Metallic glass coating for improved needle tattooing performance in reducing trauma: analysis on porcine and pig skins.
The dissemination of tattooing into mainstream culture has raised concerns pertaining to the medical implications of these practices. This paper reports on the coating of tattoo needles with metallic-glass (MG) to reduce trauma to the skin. Extensive experimentation using pork samples and live pigs demonstrated the beneficial effects of non-stick MG coatings. Following 30 insertions into pork skin, significantly less tissue adhered to the MG-coated needles than to uncoated needles. MG-coated needles were also shown to reduce the spread of pigment to the surface of surrounding skin by up to 57%. This resulted in narrower tattoo lines of higher density, indicating that MG-coated needles could be useful in high-resolution tattooing. Histopathological analysis on live pigs revealed severe trauma induced by bare needles, as indicated by the secretion of fluids immediately after tattooing. The wounds formed by coated needles closed within 2 h after tattooing; however, those formed by bare needles remained open for at least 2 h and inflammation was still observed after 3 days. At 5 days after tattooing, skin punctured by the coated needle was entirely healed, whereas skin punctured by the bare needle was still covered with scabs. In addition to the medical benefits, it appears that MG-coated needles could improve the quality of tattoos, based on the fact that the amount of pigment retained in the skin is inversely proportional to the trauma caused by needles.


Subthalamic deep brain stimulation for primary dystonia: defining an optimal location using the medial subthalamic nucleus border as anatomical reference.
Although the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia. Data from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke-Fahn-Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI. The clinical improvement showed a significant negative correlation with the y-axis position (anterior-posterior; A+, P-). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border. STN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani's line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.


Thrombus resolution and hemodynamic recovery using ultrasound-accelerated thrombolysis in acute pulmonary embolism.
To evaluate retrospectively the safety profile and clinical success of ultrasound-accelerated thrombolysis for acute pulmonary embolism (PE) with a standard lytic infusion protocol. A retrospective study was performed at a single center treating patients with acute PE between October 2009 and April 2012. On diagnosis of submassive or massive PE by pulmonary computed tomography angiography or ventilation/perfusion scan, all patients received anticoagulation and treatment using the EkoSonic endovascular system (EKOS Corporation, Bothell, Washington). The ultrasound-accelerated thrombolytic infusion catheters were placed into the affected pulmonary arteries to facilitate administration of recombinant tissue plasminogen activator at 0.5-1.0mg/h/catheter. Treatment of 60 patients (35 men, 25 women; age 61 y±16; 53 bilateral PE; 48 submassive PE) resulted in complete thrombus clearance (≥90%) in 57% and near-complete (50%-90%) clearance in 41% of patients after infusion of 35.1 mg±11.1 of recombinant tissue plasminogen activator over 19.6 hours±6.0. Measurements before and after treatment showed a decrease in pulmonary artery pressure (47 mm Hg±15 to 38 mm Hg±12 [systolic], P<.001) and Miller score (25±3 to 17±6, P<.001). There were 57 patients who survived to discharge. All three patients who died in the hospital presented with massive PE. On 90-day follow-up, 56 patients (93%) were alive. The current study demonstrates effectiveness and safety of ultrasound-accelerated thrombolysis in patients with acute PE with a large thrombus burden.


Identifying improved TSPO PET imaging probes through biomathematics: the impact of multiple TSPO binding sites in vivo.
To date, ¹¹C-(R)-PK11195 has been the most widely used TSPO PET imaging probe, although it suffers from high non-specific binding and low signal to noise. A significant number of 2nd generation TSPO radioligands have been developed with higher affinity and/or lower non-specific binding, however there is substantial inter-subject variation in their affinity for the TSPO. TSPO from human tissue samples binds 2nd generation TSPO radioligands with either high affinity (high affinity binders, HABs), or low affinity (LABs) or expresses both HAB and LAB binding sites (mixed affinity binders, MABs). The expression of these different TSPO binding sites in human is encoded by the rs6971 polymorphism in the TSPO gene. Here, we use a predictive biomathematical model to estimate the in vivo performances of three of these 2nd generation radioligands (¹⁸F-PBR111, ¹¹C-PBR28, ¹¹C-DPA713) and ¹¹C-(R)-PK11195 in humans. The biomathematical model only relies on in silico, in vitro and genetic data (polymorphism frequencies in different ethnic groups) to predict the radioactivity time course in vivo. In particular, we provide estimates of the performances of these ligands in within-subject (e.g. longitudinal studies) and between-subject (e.g. disease characterisation) PET studies, with and without knowledge of the TSPO binding class. This enables an assessment of the different radioligands prior to radiolabelling or acquisition of any in vivo data. The within-subject performance was characterised in terms of the reproducibility of the in vivo binding potential (%COV[BP(ND)]) for each separate TSPO binding class in normal and diseased states (50% to 400% increase in TSPO density), whilst the between-subject performance was characterised in terms of the number of subjects required to distinguish between different populations. The results indicated that the within-subject variability for ¹⁸F-PBR111, ¹¹C-PBR28 and ¹¹C-DPA713 (0.9% to 2.2%) was significantly lower than ¹¹C-(R)-PK11195 (16% to 36%) for HABs and MABs in both normal and diseased states. For between-subject studies, sample sizes required to detect 50% differences in TSPO density with the 2nd generation tracers are approximately half that required with ¹¹C-(R)-PK11195 when binding class information is known a priori. As binding class can be identified using a simple genetic test or from peripheral blood assays, the combination of binding class information with 2nd generation TSPO imaging data should provide superior tools to investigate inflammatory processes in humans in vivo.


Transcutaneous oxygen tension during exercise in patients with pulmonary emphysema.
Transcutaneous PO2 (tcPO2) and arterial PO2 (PaO2) were compared during exercise in six patients with pulmonary emphysema. For calibration purposes, the tcPO2 electrode was first attached to the skin and after stabilisation its reading was adjusted to correspond to the PO2 of an initial arterial blood sample. It was shown that tcPO2 measurement could follow accurately the rapid changes in PaO2 occurring during exercise. Sixty-eight paired comparisons of PaO2 and tcPO2 were available and the regression equation was given by: tcPO2 (mmHg) = 0.98 PaO2 + 0.7 (correlation coefficient, 0.985; 95% confidence limits, 5.7 mmHg).


Genetic analysis of the Amerindian Kichwas and Afroamerican descendents populations from Ecuador characterised by 15 STR-PCR polymorphisms.
Allele frequency data for the 15 STR systems and Amelogenine were determined in a population sample of healthy Amerinidian Kichwas and Blacks individuals. All loci met Hardy-Weinberg expectations and the high discrimination power of combined system showed the forensic efficiency of these genetic markers.


The metabolism of exogenous histamine by aortic tissues.
A thin layer chromatographic system is presented for the separation of histamine (H), 1,4-methylhistamine (M), acid metabolites comprising imidazole and methylimidazole acetic acids (A) and N-acetylhistamine (N). The system was applied to separation of the histamine metabolites formed following incubation of rabbit and guinea-pig thoracic aorta segments with labelled histamine. The effects of various agents known to affect histamine uptake, storage and metabolism in vascular tissue were studied on the disposition of histamine metabolites.


[The role and biological significance of toll-like receptors in the anti-infectious resistance of the organism].
Modem conceptions of the role of toll-like receptors (TLR) in the innante immunity mechanisms realization and data on the interaction between TLR and pattern-associated molecular proteins of microbial or endogenic origin are presented in the review.


Exploring the genetic determinants underlying the differential production of an inducible chromosomal cephalosporinase - BlaB in Yersinia enterocolitica biotypes 1A, 1B, 2 and 4.
Yersinia enterocolitica is an enteric bacterium which can cause severe gastroenteritis. Beta-lactams are the most widely used antibiotics against Y. enterocolitica. Y. enterocolitica produces two chromosomal β-lactamases, BlaA and BlaB. BlaB is an Ambler Class C inducible broad spectrum cephlaosporinase which showed differential enzyme activity in different biotypes of Y. enterocolitica. The expression of blaB is mainly regulated by ampR- the transcriptional regulator and, ampD - which helps in peptidoglycan recycling. The aim of this study was to identify and characterize genetic determinants underlying differential enzyme activity of BlaB in Y. enterocolitica biotypes 1 A, IB, 2 and 4. Thus, ampR, blaB and ampD were PCR-amplified and modeled in silico. The intercistronic region containing promoters of ampR and blaB was also investigated. Our results indicated that blaB was more inducible in biotypes 2 and 4, than in biotypes 1 A and 1B. Superimposition of in silico modeled proteins suggested that variations in amino acid sequences of AmpR, BlaB and AmpD were not responsible for hyper-production of BlaB in biotypes 2 and 4. Analysis of promoter regions of ampR and blaB revealed variations at -30, -37 and -58 positions from blaB transcription start site. Studies on relative expression levels of blaB in different biotypes by qRT-PCR indicated that nucleotide variations at these positions might contribute to a higher enzyme activity of BlaB in biotypes 2 and 4. However, this is a preliminary study and further studies including more strains of each biotype are required to strengthen our findings. Nevertheless, to the best of our knowledge, this is the first study which has investigated the genetic determinants underlying differential inducible production of BlaB in different biotypes of Y. enterocolitica.


Comparison through immunoblotting of glutamic acid decarboxylase (GAD) from newborn and adult rat brain.
Immunochemical characterization of glutamic acid decarboxylase (GAD) from brain extracts of newborn and adult rats was investigated using a GAD antiserum that was previously raised against brain GAD from adult rats. According to the immunoprecipitation and saturation curves, no significant differences could be found as to the recognition of newborn and adult GAD by the antiserum. On immunoblots, both extracts revealed the same two immunolabelled bands (mol.wt. 59,000 and 62,000 +/- 2000 Da). In both cases, the lightest band showed the strongest staining. Quantitative analysis of the immunolabelling indicated that each immunolabelled band was enriched about 10-fold in the adult brain extract. These data did not reveal any difference between newborn and adult GAD that was reminiscent of the difference found in an earlier study between GAD from lower and higher vertebrates. Whatever the regulatory mechanism responsible for the presence of two forms of GAD in the adult brain, it is already fully operative in newborn animals.


