throughout the nucleus, and phasically active neurones (8.6 +/- 0.6 Hz) located predominantly in the caudal half of the nucleus. Supraoptic neurones displayed antidromic activation (latency range 6.5-18.2 ms) following stimulation of the pituitary stalk and orthodromic excitatory or inhibitory responses following stimulation in the anteroventral third ventricular (AV3V) region. Synaptic responses were reversibly abolished during perfusion with media containing 12 mM-Mg2+. A 15-40 mosmol/l increase in the osmotic pressure of the perfusion media, through addition of NaCl, sucrose or mannitol, prompted nineteen of twenty-three cells to increase their discharge frequency. The patterns of response included the induction or simple increase in continuous firing frequency, the induction or enhancement of phasic or bursting activity and a change from continuous to phasic activity. Similar responses to an osmotic stimulus were obtained from thirteen of twenty-one supraoptic neurones, including two phasic neurones, where synaptic activity had been abolished during perfusion with 12 mM-Mg2+. Osmosensitivity appeared to be selective for supraoptic cells; no significant change in firing frequency was observed from any of six cells recorded in the lateral hypothalamus or thirteen cells recorded in the medial hypothalamus during exposure to a change in osmotic pressure of +20 to +40 mosmol/l, using either control media (seven cells) or media containing 12 mM-Mg2+ (twelve cells). These observations indicate that supraoptic neurones maintained in vitro can display spontaneous, antidromie , orthodromic and osmotically induced activity patterns identical to those observed with in vivo recordings. The persistence of a reduced osmosensitivity among supraoptic neurones in the absence of synaptic transmission indicates that although these cells can function as osmoreceptors, their osmosensitivity may be enhanced through synaptic input from adjacent neurones, possibly located in the AV3V area. The presence of phasic activity among supraoptic neurones maintained in media where synaptic transmission has been abolished suggests that the mechanisms responsible for such activity patterns are endogenous membrane properties of a subpopulation of supraoptic neurones.


Cognition and the perception of physical symptoms in the community-dwelling elderly.
Elderly people frequently complain of somatic (physical) symptoms that prompt them to seek medical intervention. The aim of this study was to evaluate the effect of cognitive impairment on somatic symptom complaints by the elderly. Symptoms (spontaneously reported and reported after explicit inquiry) pertaining to 15 organ systems were assessed in a random sample of 462 community-dwelling individuals over the age of 75 years. The symptoms increased with decreasing cognitive performance with no, very mild, and mild cognitive impairments as indicated on the Mini-Mental State Examination. The trend of increasing reports of symptom with decreasing cognitive performance was significant (p = .0001); the association remained significant after controlling for potential confounders in multivariate analysis (p < .05). The authors, who found that mild cognitive impairment was associated with perception of poorer body functioning, suggest that the clinical interpretation of somatic symptoms in the elderly should take cognitive impairment into account.