Identifying Young Adults at High Risk for Weight Gain Using Machine Learning.
Weight gain among young adults continues to increase. Identifying adults at high risk for weight gain and intervening before they gain weight could have a major public health impact. Our objective was to develop and test electronic health record-based machine learning models to predict weight gain in young adults with overweight/class 1 obesity. Seven machine learning models were assessed, including three regression models, random forest, single-layer neural network, gradient-boosted decision trees, and support vector machine (SVM) models. Four categories of predictors were included: 1) demographics; 2) obesity-related health conditions; 3) laboratory data and vital signs; and 4) neighborhood-level variables. The cohort was split 60:40 for model training and validation. Area under the receiver operating characteristic curves (AUC) were calculated to determine model accuracy at predicting high-risk individuals, defined by ≥ 10% total body weight gain within 2 y. Variable importance was measured via generalized analysis of variance procedures. Of the 24,183 patients (mean [SD] age, 32.0 [6.3] y; 55.1% females) in the study, 14.2% gained ≥10% total body weight. Area under the receiver operating characteristic curves varied from 0.557 (SVM) to 0.675 (gradient-boosted decision trees). Age, sex, and baseline body mass index were the most important predictors among the models except SVM and neural network. Our machine learning models performed similarly and had modest accuracy for identifying young adults at risk of weight gain. Future models may need to incorporate behavioral and/or genetic information to enhance model accuracy.


A Literature Review and Summary Recommendations of the Impact of Bariatric Surgery on Orthopedic Outcomes.
Many surgeons recommend weight loss in preparation for orthopedic procedures, yet the impact of surgically induced weight loss before orthopedic procedures is not clear. We undertook a literature review to assess the impact of bariatric surgery on the outcomes of total joint arthroplasty (TJA). We searched PubMed, Medline, Cochrane Library, and Google Scholar for studies (2010-2017) that evaluated the associations between obesity, bariatric surgery, and orthopedic surgery. Nine studies found that prior bariatric surgery decreased major and minor post-operative complications, operating room (OR) time, length of stay (LOS), risk of re-operation, and 90-day re-admissions after TJA. Two studies found that bariatric surgery patients had a higher reoperation rate for stiffness and infection as well as need for revision within 90 days after TJA. One meta-analysis found no statistically significant differences in wound infections, revisions, or mortality irrespective of bariatric surgery status; and another meta-analysis showed reduced medical complications, LOS, and OR time. Our review highlights many gaps in our knowledge and the need for additional studies to define the impact of the bariatric-first approach on TJA outcomes. We propose a framework from lessons learned to raise awareness of medical and surgical options of weight management before elective orthopedic operations in patients with obesity.


Starvation-induced decreased sensitivity of resting metabolic rate to triiodothyronine.
The decrease in resting oxygen consumption induced by starvation was found to occur not only in euthyroid rats but also in hypothyroid and even in hypothyroid animals treated with triiodothyronine. Furthermore, the effectiveness of triiodothyronine was decreased when given to hypothyroid animals.


Cytoplasmic Ca2+ release induced by microinjection of Ca2+ and effects of microinjected divalent cations on Ca2+ sequestration and exocytosis of cortical alveoli in the medaka egg.
Intracellular release of Ca2+ by microinjection of Ca2+ was analyzed by measuring the luminescence of aequorin loaded in eggs of the medaka (Oryzias latipes). Microinjection of Ca2+ into the cortical cytoplasm induced propagative waves of cytoplasmic Ca2+ release and exocytosis of cortical alveoli initiated at the injection point. The Ca2+ wave was initiated with a time lag after some was sequestered at the region of the microinjection. Microinjection of Mg2+ or Mn2+ failed to trigger Ca2+ release and exocytosis. When the aequorin-loaded eggs were inseminated after microinjection of Mg2+, Mn2+, or Co2+ into a restricted region of the vegetal hemisphere, the wave of Ca release was propagated through the injected region toward the vegetal pole, but neither Ca sequestration (fall in Ca-aequorin luminescence) nor exocytosis occurred at the area of cortex where the eggs were injected with these divalent cations. These results suggest that a significant period is required to induce Ca2+ release from cytoplasmic stores by the increased Ca2+ concentration and that both the phenomena of Ca2+ release and Ca sequestration are involved in the process of exocytosis.


Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice.
A single dose of the orexin-1 (OX1) receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5] naphthyridin-4-yl urea hydrochloride (SB-334867-A) reduces orexin-A-induced feeding and natural feeding in Sprague Dawley rats. In this study, the anti-obesity effects of SB-334867-A were determined in genetically obese (ob/ob) mice dosed with SB-334867-A (30 mg/kg, i.p.) once daily for 7 days, and then twice daily for a further 7 days. SB-334867-A reduced cumulative food intake and body weight gain over 14 days. Total fat mass gain, determined by Dual Emission X-ray Absorptiometry, was reduced, while gain in fat-free mass was unchanged. Fasting (5 h) blood glucose was also reduced at the end of the study, with a trend to reduced plasma insulin. Interscapular brown adipose tissue (BAT) weight was reduced, the tissue was noticeably darker in colour and quantitative PCR (TaqMan) analysis of this tissue showed a trend to an increase in uncoupling protein-1 mRNA expression, suggesting that SB-334867-A might stimulate thermogenesis. This was confirmed in a separate study in which a single dose of SB-334867-A (30 mg/kg, i.p.) increased metabolic rate over 4 h in ob/ob mice. OX1 receptor mRNA was detected in BAT, and its expression was increased by 58% by treatment with SB-334867-A. This is the first demonstration that OX1 receptor antagonists have potential as both anti-obesity and anti-diabetic agents.


[Single-lung transplantation for end-stage emphysema].
To evaluate operative technique, patient selection and perioperative management of single-lung transplantation for a patients with end-stage emphysema. A 56-year-old patient with end-stage emphysema underwent left-lung transplantation on September 28, 2002. The surgical technique used was similar to that mentioned in the literature. The donor lung was perfused by LPD solution with a cold ischemic time of 260 minutes. Cardiopulmonary bypass was not performed. The patient weaned from a ventilator at the 93th hour after operation. Immunosuppressants included cyclosporine, mycophenolate mofetil and corticosteroid. Acute rejection occurred on the ninth day after operation and was cured by bolus methylprednisolone given intravenously. Lung function was improved significantly and the patient was discharged from the hospital on the 47th day after operation. Single-lung transplantation for patients with end-stage emphysema is effective for long-term improvement of pulmonary function.


Host range mutants of Minute Virus of Mice with a single VP2 amino acid change require additional silent mutations that regulate NS2 accumulation.
Two host range switch mutants of the immunosuppressive strain of parvovirus Minute Virus of Mice (MVMi) were isolated from plaques on A9 fibroblasts. Both carried a single coding mutation at residue D399 in VP2, to alanine and glycine in hr105 and hr107, respectively, and a second, non-coding, guanine-to-adenine change at nucleotide 1970 in hr105 and 1967 in hr107. These mutations were recreated in a wild type MVMi infectious plasmid clone, both alone and as pairs, in either the original or switched combinations. All single mutants failed to replicate productively in fibroblasts, but the two pairs of changes were functionally equivalent. Single D399 mutations allowed the viruses to initiate infection in fibroblasts, but NS2 expression was severely restricted and correlated with poor accumulation and release of progeny virus. Mutations at 1967 or 1970 enhanced NS2 accumulation, and allowed efficient progeny production and release. Conversely, the D399 mutations destroyed the viruses' ability to infect EL4 lymphocytes. In all productive EL4 infections, NS2 was expressed at high ratios even in the absence of upstream mutations, and progeny accumulation was efficient. However, EL4 cells lack a mechanism for early progeny release, potentially explaining why virus amplification in these cells is slow.