Microplastic pollution in lakeshore sediments: the first report on abundance and composition of Phewa Lake, Nepal.
Microplastic pollution in a freshwater environment has captured the attention of the scientific world in recent years. Microplastic is a new area of research in the freshwater of Nepal. Hence, the present study aims to examine the concentration, distribution, and characteristics of microplastic pollution in the sediments of Phewa Lake. Twenty sediment samples were collected from 10 sites to cover the vast area (5.762 km2) of the lake. The mean abundance of microplastic was 100.5 ± 58.6 items/kg dry weight. The average abundance of microplastics in five sections of the lake showed a significant difference (test statistics = 10.379, p < 0.05). Fibers (78.11%) dominated the sediments of Phewa Lake in all sampling sites. Transparent was the prominent color observed followed by red and altogether 70.65% of the microplastics detected were found at 0.2-1 mm size class. Fourier transform infrared spectroscopy (FTIR) analysis of visible microplastic particles (1-5 mm) confirmed polypropylene (PP) (42.86%) as the dominant polymer type followed by polyethylene (PE). This study can help to bridge the knowledge gap regarding the microplastic pollution in freshwater shoreline sediments of Nepal. Furthermore, these findings would create a new research area to explore the impact of plastic pollution which has been ignored in Phewa Lake.


Evidence that dopaminergic sympathetic axons supply the medullary arterioles of human kidney.
The ability of the kidney to excrete sodium appears to depend on release of dopamine from intrarenal sources. In the present study, we have used immunohistochemistry to examine the possibility that renal dopaminergic nerves constitute one of these sources. We found that the sympathetic axons supplying cortical structures in human kidney contain tyrosine hydroxylase-like immunoreactivity but lack DOPA decarboxylase-like immunoreactivity. By contrast, the vasa recta arterioles of the renal medulla are supplied by varicose tyrosine hydroxylase-positive nerve fibres, some of which also contain DOPA decarboxylase. As DOPA decarboxylase has been demonstrated in other situations to be a selective marker for dopaminergic terminal axons, our results suggest the innervation of renal medullary blood vessels in man by both noradrenergic and dopaminergic sympathetic nerves.


In vivo single-cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection.
The strategies deployed by antibiotic-resistant bacteria to counteract host defences are poorly understood. Here, we elucidate a novel host-pathogen interaction resulting in skewing lung macrophage polarisation by the human pathogen Klebsiella pneumoniae. We identify interstitial macrophages (IMs) as the main population of lung macrophages associated with Klebsiella. Single-cell transcriptomics and trajectory analysis of cells reveal type I IFN and IL10 signalling, and macrophage polarisation are characteristic of infected IMs, whereas Toll-like receptor (TLR) and Nod-like receptor signalling are features of infected alveolar macrophages. Klebsiella-induced macrophage polarisation is a singular M2-type we termed M(Kp). To rewire macrophages, Klebsiella hijacks a TLR-type I IFN-IL10-STAT6 axis. Absence of STAT6 limits Klebsiella intracellular survival and facilitates the clearance of the pathogen in vivo. Glycolysis characterises M(Kp) metabolism, and inhibition of glycolysis results in clearance of intracellular Klebsiella. Capsule polysaccharide governs M(Kp). Klebsiella also skews human macrophage polarisation towards M(Kp) in a type I IFN-IL10-STAT6-dependent manner. Klebsiella induction of M(Kp) represents a novel strategy to overcome host restriction, and identifies STAT6 as target to boost defences against Klebsiella.


Global cardiovascular disease risk management in italian patients with metabolic syndrome in the clinical practice setting.
Metabolic syndrome is a highly prevalent condition in the Italian population. This study assesses the feasibility and efficacy of a multifactorial approach for primary prevention of cardiovascular disease risk assessment in patients with metabolic syndrome in the daily clinical practice setting. 726 patients were enrolled (males : females = 7 : 3), their ages ranging from 26 to 70 years, with metabolic syndrome and cardiovascular death risk ≥5%, computed by means of the European Systematic COronary Risk Evaluation (SCORE) algorithm. The first phase (3 months) consisted of an improvement in lifestyle and, if necessary, the initial administration of an antihypertensive therapy (valsartan 160 mg/day for patients with blood pressure ≥140/90 mmHg and ≥130/80 mmHg for diabetic patients). During phase 2 (6 months), patients with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (≥130/80 mmHg for diabetic patients) were administered valsartan 160 mg/day + hydrochlorothiazide 12.5 mg/day combined; those with total cholesterol levels ≥190 mg/dL (≥175 mg/dL for diabetic patients) started treatment with fluvastatin 80 mg prolonged release (XL), as prescribed in the guidelines. A control group was approached with another conventional treatment. After 9 months of monitoring, the SBP dropped by 27 mmHg in the valsartan-treated patients and by 11 mmHg in the control group, while the DBP dropped by 12 mmHg in the former group and 2 mmHg in the latter. Total cholesterolaemia was reduced by 47 mg/dL in patients undergoing fluvastatin and valsartan therapy, by 19 mg/dL in those treated with valsartan only and by 33 mg/dL in those administered another conventional treatment. Relative risk reduction observed after 9 months, compared with the beginning of the study, was almost 48% in the valsartan/valsartan + fluvastatin group, versus 28% observed with the other conventional treatment. The reduction of risk at 60 years of age was an average of 39% at 3 months and 48% at 9 months, compared with the beginning of the study. Therapeutic success was accomplished with 78% of the patients treated with valsartan/valsartan + fluvastatin, compared with 47% of patients in the conventional therapy group. The present study demonstrated that the normalization of the main cardiovascular risk factors in patients with metabolic syndrome may be easily achieved in standard clinical practice settings, by leading an adequate lifestyle and, if necessary, the administration of antihypertensive and/or lipid-lowering monotherapy at the usual doses.


Prospective clinical validation of 3D printed nasopharyngeal swabs for diagnosis of COVID-19.
COVID-19 greatly disrupted the global supply chain of nasopharyngeal swabs, and thus new products have come to market with little data to support their use. In this prospective study, 2 new 3D printed nasopharyngeal swab designs were evaluated against the standard, flocked nasopharyngeal swab for the diagnosis of COVID-19. Seventy adult patients (37 COVID-positive and 33 COVID-negative) underwent consecutive diagnostic reverse transcription polymerase chain reaction testing, with a flocked swab followed by one or two 3D printed swabs. The "Lattice Swab" (manufacturer Resolution Medical) demonstrated 93.3% sensitivity (95% CI, 77.9%-99.2%) and 96.8% specificity (83.3%-99.9%), yielding κ = 0.90 (0.85-0.96). The "Origin KXG" (manufacturer Origin Laboratories) demonstrated 83.9% sensitivity (66.3%-94.6%) and 100% specificity (88.8%-100.0%), yielding κ = 0.84 (0.77-0.91). Both 3D printed nasopharyngeal swab results have high concordance with the control swab results. The decision to use 3D printed nasopharyngeal swabs during the COVID-19 pandemic should be strongly considered by clinical and research laboratories.


Peripheral serotoninergic receptor sensitivity in senile dementia of the Alzheimer type.
Platelet aggregation induced by 5-hydroxytryptamine (5-HT) was used as a measure of the functional responsiveness of peripheral 5-HT receptors in controls and drug-free patients suffering from senile dementia of Alzheimer type (SDAT). No significantly different aggregatory response (5-HT/ADP ratio) was noted between the two groups of subjects. If the receptor mediating this response is a 5-HT2 receptor, there is no evidence to suggest that the functional activity of this system is abnormal in SDAT.


A Simple Quantitative Assay for Measuring β-Galactosidase Activity Using X-Gal in Yeast-Based Interaction Analyses.
Yeast-based interaction assays to determine protein-protein and protein-nucleic acid interactions commonly rely on the reconstitution of chimeric transcription factors that activate the expression of target reporter genes. The enzyme β-galactosidase (β-gal), coded by the LacZ gene of Escherichia coli, is a widely used reporter in yeast systems, and its expression is commonly assessed by evaluating its activity. X-gal (5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside) is an inexpensive and sensitive substrate of β-gal, whose hydrolysis results in an intensely blue colored and easily detectable end product, 5,5'-dibromo-4,4'-dichloro-indigo. The insoluble nature of this end product, however, makes X-gal-based assays unsuitable for direct spectrophotometric absorbance quantification. As such, the use of X-gal is mostly restricted to solid-support approaches, such as colony lift or agar plate assays, which often only provide a qualitative readout. In this article, we describe a quantitative solid-phase X-gal assay to measure protein-protein interaction strength in yeast cells using a simple and low-cost experimental setup. We have optimized multiple aspects of the assay, namely sample preparation, reaction time, and quantification method, for speed and consistency. By integrating the use of a freely available ImageJ-based plugin, we have further standardized the assay for reliability and reproducibility. This improved quantitative X-gal assay can be performed in a standard molecular biology lab without the need for any specialized equipment other than an inexpensive and widely accessible smartphone camera. To exemplify the protocol, we provide detailed step-by-step instructions to perform a quantitative X-gal assay to assess the interaction between two Arabidopsis thaliana proteins, SUPPRESSOR OF PHYA-105 1 (SPA1) and PRODUCTION OF ANTHOCYANIN PIGMENT 2 (PAP2). To demonstrate the sensitivity of our assay in detecting weaker interactions, we also compare the results with a liquid-phase assay that uses ONPG (ortho-nitrophenyl-β-galactopyranoside) as a substrate for β-gal. The quantitative X-gal assay described here can easily be adapted for high-throughout interaction studies and protein domain mapping, even in yeast strains with low levels of LacZ expression. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of competent yeast cells and transformation Alternate Protocol 1: In-house preparation of yeast competent cells for use in lithium acetate (LiAc)-mediated yeast transformation Support Protocol: Long-term storage and revival of frozen yeast strain stocks Basic Protocol 2: Measuring β-galactosidase activity via the quantitative X-gal assay Alternate Protocol 2: Quantification of interaction strength using liquid ONPG assay.


Nurse Staffing Levels and Patient-Reported Missed Nursing Care.
A total of 729 inpatients were surveyed using the MISSCARE Survey-Patient. Missed timeliness, patient reports of the time it took for them to receive care from nursing staff, was negatively associated with total nursing staff hours of care per patient-day (r = -0.09, P = .015), registered nurse (RN) hours per patient-day (r = -0.14, P = .0002), and RN skill mix (r = -0.13, P = .0004). RN skill mix was also a predictor of missed timeliness (P = .01).


Accuracy of Doppler echocardiography in quantification of left to right shunts in adult patients with atrial septal defect.
In previous experimental and pediatric studies, the ratio of pulmonary to systemic flow (Qp/Qs) was accurately estimated by Doppler echocardiography in various cardiac shunt lesions. The purpose of this study was to assess the accuracy of pulsed Doppler echocardiography in determining the magnitude of shunt flow in adult patients with an ostium secundum type atrial septal defect. In 32 patients with high quality echocardiograms and excellent Doppler signals, blood flow was measured in the right and left ventricular outflow tract by Doppler echocardiography. In 16 patients without heart disease, the correlation (r) between systemic (Qs) and pulmonary (Qp) blood flow was 0.96 (SEE = 0.417 liter/min, y = 1.05x - 0.21) and the mean Qp/Qs ratio was 1.01 +/- 0.09. In 16 patients with an atrial septal defect, the Qp/Qs ration measured by oximetry ranged from 1.34 to 4.61 and by pulsed Doppler echocardiography from 1.31 to 4.46 (p = NS). In these 16 patients, the correlation between the Qp/Qs ratio determined by oximetry and pulsed Doppler echocardiography was significant (r = 0.82, SEE = 0.54). In the total group of 32 patients, the correlation was stronger (r = 0.93, SEE = 0.37). Systematic differences between the invasive and noninvasive shunt calculations did not occur. Thus, in adult patients with an atrial septal defect of the secundum type and high quality echocardiograms, the magnitude of left to right shunt can be accurately assessed by pulsed Doppler echocardiography. In the absence of pulmonary hypertension, pulsed Doppler echocardiography provides precise information for the decision to undertake conservative or operative treatment.


Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing-Remitting Multiple Sclerosis.
We aimed to investigate the extent of alterations in the pro/antioxidant balance in the blood of patients with relapsing-remitting multiple sclerosis (RRMS) in relation to drug-modified therapy, gender, disability score, and disease duration. 161 patients (67 men and 94 women, aged 24-69 years, median 43.0) and 29 healthy individuals (9 men and 20 women, aged 25-68 years, median 41.0) were included in the study. We measured the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) as well as the concentration of interleukin-6 (IL-6), lipid peroxidation parameters (LPO), total oxidant status (TOS), and total antioxidant capacity (TAS). The activity of SOD did not show any significant differences between patients with RRMS and the control group in our study. In contrast, significant decreased GPx activity and increased CAT activity was observed in the blood of patients with RRMS compared to the control group. Additionally, the activity of CAT was influenced by gender and the use of disease-modifying therapies. Disease-modifying therapies also affected the concentration of TOS, TAS, and LPO. Our studies indicated that enhancing GPx activity may be more beneficial to providing potential therapeutic strategies aimed at modulating antioxidant defenses to mitigate oxidative stress in this disease.


[First diagnosis of systemic sclerosis based on ocular complications].
Systemic sclerosis is a chronic connective tissue disease in which immune system dysfunction alters the structure and function of blood vessels. It is characterized by enhanced tissue fibrosis, which may rapidly affect a large area of the skin as well as internal organs. Dry eye symptoms are the most common ocular findings. This case presents a 51-year-old male patient suffering from blurred vision in the left eye. The ophthalmoscopic examination revealed retinal thrombotic microangiopathy in both eyes. Spectral-domain optical coherence tomography (SD OCT) showed a macular edema in the left eye. Although these ocular symptoms do not represent the initial manifestation of the primary disease, correct diagnosis was only made in the context of the retinal findings. Retinal microangiopathic lesions can play a seminal role in diagnosing systemic sclerosis.


Color as a variable in making an erotic film more arousing.
Eight adult male subjects participated in a counterbalanced, repeated-measures design to determine the relative efficacy of color and black-and-white visual sexual stimuli in eliciting sexual arousing, as objectively measured by a mercury-in-rubber strain gauge transducer. There were no consistent or significant differences in either the intensity of the pattern of penile responding during color and black-and-white presentations of the same film.


Episodic apnea: gastroesophageal reflux associated with gastric organo-axial malrotation: a case report.
Gastroesophageal reflux is a normal physiologic process occurring several times a day in healthy infants. On the other hand, symptoms such as failure to thrive, feeding or sleeping problems, chronic respiratory distress, persistent forceful vomiting, and choking may indicate reflux associated with underlying anatomic, neurological, or infectious abnormalities. Gastric malrotation is an extremely rare disorder in the pediatric population and one of the anatomic causes associated with severe reflux, which could lead to serious complications. In such cases, life-threatening symptoms overlapping with other diseases cause delayed diagnosis and treatment. We report a 2.5-month-old white girl diagnosed with gastric malrotation-related reflux, which caused inadequate weight gain, feeding difficulties, episodes of apnea with cyanosis, and choking after successive coughing, hence previously misdiagnosed as epilepsy and pertussis. Life-threatening symptoms in an infant with reflux suggest anatomic, neurological, or infectious conditions. Gastric malrotation is more common than generally thought and specifically looked for in young children with severe reflux symptoms, and should be diagnosed and treated as soon as possible.


Reductive desorption of 11-mercaptoundecanoic acid monolayers modified by covalent attachment of 1,3- and 1,4-phenylenediamine.
1,3- and 1,4-phenylenediamine were covalently attached to a self-assembled monolayer of 11-mercaptoundecanoic acid by formation of an amide bond. Bonding of the phenylenediamine isomers was confirmed by the presence of infrared features attributable to ring vibrational modes, the amide I vibration, and the amide II vibration in the reflection-absorption infrared spectrum of the modified interface. Reductive desorption peak potentials were shifted by 120 mV for the monolayer modified by 1,4-phenylenediamine and by 90 mV for the monolayer modified by 1,3-phenylenediamine relative to the desorption potential of the unmodified 11-mercaptoundecanoic acid monolayer. These potential shifts represent 23 and 17 kJ/mol stabilization of the monolayers modified by 1,4- and 1,3-phenylenediamine, respectively. Some of the additional stabilization energy is attributed to lateral hydrogen bonding between the amide groups and unreacted carboxylic acid groups in the monolayer. The difference between the stabilization energies for the interfaces modified with the different phenylenediamine isomers is attributed to structural differences between the isomeric monolayers influencing the molecular packing of the modified interface.


Detection of human papillomavirus genotypes with liquid bead microarray in cervical lesions of northern Chinese patients.
Human papillomavirus (HPV) is the main cause of cervical cancer. Blending multiplex polymerase chain reaction (PCR) amplification and multiplex hybridization to liquid bead microarray (LBMA), we detected and identified 25 common HPV genotypes using type-specific primers for HPV E6 and E7 genes in cervical lesions of northern Chinese patients. Of the 511 cervical samples, 349 (68.3%) were found to be HPV positive by HPV-LBMA. The distribution was 22 HPV positive of 100 in the control group (22%), 41 of 80 with chronic cervicitis (51%), 80 of 99 with cervical intraepithelial neoplasia (CIN) I (81%), 46 of 56 with CIN II (82%), 67 of 74 with CIN III (90%), and 93 of 102 with invasive cervical carcinoma (91%). HPV-16 was the most frequent genotype in the CIN and cervical cancer groups. The most common genotypes were HPV-16 (28%), HPV-58 (14%), HPV-52 (14%), HPV-18 (8%), and HPV-33 (7%) in the CIN group, and HPV-16 (63%), HPV-52 (9%), HPV-18 (7%), HPV-58 (7%), and HPV-33 (5%) in the cervical cancer group. HPV-LBMA found multiple genotypes in 1 of 22 control (4%), 64 of 193 CIN (33%), and 22 of 93 cervical cancer (24%). The HPV-LBMA results were compatible with those of PCR and DNA sequencing. HPV-LBMA is a simple, high-throughput method that provides useful information on viral genotype and multiple HPV infections in cervical lesions. In northern China, the most common high-risk HPV genotypes seem to be HPV types 16, 58, 52, 18, and 33. Genetic information on HPV in cervical specimens could provide particular benefits in the management of cervical lesions.


Three-dimensional magnetic resonance elastography combining proton-density fat fraction precisely identifies metabolic dysfunction-associated steatohepatitis with significant fibrosis.
Patients with metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis (fibrosis stage≥2), known as Fibro-MASH, are at increased risk of liver-related outcomes and lower rates of spontaneous disease regression. The aim was to investigate three-dimensional MR elastography (3D-MRE) combining proton-density fat fraction (PDFF) as a means of identifying Fibro-MASH. Forty-eight New Zealand rabbits were fed a high-fat/cholesterol or standard diet to obtain different disease activity and fibrosis stages. Shear stiffness (SS) and Damping Ratio (DR) were derived from 3D-MRE, whereas PDFF was from a volumetric 3D imaging sequence. Steatosis grade, metabolic dysfunction-associated steatotic liver disease activity score (MAS), and fibrosis stage were diagnosed histologically. Serum markers of fibrosis and inflammation were also measured. Correlation and comparison analysis, Receiver operating characteristic curves (ROC), Delong test, logistic regression analysis, and Net reclassification improvement (NRI) were performed. PDFF correlated with steatosis grade (rho = 0.853). SS increased with developed liver fibrosis (rho = 0.837). DR correlated with MAS grade (rho = 0.678). The areas under the ROC (AUROCs) of SS for fibrosis grading were 0.961 and 0.953 for ≥F2, and ≥ F3, respectively. All the biochemical parameters were considered but excluded from the logistic regression analysis to identify Fibro-MASH. FF, SS, and DR were finally included in the further analysis. The three-parameter model combining PDFF, SS, and DR showed significant improvement in NRI over the model combining SS and PDFF (AUROC 0.973 vs. 0.906, P = 0.081; NRI 0.28, P < 0.05). 3D-MRE combining PDFF may characterize the state of fat content, disease activity and fibrosis, thus precisely identify Fibro-MASH.