Horseback riding: impact on sexual dysfunction and lower urinary tract symptoms in men and women.
To determine whether subjects engaged in horseback riding are more likely to be affected by sexual dysfunction and lower urinary tract symptoms than those engaged in sports with less perineal impact. Surveys evaluating the presence of and the risk factors for sexual dysfunction and urinary symptoms were distributed among members of equestrian clubs, swimming clubs, and individual horseback riders and swimmers. About 327 surveys were distributed by hand at horse shows and swimming pools. A total of 2000 surveys were sent by direct mail to random members of 1 national equestrian organization and 1 national swimming organization. We also evaluated bicycle habits as a possible confounding factor. There was no significant association between horseback riding and lower urinary tract symptoms (P = .1759) and sexual dysfunction (P = .1793) in males. The same applies to the association of horseback riding and lower urinary tract symptoms (P = .5036) and sexual dysfunction (P > .05) in females, although there was a trend toward a protective association between horseback riding and stress incontinence (P = .0567). Years of bicycling (P = .04) and hardness of the bicycle seat (P = .02) were associated with an increased prevalence for lower urinary tract symptoms in women. Regular participation in horseback riding is not significantly associated with increased prevalence of lower urinary tract symptoms or sexual dysfunction, although it may be associated with decreased prevalence of stress urinary incontinence. Bicycle riding may be associated with higher prevalence of lower urinary tract symptoms in women.


Selective modulation of the NPY receptors of the Y2 subtype by alpha 2 receptors in the nucleus tractus solitarii of the rat. A cardiovascular and quantitative receptor autoradiographical analysis.
The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection and identification of carcinogen-peptide adducts by nanoelectrospray tandem mass spectrometry.
Nanoelectrospray (nanoES) tandem mass spectrometry was used to examine covalently modified peptides in crude enzymatic digests of human serum albumin (HSA) that had been exposed to either benzo[a]pyrene diol epoxide (B[a]PDE, 1), chrysene diol epoxide (CDE, 2), 5-methylchrysene diol epoxide (5MeCDE, 3), or benzo[g]chrysene diol epoxide (B[g]CDE, 4). The low flow rates of nanoES (approximately 20 nL/min) allowed several MS/MS experiments to be optimized and performed on a single sample with very little sample consumption (approximately 30 min analysis time/microL sample). Initially, nanoES was compared with conventional LC/MS/MS analysis of carcinogen-peptide adducts. For example, nanoES analysis of an unseparated digest of B[a]PDE-treated serum albumin revealed the same peptides (RRHPY and RRHPY-FYAPE) that were previously shown, by LC/MS/MS, to be adducted with B[a]PDE. In addition, nanoES could detect unstable peptide adducts that might not otherwise have been directly observable. Finally, nanoES was shown to be an effective way to screen mixtures of modified and unmodified peptides for which no chromatographic information is available.


Late cardiac tamponade after percutaneous closure of a patent foramen ovale.
We report the case of a 35-year-old man who had a transient ischemic cerebral attack and then underwent a percutaneous closure of the patent foramen ovale (PFO) with a Cardiastar device. One year later, the patient developed a cardiac tamponade due to an important hemorrhagic pericardial effusion. Transoesophageal echocardiography showed that one of the struts had impinged on the aortic root in the region adjacent to the transverse pericardial sinus. Therefore, we speculated that the strut had passed through the aortic wall by slow erosion, leading to the pericardial effusion. Cardiac CT and subsequent surgery confirmed the perforation of the left atrial roof and the aortic root by two struts of the device. This is the first reported case of late cardiac tamponade and underscores the importance of long-term follow-up after PFO closure device implantation.