Homogeneous immunoassay utilizing fluorescence resonance energy transfer from quantum dots to tyramide dyes deposited on full immunocomplexes.
There is an urgent need for homogeneous immunoassays that offer sufficient sensitivity for routine clinical practice. In this study, we have developed a highly sensitive, fluorescence resonance energy transfer (FRET)-based homogeneous immunoassay. Unlike previous FRET-based homogeneous immunoassays, where acceptors were attached to antibody molecules located far from the donor, we employed acceptors to label the entire sandwich-structured immunocomplex, including two antibodies and one antigen. As a result, the FRET signal was amplified by a factor of 10, owing to the reduced distance between the donor and acceptors. We validated our method by quantifying carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) in PBS buffer and blank plasma. The limits of detection (LOD) for CEA and AFP in both PBS buffer and blank plasma were comparable, reaching sub-femtomolar levels. Furthermore, we successfully quantified CEA and AFP in three human plasma samples, thereby confirming the reliability of our method for clinical applications.


Leprosy in children in Cuba: Epidemiological and clinical description of 50 cases from 2012-2019.
In 1993, Cuba achieved leprosy elimination according to the World Health Organization's (WHO) indicator of less than one case per 10,000 population. Despite this achievement, detection of new cases occurs every year among all age groups including children. Detection of new cases in children reveals persistent transmission of the infection. To describe the clinical and epidemiological features of leprosy in individuals younger than 15 years (childhood leprosy) reported to the Cuban National Leprosy Control Program (NLCP) between 2012 and 2019. We conducted a retrospective descriptive study between 2012 and 2019 to assess the clinical and epidemiologic features of individuals under the age of 15 years with a confirmed diagnosis of leprosy reported to the NLCP. We reviewed the NLCP database and collected data to better define the total number of cases of leprosy in adults, children (younger than 15 years). We assessed socio-demographic variables (age, gender, and province of residence) as well as variables of clinical interest including operational classification and staging at diagnosis, bacillary index, grade of disability by WHO staging. Additionally, we evaluated epidemiological variables including passive versus active surveillance of cases, contact investigation focusing specifically in household transmission, and the degree of kinship as well as standing of the child within the focus of transmission when there were additional cases. We identified fifty children during the study period corresponding to 3% of the overall cases of leprosy comprising all age groups in Cuba. In the age group younger than 15 years, the majorities of cases was from the Granma province and most were between the ages of 10 and 14 years. Clinically, multibacillary/lepromatous forms were the most common type identified with positive bacillary index. The majority of children diagnosed with leprosy during our study period had a history of a relative with a confirmed diagnosis of leprosy. Detection of cases of leprosy in individuals younger than 15 years of age in Cuba demonstrates ongoing transmission of M. leprae in specific geographic hotspots. Its frequency in the early adolescence, the predominant clinical forms, and the mode of detection associated with sources of suspected familiar infection demonstrated that there is a need for further efforts by the NLCP to conduct active surveillance activities among affected communities to identify cases of leprosy earlier with the goal of preventing further household and community transmission.


Ergosterol synthesis and population analysis of a fed-batch fermentation in Saccharomyces cerevisiae.
Saccharomyces cerevisiae with an increased content of ergosterol or delta 5,7-sterols, growing on a molasses medium with a feed of ethanol and (NH4)2HPO4, was analyzed as to the age of cell population. The analysis was done by centrifugation in a dextran gradient and by a fluorescence-microscopic technique. In the phase of batch fermentation at a mean specific growth rate of 0.22 h-1 daughter cells contained less than 1% ergosterol while the ergosterol content of mother cells depended on the time of cultivation, a maximum level (4%) being found after two generation times. In the fed-batch phase at a mean growth rate of 0.052 h-1, both daughter and mother cells contained about the same amount of ergosterol (4.7-5.5%). Differences between daughter and mother cells are discussed in view of the relationship between the growth rate and the growth cycle.


Delayed-release bleomycin. Comparative pharmacology of bleomycin oil suspension and bleomycin in saline.
Experimental and clinical evidence indicates that bleomycin by continuous infusion is superior to intermittent administration. Continuous infusion is less convenient, however. It has been suggested that a suspension of bleomycin in sesame oil, given by IM injection, simulates a continuous infusion. The pharmacokinetics of this formulation have been compared with those of bleomycin in saline following IM injection, in six patients. The pharmacokinetic profiles of the two formulations were similar. The only difference between the profiles was the long terminal half-life at very low concentrations between 12 and 48 h after injection of the oil suspension. This difference is of unknown, but doubtful, clinical significance.


Hippopotamidae (Cetartiodactyla, Hippopotamoidea) from Kanapoi, Kenya, and the taxonomic status of the late early Pliocene hippopotamids from the Turkana Basin.
New hippopotamid specimens recently collected at Kanapoi (ca. 4 Ma) are similar to the taxon previously recognized in this site and referred to aff. Hippopotamus protamphibius. Their examination provided the opportunity to reassess the taxonomic status of this taxon. It appears different from the late Miocene hippopotamids from the Turkana Basin (prominently Archaeopotamus harvardi), but also differs from the late Pliocene-early Pleistocene aff. Hip. protamphibius, which is smaller and displays more advanced features (notably canine expansion and orbit elevation). In contrast, the Kanapoi material appears very similar to the material from the Hadar Formation (3.4 Ma-2.9 Ma). However, the current confusion surrounding the taxonomic status of the Hadar specimens, previously attributed to various taxa that may be identical, does not allow attribution of a specific name to the Kanapoi material for now and, while waiting for the revision of Hadar hippopotamid diversity, it is referred here to aff. Hippopotamus cf. sp. Hadar. This contribution allows recognizing that a large hippopotamid, possibly a transitional form between the late Miocene species and Plio-Pleistocene species, was distributed from Afar to Turkana between 4.2 Ma and 2.95 Ma. The marked endemism of hippopotamids in the Pleistocene rift basins therefore initiated after 2.9 Ma.


Cytochalasin B: preparation, analysis in tissue extracts, and pharmacokinetics after intraperitoneal bolus administration in mice.
Cytochalasin B (CB) was prepared by methanol extraction of dehydrated mold (Drechslera dematioidea) matte, reverse-phase C18 silica gel batch adsorption, selective elution with 1:1 (v/v) hexane:tetrahydrofuran (THF), crystallization, preparative TLC, and recrystallization. Unit gravity silica gel normal phase chromatography afforded additional CB. Yield per liter of medium was 300 mg of CB greater than 95% pure by NMR, HPLC (60:40 hexane:THF, Lichrosorb Si60 silica gel, 230 nm), and TLC. CB added exogenously to mouse organs at 1 and 5 micrograms/organ was recovered 70 to 100% by methanol extraction, adsorption to C18 silica gel Sep-Pak cartridges, elution with ethyl acetate, and analysis by TLC and/or HPLC. Limiting sensitivity (micrograms/extract) was 0.5 TLC; 1.0 HPLC. Quantitative extraction was confirmed with 3H-labeled CB. CB ip in mice at 50 mg/kg (LD10) distributed rapidly into liver, renal fat, kidney, intestines, mesentery, pancreas, spleen, and blood cells and was cleared from all but liver within 24 h. CB was below detectable levels in thymus, lymph nodes, heart, brain, bone marrow, and lungs. Cytochalasin A is fixed to tissues and not extractable. This work affords a source of CB in quantities permitting in vivo study, provides methods for extraction and analysis, and reveals the pharmacokinetics of ip bolus CB.


Spiritual practices predict migration behavior.
Each year, several thousand migrants from sub-Saharan Africa lose their lives attempting to reach Europe's southern shores. Social scientists and policymakers have puzzled over the question of why so many people are willing to take this extremely high risk of dying. Drawing on panel data from over 10,000 individuals collected over the course of 1 year in The Gambia-a country with one of the highest emigration rates in the world-we show that consulting a local healer for spiritual protection predicts migration outcomes. Furthermore, we find that spiritual practices are strongly associated with a decreased perception of one's own risk of dying on the migration journey. Our findings demonstrate the relevance of ideational factors in explaining risky migration choices, and point to spiritual leaders as important interlocutors for migration policy makers.


A novel use of 2-octyl-cyanoacrylate: controlling post-hemodialysis site hemorrhage.
A common complication of hemodialysis is bleeding from the dialysis site. To demonstrate the use of 2-octyl-cyanoacrylate in controlling venous bleeding associated with hemodialysis access. 2-octyl-cyanoacrylate is effective in stopping venous bleeding from hemodialysis sites.


Potassium transport through lipid bilayer membranes facilitated by tentoxin dimers. A new mechanism of ion carrier transport?
The cyclic tetrapeptide tentoxin at concentrations greater than 5 X 10(-7) M selectively increases the ion conductivity for potassium of lipid bilayer membranes, while the naturally occurring derivative dihydrotentoxin has no influence on this property. Current-voltage curves, zero-current potential and charge-pulse measurements were used to characterize the action of tentoxin. The results suggest that a new mechanism of facilitated ion transport operates. The model of tentoxin dimerization and tentoxin-K+ association developed is in contradiction to the model of tentoxin pore formation described recently by Heitz et al. (Biophys. Chem. 23 (1986) 245).


[The effect of antrectomy or total gastrectomy on calcium-induced gastrin secretion and gastrin release in man (author's transl)].
The effect of induced hypercalcemia on serum gastrin concentrations, measured by radioimmunoassay, and gastric acid secretion was studied in 20 healthy subjects, 8 patients after antrectomy and gastroduodenostomy (Billroth I), 12 patients after antrectomy and gastrojejunostomy (Billroth II) and in 9 patients after total gastrectomy and esophagojejunostomy. In normal man calcium stimulates gastric secretion and gastrin release. After antrectomy gastric secretion is still stimulated by calcium without changing serum gastrin levels. After total gastrectomy basal serum gastrin concentration is further reduced; calcium does not liberate gastrin. These results show that calcium-induced gastric secretion is caused by direct action at the parietal cell level besides the gastrin release from the antrum. In man, extra antral gastrin cannot be released by induced hypercalcemia.


Identification of the coding sequence for a reverse transcriptase-like enzyme in a transposable genetic element in Drosophila melanogaster.
The largest group of transposable elements in Drosophila melanogaster, copia-like elements, share some important structural features with and are intimately related in evolution to vertebrate retroviruses. To further clarify the relationship between retroviruses and copia-like transposable elements, we set out to determine the complete nucleotide sequence of the genome of 17.6, which has long terminal repeats homologous in nucleotide sequence to those of avian leukaemia-sarcoma virus. We report here that 17.6 contains three long open reading frames comparable with gag, pol and env genes in retrovirus. At the level of amino acid sequence, the longest open reading frame of 17.6 includes a coding sequence similar to that for reverse transcriptase, suggesting a role for this enzyme in the life cycle of some Drosophila copia-like elements, analogous to the situation in retrovirus.


A proposed clinical conceptual model for the physiotherapy management of Complex Regional Pain Syndrome (CRPS).
There are no validated clinical models to show a reliable pathway of guaranteeing an effective recovery for Complex Regional Pain Syndrome (CRPS) with physiotherapy management. An array of medical, psychological and physiotherapy intervention methods show weak benefit. Spearman correlations, with significance p < 0.05, from an observational, prospective, longitudinal, multi-centre study of regional standard physiotherapy CRPS management showed complete recovery to be potentially associated with baseline factors of: better mental health; better functional ability and quality of life; higher scores of extraversion personality trait; lower scores of intraversion personality trait; and interventions such as concurrent prescription of the anticonvulsant secondary analgesia group and a higher intensity of physiotherapy education intervention. These correlations were integrated with the literature evidence and the crux of previously suggested models to conceptualise a clinical model that can contribute to the broader knowledge of physiotherapy management in CRPS that should be tested with future research.


Maxillary stability after Le Fort I osteotomy using three different plate systems.
The purpose of this study was to compare postoperative changes in maxillary stability after Le Fort I osteotomy in three groups: with an unsintered hydroxyapatite (u-HA)/poly-L-lactic acid (PLLA) plate; a PLLA plate; and a titanium plate. Subjects comprised 60 Japanese patients diagnosed with mandibular prognathism. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy. All patients were randomized in groups of 20 to a u-HA/PLLA group, a PLLA plate group and a titanium plate group. Changes in postoperative time intervals between the plate groups were compared using lateral and posteroanterior cephalography. The uHA/PLLA group had significantly larger values than the PLLA group regarding change of mx1-S perpendicular to SN between 3 and 12 months (T3) (P=0.0269). The uHA/PLLA group had a significantly larger value than the PLLA group regarding change of S-A perpendicular to SN between baseline and 1 month (T1) (P=0.0257). There was no significant difference in the other measurements. This study suggests that maxillary stability with satisfactory results could be obtained in the u-HA/PLLA, PLLA plate and titanium plate groups, although there was a slight difference between the u-HA/PLLA and PLLA plate systems in Le Fort I osteotomy.


Design of a cluster-randomized trial of the effectiveness and cost-effectiveness of metformin on prevention of type 2 diabetes among prediabetic Mexican adults (the PRuDENTE initiative of Mexico City).
Type 2 diabetes (T2D) is a global epidemic, and nations are struggling to implement effective healthcare strategies to reduce the burden. While efficacy studies demonstrate that metformin can reduce incident T2D by half among younger, obese adults with prediabetes, its real-world effectiveness are understudied, and its use for T2D prevention in primary care is low. We describe the design of a pragmatic trial to evaluate the incremental effectiveness of metformin, as an adjunct to a simple lifestyle counseling. The "Prevención de la Diabetes con Ejercicio, Nutrición y Tratamiento" [Diabetes Prevention with Exercise, Nutrition and Treatment; PRuDENTE, (Spanish acronym)] is a cluster-randomized trial in Mexico City's public primary healthcare system. The study randomly assigns 51 clinics to deliver one of two interventions for 36 months: 1) lifestyle only; 2) lifestyle plus metformin, to 3060 patients ages 30-65 with impaired fasting glucose and obesity. The primary endpoint is incident T2D (fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%). We will also measure a range of implementation-related process outcomes at the clinic-, clinician- and patient-levels to inform interpretations of effectiveness and enable efforts to refine, adapt, adopt and disseminate the model. We will also estimate the cost-effectiveness of metformin as an adjunct to lifestyle counseling in Mexico. Findings from this pragmatic trial will generate new translational knowledge in Mexico and beyond, both with respect to metformin's real-world effectiveness among an 'at-risk' population, and uncovering facilitators and barriers to the reach, adoption and implementation of metformin preventive therapy in public primary care settings. This trial is registered at Clinicaltrials.gov (NCT03194009).


Chronic oesophageal foreign body in a cat.
An 11-year-old cat was presented with an approximately 2-month history of dysphagia, intermittent regurgitation and weight loss. An oesophageal foreign body was identified on plain radiographs, and an oesophagotomy was performed to remove a large V-shaped bone from the caudal cervical oesophagus. A gastrostomy feeding tube was placed to allow nutritional support postoperatively. Medical treatment for oesophagitis was initiated after surgery. No complications were encountered and the cat was discharged 4 days after surgery.


Prospective randomized study of a protein-based tissue adhesive used as a hemostatic and structural adjunct in cardiac and vascular anastomotic repair procedures.
The purpose of this study was to determine whether adjunctive use of the bovine serum albumin and glutaraldehyde tissue adhesive BioGlue (BioGlue Surgical Adhesive; CryoLife, Inc) could reduce the rate of anastomotic bleeding in patients undergoing cardiac and vascular repair procedures when compared with a standard repair control. This was a prospective multicenter, randomized, controlled clinical trial conducted in accordance with the IRB at each participating institution. A total of 151 patients consented to participation and were randomly assigned to standard repair plus BioGlue (n = 76) or standard repair alone (n = 75). These two groups were statistically homogeneous for age, gender, race, procedure, and number of anastomoses. Patients underwent cardiac procedures (n = 49), aortic procedures (n = 105), or peripheral vascular procedures (n = 48). Anastomotic bleeding was significantly reduced in the BioGlue group (18.8% of anastomoses) compared with the control group (42.9% of anastomoses, p < 0.001). Pledget use was reduced in the BioGlue group (26.2%) compared with the control group (35.9%, p = 0.047). Days in the ICU and total days in the hospital were slightly higher in the control group. Adverse event profiles were equivalent between the two groups except for occurrence of neurological defects, which were threefold less in the BioGlue group (p = 0.009). This study demonstrates that using BioGlue as an adjunct to standard repair methods is safe and significantly reduces the occurrence of intraoperative anastomotic site bleeding in cardiac and vascular repair patients. Using BioGlue along suture lines reinforces anastomoses, thus minimizing pledget use.


Is phase locking crucial to improve hearing thresholds in tinnitus patients?
Temporal processing of auditory data plays a crucial role in our proposed model of tinnitus development through stochastic resonance (SR). The model assumes a physiological mechanism optimizing auditory information transmission (as quantified by autocorrelation [AC] analysis) into the brain by adding the optimal amount of neuronal noise to otherwise subthreshold signals. We hypothesize that this takes place at the second synapse of the auditory pathway in the dorsal cochlear nucleus (DCN). We propose that after hearing loss, this neuronal noise is increased in the affected frequency band to improve hearing thresholds at the cost of upward propagation of this added noise, which finally may be perceived as tinnitus. We already showed the improvement of hearing thresholds in a large population of patients. Until now, we did not investigate the differences in hearing thresholds based on the biological constraints of early auditory temporal processing (phase locking) that is only possible up to frequencies of 5 kHz. In this report, we grouped our patient database (N = 47,986) according to tinnitus pitch (TP) of below (TP<5kHz ) or above (TP>5kHz ) the 5 kHz limit or having no tinnitus (NT) and compared their mean audiograms. We found that TP<5kHz patients showed significantly better hearing thresholds than all other patient groups independent of age. No improvement was seen for TP>5kHz patients who even showed worse thresholds than NT patients for high frequencies. These results are further evidence for our SR model of tinnitus development and the existence of AC analysis at the level of the DCN.


Microleakage of Class V composite restorations placed with etch-and-rinse and self-etching adhesives before and after thermocycling.
To evaluate the sealing ability of etch-and-rinse and self-etching adhesives in Class V cavities before and after thermocycling in vitro. Etch-and-rinse adhesives (Prime & Bond NT [P&B], XP Bond [XPB], Scotchbond 1 XT [SBX], Syntac [SYN]) and self-etching adhesives (Xeno III [XNO], i-Bond [IBO], Clearfil SE Bond [CLF]) were used. A microleakage test was performed to evaluate marginal sealing. Seventy molars were divided into seven groups according to the adhesive used. Class V cavities were restored and each group was divided into two subgroups. One group was water immersed for 24 h and the other was thermocycled. Then, specimens were immersed in fuchsin and sectioned. Microleakage and dentin permeability were recorded on occlusal and gingival walls and data were statistically analyzed. Etch-and-rinse adhesives provided perfect occlusal sealing. Self-etching adhesives obtained slight occlusal leakage. In the gingival wall, XNO and CLF showed the lowest leakage, followed by XPB and SBX, then P&B. SYN and IBO exhibited the highest leakage. All SE adhesives and XPB provided sealed dentinal tubules. Thermocycling did not affect the occlusal sealing but reduced the gingival sealing when P&B, SYN, XNO, CLF, and IBO were used. In enamel, marginal leakage was prevented when phosphoric acid was used. Self-etching adhesives promoted slight occlusal leakage. The gingival sealing was poorer than the occlusal sealing. XNO, CLF followed by XPB obtained the best gingival sealing. Thermocycling did not affect the occlusal bonding but reduced the gingival sealing, except when XPB and SBX were used.


Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection.
Staphylococcus aureus is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intracellular pathogen, we dissected their interactions over 4 days by mass spectrometry. Additionally, we investigated the dynamics of infection through live cell imaging, immunofluorescence and electron microscopy. The results highlight a major role of often overlooked temporal changes in the bacterial and host metabolism, triggered by fierce competition over limited resources. Remarkably, replicating bacteria reside predominantly within membrane-enclosed compartments and induce apoptosis of the host within ∼24 h post infection. Surviving infected host cells carry a subpopulation of non-replicating bacteria in the cytoplasm that persists. Altogether, we conclude that, besides the production of virulence factors by bacteria, it is the way in which intracellular resources are used, and how host and intracellular bacteria subsequently adapt to each other that determines the ultimate outcome of the infectious process.


Medication reconciliation to solve discrepancies in discharge documents after discharge from the hospital.
When patients are admitted to, and discharged from hospital there is a high chance of discrepancies and errors occurring during the transfer of patients' medication information. This often causes drug related problems. Correct and fast communication of patients' medication information between community pharmacy and hospital is necessary. To investigate the number, type, and origin of discrepancies within discharge documents and between discharge documents and information in the pharmacy computer system, concerning the medication of patients living independently when they are discharged from hospital. Second, to test which variables have an impact on the number of discrepancies found and to study the time spent on the medication reconciliation process. One quality-certified community pharmacy in the Netherlands. Pharmacists reviewed discharge documents of patients discharged over one year. This information was compared to information available in the pharmacy computer system. Discrepancies were discussed with medical specialists and/or general practitioners. Type and origin of discrepancies were classified. Differences in variables between hospitals were tested using Independent-Samples Mann-Whitney U Test and Pearson Chi Square test. Poisson regression analysis was performed to test the impact of variables on the number of discrepancies found. Number, type and origin of discrepancies for all independently living patients discharged from the hospital. During the study period, 100 discharges took place and were analyzed. No differences were found between the two main hospitals, a university hospital and a teaching hospital. In total, 223 discrepancies were documented. Sixty-nine discharges (69.0 %) required consultation with a patients' medical specialist. A majority of the discrepancies (73.1 %) have their origin in hospital information. The number of discrepancies found increased with the number of medicines prescribed at discharge. The community pharmacist spent, on average, 45 min on the medication review after discharge. This included 11 min for counseling the patient. Many discrepancies were found between different information sources at patient discharge from hospital. A majority of the discrepancies had their origin in hospital information. The number of medicines after discharge was related to the number of discrepancies found. The medication reconciliation process took an average of 45 minutes per patient.


Analysis of molecular species of peroxide adducts of triacylglycerols following treatment of corn oil with tert-butyl hydroperoxide.
We recently demonstrated that exposure of synthetic mono- and diunsaturated triacylglycerols to tert-butylhydroperoxide (TBHP) leads to formation of stable adducts of the oxidizing agent and the unsaturated esters (Sjövall, O., Kuksis, A., and Kallio, H., Reversed Phase High-Performance Liquid Chromatographic Separation of tert-Butyl Hydroperoxide Oxidation Products of Unsaturated Triacylglycerols, J. Chromatogr. A 905, 119-132, 2001). In the present study we isolated and identified the TBHP adducts of corn oil triacylglycerols. The much wider range of molecular species available in the corn oil permitted us to demonstrate that the yield of the adducts varies with the degree of unsaturation of the triacylglycerol. The highest yields were obtained for the linoleate (20%, of linoleoyl-containing residual triacylglycerols) and the lowest ones for the oleate (5% of oleoyl-containing residual triacylglycerols) triacylglycerols, whereas the saturated triacylglycerols did not give TBHP adducts in readily detectable amounts. Normal-phase thin-layer chromatography along with reversed-phase high-performance liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization was used to isolate and separate the major molecular species of polyunsaturated triacylglycerols and corresponding TBHP adducts. As an extreme example, the dilinoleoylmonooleoylglycerol was identified as the mono-, di-, tri-, tetra-, and penta-TBHP adduct. LC/MS with electrospray ionization at elevated capillary exit voltage (pseudo tandem mass spectrometry) was used to confirm structures of the [M-RCOOH]+ ions and the absence of TBHP adducts of [M-RCOOH]+. It is concluded that stable adduct formation is an unavoidable complication of preparation of oxotriacylglycerols by oxidation with concentrated TBHP solutions and care must be taken to resolve the adducts from the desired oxidation product.


Disease profile of 400 institutionalized mentally retarded patients in Kuwait.
In this preliminary report we summarize the results of a 4-year multidisciplinary systematic, etiological clinicogenetic survey of 400 institutionalized mentally retarded patients in Kuwait. All had an intelligence quotient below 50. A constitutional disorder, as the direct cause of the mental retardation, was found in 203 patients (50.75%)): a chromosomal abnormality in 37 (9.25%), Mendelian disorders in 137 (34.25%), MCA/MR in 22 (5.55%) and CNS malformations in 7 cases (1.75%). In 157 patients (39.35%) a pre-, peri or postnatal cause was ascertained. No etiological diagnosis was detected in 40 patients (10%). A detailed analysis of the "disease profile" is given and compared with the results of previous diagnostic genetic surveys among different institutionalized mentally retarded populations in Western and developing countries.


Specific destruction of human endothelial cell monolayers by anti-DRw antisera.
Human endothelial cells were separated by collagenase digestion from the umbilical vein of newborns. The cytotoxic effect of antisera against HLA-DRw antigens was tested on monolayers of endothelial cells, using a 51Cr retention microcytotoxicity assay in the presence of rabbit complement. Of the endothelial monolayers tested, significant concordance between the typing results obtained using cord blood-derived B lymphocytes and endothelial cell monolayers was observed. A rabbit anti-human polyspecific B cell antiserum was also capable of completely lysing the endothelial monolayers tested. In addition, 51Cr-labelled dissociated endothelial cells were lysed by nonimmune peripheral blood mononuclear cells in the presence of DRw antisera having a specificity for the target endothelium.


A binary hydrogen bonding motif based on homochiral recognition: crystal structures and hydrogen bonding networks of meso-(R,S)-bis(trifluorolactate)s.
A series of meso-compounds incorporating both enantiomers of a trifluorolactate constructed two-dimensional supramolecular sheets via homochiral hydrogen bonding chains as a binary hydrogen bonding motif.


Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum: a detailed morphological study.
In indomethacin-induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle. This study sought to substantiate light microscopic observations using three-dimensional imaging of early villous architectural changes in response to indomethacin. At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon-ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy. In indomethacin-dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss; at 6 h, the mucosa was flattened, often with epithelial loss to expose a 'contracted' villous core. Examination of the 'vasculature in carbon-injected tissues indicated significant reductions of both mucosal height and inter-capillary distance at both 2 and 6 h post-indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues. Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti-inflammatory drugs.


Correction to: Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.
Following publication of the original article [1], one of the authors has highlighted an xml-related discrepancy concerning the author group titled 'Additional Tracking Resistance to Artemisinin Collaboration authors (TRAC Group Authorship)', listed under the Acknowledgements section.


Stroke-related risk factors during pregnancy in women who underwent metabolic and bariatric surgery compared with women who have not undergone metabolic and bariatric surgery.
Stroke during pregnancy is rare, occurring in 30 of 100,000 pregnancies and accounting for 7% of maternal deaths in the United States from 2016 to 2018. Metabolic and bariatric surgery (MBS) has been shown to reduce symptoms of chronic conditions that are risk factors for stroke, including hypertension, hypercholesterolemia, and diabetes in women. However, little is known about the impact of MBS on stroke risk during pregnancy. To examine stroke and stroke risk factors including preeclampsia, eclampsia, gestational hypertension, and embolism/thrombosis in women of reproductive age who have had MBS. We used the National Inpatient Sample, a publicly available data set from the Healthcare Cost and Utilization Project that samples 20% of hospital discharges in the United States. This cross-sectional study included women between the ages of 20 and 44 years who had a maternal admission code. Weighted logistic regression was conducted to assess the odds of stroke and stroke risk factors in women with a history of MBS compared with other women of reproductive age. Women with a history of MBS have 12% lower adjusted odds of developing preeclampsia/eclampsia and 10% lower adjusted odds of gestational hypertension than women who did not undergo MBS. When stratified by race, the difference was significant in White women (preeclampsia/eclampsia: adjusted odds ratio [aOR] = .89; 95% confidence interval [CI], .81-.98; gestational hypertension: aOR = .91; 95% CI, .83-1.00). Latinas with MBS had significantly lower odds of preeclampsia/eclampsia (aOR = .75; 95% CI, .64-.90). MBS helps women lose weight and decrease the incidence of some pregnancy-related risk factors for stroke. However, there is a notable racial health disparity.