Dietary taurine intake and serum taurine levels of women on Jeju Island.
The purpose of this study was to investigate the dietary taurine intake and serum taurine levels of women on Jeju Island in Korea. Sixty six married women aged 43.5 +/- 7.1 volunteered for this study: 34 from the city area and 32 from two fishing-farming areas. Diet samples were collected from the participants; the samples included three meals (breakfast, lunch and supper), including snacks, drinks and whatever else the participants had eaten for 24 hours. Taurine levels in the diet and serum were determined as the dabsyl derivative by HPLC with a Rf-detector. The intake of taurine ranged from 8.4 to 767.6 mg/day and its mean value was 163.9 +/- 150.2 mg/day (mean +/- SD). There was a significant difference between the two groups: 114.9 +/- 78.7 for the women from the city area and 215.9 +/- 187.9 mg/day for the women from the fishing-farming areas (p<0.001). The taurine intake of the total diet, including all snacks and drinks, was 2300 +/- 584 g/day for the city area and 2342 +/- 528 g/day for the fishing-farming areas. The daily protein intake was 58.8 +/- 16.4 g for the women of the city area and 65.5 +/- 17.1 g for the women of the fishing-farming areas. There was a significant correlation between the intake of fish/shellfish and taurine (p=0.001) while there was no correlation between the intake of protein and taurine (p=0.057). The taurine levels in serum ranged from 68.6 to 261.6 micromol/L and the mean value was 169.7 +/- 41.5 micromol/L. There was no significant difference between the women from the city area and the women from the fishing-farming areas in serum taurine levels. The correlations of serum taurine levels with serum retinol levels (p=0.016) and alpha-tocopherol (p=0.014) levels were significant. These results suggest that taurine intake is dependent on the fish/shellfish intake and that taurine may play an important role in the retention of antioxidative nutrients.


Subacute oral toxicity study of diethylphthalate based on the draft protocol for "Enhanced OECD Test Guideline no. 407".
We performed a 28-day repeated-dose toxicity study of diethylphthalate based on the draft protocol of the "Enhanced OECD Test Guideline 407" to investigate whether it has endocrine-mediated properties according to this assay. Diethylphthalate was orally administered to SD rats at doses of 0, 40, 200, and 1,000 mg/kg/day for at least 28 days, but no endocrine-mediated effects were detected based on any of the parameters examined, suggesting that diethylphthalate does not possess endocrine properties according to this assay.


Erratum to: Poor prognostic factors in patients who underwent surgery for acute non-occlusive ischemic colitis.
[This corrects the article DOI: 10.1186/s13017-015-0003-z.].


Probe Design Strategies for Oligonucleotide Microarrays.
Oligonucleotide microarrays have been widely used for gene detection and/or quantification of gene expression in various samples ranging from a single organism to a complex microbial assemblage. The success of a microarray experiment, however, strongly relies on the quality of designed probes. Consequently, probe design is of critical importance and therefore multiple parameters should be considered for each probe in order to ensure high specificity, sensitivity, and uniformity as well as potentially quantitative power. Moreover, to assess the complete gene repertoire of complex biological samples such as those studied in the field of microbial ecology, exploratory probe design strategies must be also implemented to target not-yet-described sequences. To design such probes, two algorithms, KASpOD and HiSpOD, have been developed and they are available via two user-friendly web services. Here, we describe the use of this software necessary for the design of highly effective probes especially in the context of microbial oligonucleotide microarrays by taking into account all the crucial parameters.


Hidden Genetic Regulation of Human Complex Traits via Brain Isoforms.
Alternative splicing exists in most multi-exonic genes, and exploring these complex alternative splicing events and their resultant isoform expressions is essential. However, it has become conventional that RNA sequencing results have often been summarized into gene-level expression counts mainly due to the multiple ambiguous mapping of reads at highly similar regions. Transcript-level quantification and interpretation are often overlooked, and biological interpretations are often deduced based on combined transcript information at the gene level. Here, for the most variable tissue of alternative splicing, the brain, we estimate isoform expressions in 1,191 samples collected by the Genotype-Tissue Expression (GTEx) Consortium using a powerful method that we previously developed. We perform genome-wide association scans on the isoform ratios per gene and identify isoform-ratio quantitative trait loci (irQTL), which could not be detected by studying gene-level expressions alone. By analyzing the genetic architecture of the irQTL, we show that isoform ratios regulate educational attainment via multiple tissues including the frontal cortex (BA9), cortex, cervical spinal cord, and hippocampus. These tissues are also associated with different neuro-related traits, including Alzheimer's or dementia, mood swings, sleep duration, alcohol intake, intelligence, anxiety or depression, etc. Mendelian randomization (MR) analysis revealed 1,139 pairs of isoforms and neuro-related traits with plausible causal relationships, showing much stronger causal effects than on general diseases measured in the UK Biobank (UKB). Our results highlight essential transcript-level biomarkers in the human brain for neuro-related complex traits and diseases, which could be missed by merely investigating overall gene expressions. The online version contains supplementary material available at 10.1007/s43657-023-00100-6.