Association of FAS -1377 G>A and FAS -670 A>G functional polymorphisms of FAS gene of cell death pathway with recurrent early pregnancy loss risk.
Apoptosis during the early stages of pregnancy enables the remodeling of the uterus for proper placentation. Apoptosis in the maternal activated cytotoxic T lymphocytes allows maternal immune tolerance to pregnancy and in glandular and stromal cells it helps with trophoblastic endometrial invasion. FAS gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered FAS expression may result in altered apoptosis and ultimately affects both immune response and implantation. FAS -1377 G>A and FAS -670 A>G functional polymorphisms in the promoter region of FAS gene modulate its expression at transcriptional level. In a case-control study the contribution of FAS -1377 G>A and FAS -670 A>G polymorphisms to the risk of recurrent early pregnancy loss (REPL) was evaluated. DNA from 134 cases with a history of three or more REPL and 124 healthy controls with successful pregnancy outcomes were genotyped through PCR-RFLP. DNA sequencing was used to ascertain PCR-RFLP results. The genotype and allele frequencies for FAS -1377 G>A and FAS -670 A>G polymorphisms were compared in REPL and controls. FAS -1377 AA and AG genotypes were associated with an increased risk of REPL (OR, 3.25; 95%CI, 1.52-6.98 and OR, 2.62; 95%CI, 1.48-4.64, respectively), whereas FAS -670 genotypes conferred no risk. The -1377 AA/-670 GG genotypes combination of FAS polymorphisms showed highest risk (OR, 8.15; 95%CI, 2.75-25.81). Genotype combinations -1377 GA/-670 AA and -1377 GA/-670 AG were also statistically significant, suggestive of their role in REPL risk.


[Changes in the ultrastructure of cortical synapses during exposure to associated neurochemical stimuli].
Dependence of changes in the postsynaptic density, active zone and synaptic cleft on time relations between the administered associated stimuli was established. Locally applied glutamate and acetylcholine were used as the stimuli.


Molecular Basis of S100A1 Activation at Saturating and Subsaturating Calcium Concentrations.
The S100A1 protein mediates a wide variety of physiological processes through its binding of calcium (Ca(2+)) and endogenous target proteins. S100A1 presents two Ca(2+)-binding domains: a high-affinity "canonical" EF (cEF) hand and a low-affinity "pseudo" EF (pEF) hand. Accumulating evidence suggests that both Ca(2+)-binding sites must be saturated to stabilize an open state conducive to peptide recognition, yet the pEF hand's low affinity limits Ca(2+) binding at normal physiological concentrations. To understand the molecular basis of Ca(2+) binding and open-state stabilization, we performed 100 ns molecular dynamics simulations of S100A1 in the apo/holo (Ca(2+)-free/bound) states and a half-saturated state, for which only the cEF sites are Ca(2+)-bound. Our simulations indicate that the pattern of oxygen coordination about Ca(2+) in the cEF relative to the pEF site contributes to the former's higher affinity, whereas Ca(2+) binding strongly reshapes the protein's conformational dynamics by disrupting β-sheet coupling between EF hands. Moreover, modeling of the half-saturated configuration suggests that the open state is unstable and reverts toward a closed state in the absence of the pEF Ca(2+) ion. These findings indicate that Ca(2+) binding at the cEF site alone is insufficient to stabilize opening; thus, posttranslational modification of the protein may be required for target peptide binding at subsaturating intracellular Ca(2+) levels.


Short term relief of multisite chronicpain with Bowen Therapy: A double-blind, randomized controlled trial.
Bowen Therapy, a form of soft tissue manipulation, is commonly used to treat musculoskeletal conditions; yet, there is little evidence for its efficacy. The goal of the study was to investigate the impact of Bowen Therapy on pain and function in people with chronic pain in multiple locations. Additionally, we examined the mechanisms of effect through monitoring the nociceptive and autonomic nervous systems. The study was a double-blind, randomized controlled trial involving 31 people with chronic pain. Participants were randomized into real and sham therapy groups. Each group received 6 sessions of therapy over 8 weeks. The primary outcome measures of pain and function were assessed using standard questionnaires. Quantitative sensory testing was used to assess the nociceptive system, while recordings of heart rate variability and skin conductance were used to assess the autonomic nervous system. Outcome measures were assessed at baseline and at 1- and 6-weeks following completion of the intervention. The real therapy group had a significantly lower pain score 1-week following the intervention compared to the sham group. There were no differences between groups at the final follow-up or in the function measures. There was no significant change in the nociceptive measures but there was evidence of increased activation of the sympathetic nervous system. Bowen Therapy gave rise to a short-term reduction in pain that was not evident in a sham therapy group. The mechanisms of action of Bowen Therapy remain uncertain but may involve sympathoexcitation.


Spinal cord compression secondary to extramedullary hematopoiesis in thalassemia intermedia.
Extramedullary hematopoiesis associated with thalassemia causing spinal cord compression is an extremely rare event in the course of the disease. Documentation with an imaging technique, such as MRI, is mandatory. A patient with thalassemia intermedia, who developed paraparesis in spite of transfusion, underwent surgical decompression. Rapid neurological improvement was observed postoperatively and this neurological condition was protected with adequate hemoglobin level. Management of these patients remains controversial. Various modes of therapy such as surgical decompression, radiotherapy, and transfusion are discussed and the related literature is reviewed.


Effects of non-steroidal estrogen diethylstilbestrol on pH and ion transport in the mantle epithelium of a bivalve Anodonta cygnea.
Freshwater bivalves are used as sentinel organisms to detect pollutants effects in the aquatic environment due to their sedentary nature, filter-feeding behaviour. We aimed to determine the in vivo, ex vivo and in vitro influence of Diethylstilbestrol (DES), a widely used synthetic non-steroidal estrogen and endocrine disruptor, in Anodonta cygnea shell growth mechanisms. For that, in vivo exposure to DES (0.75μM) during 15 days, in vitro and ex vivo exposure of outer mantle epithelium (OME) cells to DES (0.75μM), were performed followed by study of short-circuit current (Isc), transepithelial potential (Vt) and transepithelial conductance (Gt) as well as identification of membrane transport systems and intracellular pH (pHi). Our results show that in vivo exposure to DES decreases in 30% the OME Isc and ex vivo addition of DES to the basolateral side of OME also induced Isc decrease. Several membrane transporters such as V-type ATPases, Na(+)/H(+) exchangers, Na(+)-K(+) pump, Na(+)-driven and Na(+)-independent HCO3(-)/Cl(-) transporters and Na(+)/HCO3(-) co-transporter were identified as responsible for pHi maintenance in OME and noteworthy, DES caused a pHi decrease in OME cells similar to the effect observed when OME cells were exposed to 4,4'-diisothiocyanostilbene disulfonic acid (DIDS), an inhibitor of several bicarbonate membrane transporters. The addition of DIDS after OME cells exposure to DES did not cause any alteration. We concluded that DES is able to modulate membrane ion transport and pHi in the OME of A. cygnea and that this effect seems to be due to inhibition of HCO3(-)/Cl(-) co-transporters present on the basolateral membrane.


Therapeutic response after first month of tadalafil treatment predicts 12 months treatment continuation in patients with erectile dysfunction: results from the DETECT study.
The DETECT study is a prospective, 12-month, European, multicenter, observational study of patients with erectile dysfunction (ED) initiating or changing treatment to tadalafil in routine clinical practice. To determine the effectiveness of tadalafil and the factors associated with the continuation of treatment for ED at 12 months. The DETECT study included 1,900 men aged 18 years and older with a history of ED and who were initiating or changing treatment to tadalafil. Sexual function at baseline, 1, 6, and 12 months was assessed using the International Index of Erectile Function-erectile function (IIEF-EF) domain. Factors associated with treatment continuation at 12 months were evaluated using multivariate regression analysis. At 12 months, 1,319 (84%) of 1,567 patients who completed the questionnaire reported continued use of tadalafil. Among these patients, tadalafil was highly effective: 94%, 95%, and 71% with severe, moderate, and mild ED at baseline, respectively, improved by at least one IIEF-EF category and 65% had normal EF. Five factors were associated with tadalafil continuation at 12 months: (i) ED severity at 1 month (based on IIEF-EF domain score); (ii) tolerance to treatment at 1 month; (iii) age younger than 60 years; (iv) number of sexual attempts in the first month; and (v) no history of pelvic surgery. Patient and partner factors at baseline were not significantly associated with continued tadalafil use. Tadalafil is an effective treatment for ED in routine clinical practice. The therapeutic response and treatment tolerance after 1-month treatment are the most important factors influencing tadalafil continuation.


Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology.
Cerebral palsy is a clinical descriptor covering a diverse group of permanent, non-degenerative disorders of motor function. Around one-third of cases have now been shown to have an underlying genetic aetiology, with the genetic landscape overlapping with those of neurodevelopmental disorders including intellectual disability, epilepsy, speech and language disorders and autism. Here we review the current state of genomic testing in cerebral palsy, highlighting the benefits for personalized medicine and the imperative to consider aetiology during clinical diagnosis. With earlier clinical diagnosis now possible, we emphasize the opportunity for comprehensive and early genomic testing as a crucial component of the routine diagnostic work-up in people with cerebral palsy.


Serum concentration of fatty acids in children with obesity and nonalcoholic fatty liver disease.
It has been suggested that circulating fatty acids (FAs) take part in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in children with obesity. The aims of this study were to evaluate the serum FA concentration in this pediatric population. The prospective study included 80 children with obesity and suspected liver disease. Patients with viral hepatitis, autoimmune, toxic, and selected metabolic liver diseases were excluded. Criteria for NAFLD diagnosis included liver steatosis in ultrasound as well as elevated alanine transaminase (ALT) serum activity. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). Fasting serum FA concentrations were measured in all children using gas-liquid chromatography. NAFLD was diagnosed in 31 children. Total FA concentration was significantly higher (P < 0.01) in all obese children as well as in obese children with NAFLD compared with controls. In children with NAFLD, a significant, positive correlation was found between total FA concentration and cholesterol (R = 0.47, P < 0.01), triacylglycerols (R = 0.78, P < 0.001), and insulin (R = 0.45, P < 0.011). In a group of children with obesity, TILC correlated positively with saturated FA concentration (R = 0.23, P < 0.05). Data from the present study do support the hypothesis that FAs are potentially involved in the pathogenesis of NAFLD in children with obesity.


A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis.
For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation.


Liver necrosis following cholecystectomy in sickle cell disease.
Postoperative vaso-occlusive disease may be a life-threatening condition in patients affected by sickle cell disease, necessitating sometimes liver transplantation. After laparoscopic cholecystectomy, liver necrosis is usually secondary to intraoperative vascular injury. In this patient, the vaso-occlusive crisis mimicked a vascular injury with segmental postoperative necrosis.


Antitumor effects of combining tumor radiation with the antivascular action of ultrasound stimulated microbubbles.
More and more evidence indicates tumor vasculature plays an important role in tumor radiation response. In this study, we investigated ultrasound stimulated microbubbles to enhance the effects of radiation. Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human bladder xenografts grown in severe combined immunodeficiency (SCID) mice were treated using microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. There existed a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.


The complete sequence of the rice (Oryza sativa) chloroplast genome: intermolecular recombination between distinct tRNA genes accounts for a major plastid DNA inversion during the evolution of the cereals.
The entire chloroplast genome of the monocot rice (Oryza sativa) has been sequenced and comprises 134525 bp. Predicted genes have been identified along with open reading frames (ORFs) conserved between rice and the previously sequenced chloroplast genomes, a dicot, tobacco (Nicotiana tabacum), and a liverwort (Marchantia polymorpha). The same complement of 30 tRNA and 4 rRNA genes has been conserved between rice and tobacco. Most ORFs extensively conserved between N. tabacum and M. polymorpha are also conserved intact in rice. However, several such ORFs are entirely absent in rice, or present only in severely truncated form. Structural changes are also apparent in the genome relative to tobacco. The inverted repeats, characteristic of chloroplast genome structure, have expanded outward to include several genes present only once per genome in tobacco and liverwort and the large single copy region has undergone a series of inversions which predate the divergence of the cereals. A chimeric tRNA pseudogene overlaps an apparent endpoint of the largest inversion, and a model invoking illegitimate recombination between tRNA genes is proposed which accounts simultaneously for the origin of this pseudogene, the large inversion and the creation of repeated sequences near the inversion endpoints.


Association of oral contraceptive use with suicidal behavior among representative Korean population: Results from Korea National Health and Nutrition Examination Survey (2007-2016).
The association of suicide with the use of oral contraceptives (OC) is unknown in the Asian population. We aimed to evaluate the association of OC use and suicidal behavior in a nationally representative population of Korean women. Of the 44,501 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20 years or older who had completed information on OC use and suicidal behavior were included. Women with a history of cancer were excluded. Compared to non-users of OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a multivariable logistic regression among OC users, with testing of the interaction term of OC use and history of depression. We also conducted a stratified analysis by history of depression. A total of 4,067 women (14.0%) reported they had suicide ideations or had attempted suicide, respectively. OC use was associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00-1.24) after adjustments for age, demographic factors, age of menarche, and lifestyle behaviors. When stratified by history of depression diagnosis, ORs linearly increased as the total duration of OC use lengthened among women with a history of depression; however, women without a history of depression showed peaked OR at 4- to 12-month use. There is an increased association between OC use and suicidality and the pattern of the relationship differs depending on whether there is a history of depression.


Avoidance of Phycomyces in a controlled environment.
The sporangiophore of the fungus Phycomyces bends away from nearby objects without ever touching them. It has been thought that these objects act as aerodynamic obstacles that damp random winds, thereby generating asymmetric distributions of a growth-promoting gas emitted by the growth zone. In the interest of testing this hypothesis, we studied avoidance in an environmental chamber in which convection was suppressed by a shallow thermal gradient. We also controlled pressure, temperature, and relative humidity of the air, electrostatic charge, and ambient light. A protocol was established that yielded avoidance rates constant from sporangiophore to sporangiophore to within +/- 10%. We found that avoidance occurred at normal rates in the complete absence of random winds. The rates were smaller at 100% than at lower values of relative humidity, but not by much. Remarkably, at a distance as great as 0.5 mm, avoidance from a 30-micron diam glass fiber (aligned parallel to the sporangiophore) was about the same as that from a planar glass sheet. However, the rate for the fiber fell more rapidly with distance. The rate for the sheet remained nearly constant out to approximately 4 mm. We conclude that avoidance depends either on adsorption by the barrier of a growth-inhibiting substance or emission by the barrier of a growth-promoting substance; it cannot occur by passive reflection. Models that can explain these effects are analyzed in the Appendix.


Minimal or no cancer in radical prostatectomy specimens. Report of 13 cases of the "vanishing cancer phenomenon".
Early detection efforts identify prostate cancer at lower clinical and pathologic stages, often resulting in smaller volumes of tumor in radical prostatectomy specimens. In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma reveals minimal or no residual cancer. We evaluated the clinical and pathologic findings in 13 such cases in an effort to document this finding, which we refer to as the "vanishing cancer phenomenon." The mean number of prostate slides examined per case was 79 (range, 34-248). Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. Mean cancer volume in the 10 cases with residual tumor was 0.019 cc (range, 0.003-0.038); the largest single dimension of any tumor focus was 3 mm. All cancers were well differentiated or moderately differentiated in the biopsy and prostatectomy. Our results indicate that in some cases cancer may be extremely difficult or impossible to find in the prostatectomy specimen despite exhaustive sampling. The incidence of this "vanishing cancer phenomenon" is probably increasing because more low-stage cancers are being treated by prostatectomy. The inability to identify cancer in a prostate removed for needle biopsy-proven carcinoma may not indicate technical failure.


Biocompatibility of hydrophilic intraocular lenses.
To assess the biocompatibility of 3 hydrophilic acrylic intraocular lenses (IOLs) by evaluating the postoperative cell reaction on the IOL surface, anterior capsule opacification (ACO) rate, and presence of membrane growth over the anterior IOL surface. University Eye Clinic of Trieste, Trieste, Italy. In this prospective study, 73 patients were randomized to receive 1 of 3 types of hydrogel IOLs after phacoemulsification: Storz Hydroview H60M, Corneal ACR6D, or Ioltech Stabibag. To analyze and photograph the anterior IOL surface, slitlamp biomicroscopy and specular microscopy were performed 7, 30, 90, and 180 days after surgery. Small, epithelioid, and giant inflammatory cell reaction was evaluated. In addition, ACO and membrane growth on the anterior IOL surface were assessed. Low inflammatory cell adhesion was observed on the anterior surface of all 3 IOLs. The Stabibag group had a significantly higher grade of small inflammatory cell reaction 7 and 30 days after surgery. A significantly higher rate of ACO was observed in the ACR6D group. The Hydroview and ACR6D groups had a significantly higher percentage of membrane growth from the capsulorhexis edge onto the anterior IOL surface than the Stabibag group. Clinically, the 3 hydrophilic IOLs behaved in a different manner, showing the different forms of biocompatibility. Results indicate that a different chemical composition determines correspondingly different protein absorption on IOL surfaces. This might result in a different adhesion pattern and spreading of lens epithelial and inflammatory cells.


Tuberculosis-related choriocapillaritis (multifocal-serpiginous choroiditis): follow-up and precise monitoring of therapy by indocyanine green angiography.
To report the case of a patient initially diagnosed with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), characterized by relentless evolution despite high-dose steroid therapy. An interferon-gamma release assay (IGRA) indicated a diagnosis of suspected tuberculous choriocapillaritis and the disease responded only to massive inflammation suppressive therapy and antibiotic therapy. Case report. Review of clinical features and investigational procedures. Smoldering relentless evolution and subsequent arrest of progression could be precisely monitored by indocyanine green angiography (ICGA). The patient did not recover after standard anti-tubercolosis (TB) therapy combined with corticosteroid. A fourth antibiotic had to be added in order to stop the progression of the retinal disease. In each case of choriocapillaritis such as APMPPE an infectious cause including TB has to be excluded making IGRA tests unavoidable. As the main structure involved is the choriocapillaris the most precise follow-up or monitoring is obtained with ICGA.


Unitary Human-Environment Field Mutual Process: Knowing Participation in Patterning the Environment.
Martha E. Rogers identified people and their environment as unitary, indivisible wholes, further defining both as energy fields identified by rhythmical patterning. It is suggested that sharper focus be placed on the contribution of the environment in wellbecoming to encourage people to participate more knowingly in patterning the environmental field. Mutual rhythmical patterning involving nature and animal companions provides exemplars for discussion, which is grounded in two theories derived from Rogerian nursing science. The first is Barrett's theory of power as knowing participation in change, and the second is Phillips' theory of pandimensional awareness-integral presence, which unites Rogers' theories of accelerating change and the paranormal.


Magnetic resonance to assess the aortic valve area in aortic stenosis: how does it compare to current diagnostic standards?
The purpose of the present study was to evaluate whether magnetic resonance (MR) planimetry of the aortic valve area (AVA) may prove to be a reliable, non-invasive diagnostic tool in the assessment of aortic valve stenosis, and how the results compare with current diagnostic standards. Current standard techniques for assessing the severity of aortic stenosis include transthoracic and transesophageal echocardiography (TEE) as well as transvalvular pressure measurements during cardiac catheterization. Forty consecutive patients underwent cardiac catheterization, TEE, and MR. The AVA was estimated by direct planimetry (MR, TEE) or calculated indirectly via the peak systolic transvalvular gradient (catheter). Pressure gradients from cardiac catheterization and Doppler echocardiography were also compared. By MR, the mean AVA(max) was 0.91 +/- 0.25 cm(2); by TEE, AVA(max) was 0.89 +/- 0.28 cm(2); and by catheter, the AVA was calculated as 0.64 +/- 0.26 cm(2). Mean absolute differences in AVA were 0.02 cm(2) for MR versus TEE, 0.27 cm(2) for MR versus catheter, and 0.25 cm(2) for TEE versus catheter. Correlations for AVA(max) were r = 0.96 between MR and TEE, r = 0.47 between TEE and catheter, and r = 0.44 between MR and catheter. The correlation between Doppler and catheter gradients was r = 0.71. Magnetic resonance planimetry of the AVA correlates well with TEE and less well with the catheter-derived AVA. Invasive and Doppler pressure correlated less well than those obtained from planimetric techniques. Magnetic resonance planimetry of the AVA may provide an accurate, non-invasive, well-tolerated alternative to invasive techniques and transthoracic echocardiography in the assessment of aortic stenosis.