Liquid-liquid microextraction based on a dispersion of Pd nanoparticles combined with ETAAS for sensitive Hg determination in water samples.
A novel and highly efficient microextraction methodology based on the use of palladium nanoparticles (Pd NPs) was developed for the preconcentration and determination of Hg in water samples. Selective separation of the analyte was achieved by application of dodecanethiolate-coated Pd monolayer-protected clusters (C12S Pd MPCs) in a liquid-liquid microextraction technique (LLME). A volume of 20 μL of toluene phase containing C12S Pd MPCs was used for extraction and final phase was injected in an electrothermal atomic absorption spectrometer (ETAAS) for Hg detection. The effects of different variables, such as sample volume, extraction time, and NPs dispersion volume were carefully studied. A sensitivity enchancement factor of 95 was obtained under optimal experimental conditions. Furthermore, low detection limit (7.5 ng L(-1)) and good precision (relative standard deviation of 4.1% at 0.25 μg L(-1) Hg and n=10) were achieved. The proposed method can be considered as a rapid, cost-effective, and efficient alternative for Hg determination in water samples like river, lake, mineral and tap water.


Risk factors associated with post-extubation stridor in the trauma intensive care unit.
Post-extubation stridor is an uncommon complication in medical intensive care units (ICUs) but has not been well studied in trauma patients. We sought to determine the incidence of reintubation due to stridor in trauma patients and describe associated risk factors. A retrospective review of all intubated trauma patients was performed. Data collected included presence of stridor, demographic data, and details of intubation and extubation. Of all trauma patients reintubated, 31% were for stridor. Although female gender, age less than 18, blunt mechanism, and duration of intubation 5 days or more were associated with reintubation for stridor, endotracheal tube diameter was not. Mortality was not increased with reintubation. Trauma ICU patients are reintubated for stridor at a higher rate than medical ICU patients. Age, gender, blunt mechanism, and duration of intubation are risk factors for this complication.


A study on the mechanism of Indium phosphide/zinc sulfide core/shell quantum dots influencing embryo incubation of rare minnow (Gobiocypris rarus).
Quantum dots (QDs) inhibit fish hatching, but the mechanism is still unclear. In this study, the effect of Indium phosphide/zinc sulfide quantum dots (InP/ZnS QDs) on the embryo incubation of rare minnow was investigated. Five experimental concentration groups were set up according to the preliminary experimental results, which were 0, 50, 100, 200 and 400 nM. A direct exposure method was adopted to expose embryos to InP/ZnS QDs solution. The results showed that InP/ZnS QDs significantly inhibited the embryo hatching rate, delayed embryo emergence, affected the expression of genes associated with hatching gland cells and hatching enzymes. InP/ZnS QDs also destroy the structure of the embryo chorion. In addition, QDs can cause oxidative stress in embryos. Transcriptional sequencing analysis showed that InP/ZnS QDs InP/ZnS QDs may have induced the production of a hypoxic environment and triggered induce abnormal cardiac muscle contraction, inflammatory response and apoptosis process in embryos. In conclusion, QDs influences embryo hatchability largely through egg chorion mediation.


Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review.
This short review describes a series of case-control studies on the concentration and oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Down's syndrome (DS). The same parameters were re-examined in the PD patients 5 years later. The specific oxidative activity (oxidative activity related to mass) of CP was calculated in PD and DS. In AD and PD the oxidative activity of CP and SOD1 activity was significantly lower in patients than controls. The specific oxidative activity of CP was also significantly lower in PD patients. The difference in all parameters determined was still present 5 years later in PD patients. There was no difference in the concentration or activity of CP in patients with DS and controls. Because of the gene-dose effect (the gene for SOD1 is located on chromosome 21); the SOD1 activity was 50% higher in the patients than the controls. The CP specific oxidative activity and SOD1 activity were found to be significantly lower in the older (>40 years) than the younger DS patients. Whether changes in CP and SOD1 in AD, PD and DS are primary changes or a result of prolonged disease burden needs to be examined.


Parent Perspectives on Family-Based Psychosocial Interventions for Congenital Heart Disease.
To identify parents' preferences for goals and structure of intervention programs to support the psychosocial needs of families impacted by congenital heart disease (CHD). Information about parent priorities for psychosocial programs was obtained in this mixed-methods study conducted at a pediatric hospital in the Mid-Atlantic region of the US. Participants were parents (N = 34; 20 mothers, 14 fathers) of children with CHD between the ages of 1 and 3 years who had cardiac surgery at less than 6 months of age. Qualitative data were excerpts from semistructured interviews. Quantitative data were participant choices regarding their ideal psychosocial program resulting from a card sort. Parents reported that psychosocial interventions should support partnership in their child's care, promote self-care, facilitate communication with providers, prepare parents for challenges after hospitalization, provide education about child neurodevelopment, and help parents engage social support. Parents reported needing formalized support across care, brief intervention models, in-person individualized or small group support, and involvement of multidisciplinary providers and peer mentors in the delivery of interventions. Parents of children with CHD need psychosocial interventions that empower them to act as primary caregivers and effective advocates for their child. Individualized, formalized, and multidisciplinary approaches to psychosocial care are necessary to best accommodate the dynamic stressors related to parenting a child with CHD and may mitigate the impact of parent mental health problems on child outcomes.


Drying Induced Impact on Composition and Oil Quality of Rosemary Herb, Rosmarinus Officinalis Linn.
The natural drying of Rosmarinus officinalis Linn. herbs severely affects its volatile oil quality and yields, which is reported here for the first time. The oils obtained through hydrodistillation from fresh, one, two, and three-weeks dried herbs were analyzed by gas chromatography-mass spectroscopy (GC-MS) and gas chromatography-flame ionization detector (GC-FID), and the yields were 198 ± 3.45, 168.7 ± 5.11, and 97.8 ± 1.27 mg, respectively, as compared to the internal referral standard of 327 ± 5.91 mg yield of the one-week dried herbs' oil. Camphor, the major constituent, significantly depleted from 20.96% to 13.84%, while bornyl acetate yields increased from 1.42% to 12.46% (p values < 0.0001) in three-weeks drying, reflecting the redox processes undergoing within the oil during drying. Several constituents (25) were found in one-week dried herbs' oil as compared to the fresh, two-, and three-weeks oils, which consisted of 23, 19, and 14 constituents, respectively, leading to the recommendation of the one-week drying of the herb for maximum oil yield. The DPPH (2, 2-diphenyl-1-picryl-hydrazyl) reactivity was highest for the two- and three-weeks dried herb-based oils, followed by the one-week dried- and fresh-herb-based oils (p < 0.0001), again indicating major chemical changes during herbs' dryings, affecting the free-radical scavenging capacity of these batches of oils obtained after different drying times.


Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans.
The ferrous iron and 2-oxoglutarate (2OG) dependent oxygenases catalyse two electron oxidation reactions by coupling the oxidation of substrate to the oxidative decarboxylation of 2OG, giving succinate and carbon dioxide coproducts. The evidence available on the level of incorporation of one atom from dioxygen into succinate is inconclusive. Here, we demonstrate that five members of the 2OG oxygenase family, AlkB from Escherichia coli, anthocyanidin synthase and flavonol synthase from Arabidopsis thaliana, and prolyl hydroxylase domain enzyme 2 and factor inhibiting hypoxia-inducible factor-1 from Homo sapiens all incorporate a single oxygen atom, almost exclusively derived from dioxygen, into the succinate co-product.


Semi-annual oscillations in Saturn's low-latitude stratospheric temperatures.
Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-microm methane and 12.2-microm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 +/- 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation.


Effect of protective agents, freezing temperature, rehydration media on viability of malolactic bacteria subjected to freeze-drying.
The effects of protective agents, rehydration media and freezing temperature on the viabilities of Lactobacillus brevis and Oenococcus oeni H-2 when subjected to freeze-drying were investigated. Several protectants and rehydration media were tested to improve the survival after freeze-drying. The cells were also frozen at -65 and -20 degrees C to check the effect of freezing temperature on the viability. The best protectant and rehydration medium to obtain the highest viability after freeze-drying varied with the species of bacteria. Yeast extract (4.0%) and sodium glutamate (2.5% ) gave maximum viability of L. brevis and O. oeni (67.8% and 53.6% respectively). The highest survival of L. brevis and O. oeni were obtained when rehydrated with 10% sucrose and MGY medium respectively. When the bacterial cells were frozen quickly (-65 degrees C) than slowly (-20 degrees C), L. brevis and O. oeni both showed increased viability after freeze-drying. The viabilities of L. brevis and O. oeni after freeze-drying were shown to be strain specific and dependent on protective agents, rehydration media and freezing temperature.


Effect of the test media and toxicity of LAS on the growth of Isochrysis galbana.
In this paper, the toxicity of linear alkylbenzene sulfonate (LAS) was evaluated in the marine microalga Isochrysis galbana using data of growth inhibition toxicity tests at 96-h exposure time. Toxicity was examined in standard conditions and by means of the modification of two variables of the test media: (1) the dilution water and (2) the content of nutrients in the test medium. For this purpose, a total of 10 toxicity test were designed: five dilution waters, four natural marine waters and one synthetic seawater; each in two different nutritive conditions, saturated nutrient concentration (SC) by the addition of modified f/2 nutritive medium, and natural nutrient concentration (NC), i.e., without the addition of f/2. At threshold toxicity levels, the dilution waters used in the test and the nutrient concentrations did not affect the toxicity of LAS. At IC50 concentrations, the toxicity of LAS is influenced by both variables: under SC conditions, the toxic effect of LAS diminishes, obtaining in all the tests IC50 > 10 mg/L LAS. Under NC conditions, IC50 concentrations ranging between 3.15 and 9.26 mg/L LAS have been obtained.


Programmed crystallization via epitaxial growth and ligand replacement towards hybridizing porous coordination polymer crystals.
Hybridized porous coordination polymers (PCPs) are synthesized through epitaxial growth or ligand replacement. Whereas epitaxial growth on the core crystal leads to a sandwich type PCP, ligand replacement near the surface of core crystal results in a core-shell type PCP.


An energy and leakage current monitoring system for abnormality detection in electrical appliances.
Unsafe electrical appliances can be hazardous to humans and can cause electrical fires if not monitored, analyzed, and controlled. The purpose of this study is to monitor the system's condition, including the electrical properties of the appliances, and to diagnose fault conditions without deploying sensors on individual appliances and analyzing individual sensor data. Using historical data and an acceptable range of normal and leakage currents, we proposed a hybrid model based on multiclass support vector machines (MSVM) integrated with a rule-based classifier (RBC) to determine the changes in leakage currents caused by installed devices at a certain moment. For this, we developed a sensor-based monitoring device with long-range communication to store real-time data in a cloud database. In the modeling process, RBC algorithm is used to diagnose the constructed device fault and overcurrent fault where MSVM is applied for detecting leakage current fault. To conduct an operational field test, the developed device was integrated into some houses. The results demonstrate the effectiveness of the proposed system in terms of electrical safety monitoring and detection. All the collected data were stored in a structured database that could be remotely accessed through the Internet.


Special Issue: New Advances in Bioinformatics and Biomedical Engineering Using Machine Learning Techniques, IWBBIO-2022.
Bioinformatics is revolutionizing Biomedicine in the way we treat and diagnose pathologies related to biological manifestations resulting from variations or mutations of our DNA [...].


CT features of lung metastases from pancreatic adenocarcinoma: Correlation with histopathologic findings.
The purpose of this study was to evaluate the prevalence of an atypical, alveolar presentation of pulmonary metastases from pancreatic adenocarcinoma (PDAC) on computed tomography (CT) and to correlate CT features with those obtained at histopathologic analysis. A total of 76 patients with lung metastases from PDAC over a 10-year period (2009-2019) in a French university hospital were retrospectively included. There were 34 men and 42 women with a mean age of 67.6±11.3 (SD) years (range: 38-89 years). CT features of PDAC were classified according to their presentations as usual metastatic pattern or atypical alveolar pattern; the atypical alveolar pattern corresponding to either ground glass nodules or opacities, solid nodules with a halo sign, "air-space" nodules with air bronchogram, or parenchymal consolidation. Imaging-histopathologic correlation was performed when tissue samples were available. Pulmonary metastases were synchronous in 36 patients (36/76; 47%) and metachronous in 40 patients (40/76; 53%). A predominant alveolar presentation on CT was observed in 17 patients (17/76, 22%). Nodules with halo sign were the predominant alveolar pattern in 7 patients (7/17; 41%), air-space nodules were predominant in 4 patients (4/17; 24%) whereas pure ground glass nodules and consolidations were observed as predominant features in 3 patients (3/17; 18%) each. For 5 patients who had histopathological confirmation, alveolar metastases of PDAC were characterized by columnar tumor cells lining the alveolar wall, which was not seen in other radiological presentations, whereas there were no differences regarding mucin secretion between pulmonary metastases with alveolar presentation and those with typical pattern. Lung metastases from PDAC may present with a so-called "alveolar" pattern on CT. This misleading CT features is found in 22% of patients with lung metastases from PDAC and is due to lepidic growth of the metastatic cells.


American tertiary clinic-referred bipolar II disorder compared to bipolar I disorder: More severe in multiple ways, but less severe in a few other ways.
Prevalence and relative severity of bipolar II disorder (BDII) vs. bipolar I disorder (BDI) are controversial. Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation. BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) disorders, first-degree relative with mood disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0±8.6 vs. 18.9±8.1 years), longer illness duration (19.0±13.0 vs. 16.1±13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1±1.4 vs. 3.7±1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%). American tertiary bipolar disorder clinic referral sample, cross-sectional design. Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII.


Overt GI bleeding from a Cameron lesion in an Ethiopian with NSAID use: Case report of an unusual condition.
Cameron Lesions are linear breaks in the proximal gastric mucosa, mostly in association with hiatal hernia. The condition presents with chronic iron deficiency anemia and occasionally with obscure bleeding. Overt bleeding is very rare and has not been reported in sub- Saharan Africa context. A 78 year old male patient, with an already diagnosed hiatal hernia and gouty arthritis, presented with massive upper GI bleeding requiring resuscitation and blood transfusion. The patient was taking indomethacin for a gout flare prior to the episode and clinical suspicion was a peptic ulcer disease as the culprit for the bleeding. Endoscopy was done and it showed two linear erosions with recent bleeding in the hernia sac. No other bleeding source was identified. The patient was treated with a Proton Pump Inhibitor (PPI). Cameron lesions could present with massive bleeding and should be actively looked for in patients with hiatal hernia as they could be easily missed. Even with concurrent NSAID use, the condition could be a cause of major bleeding and careful evaluation is important. Management entails PPI therapy with occasional endoscopic intervention. In the setting of hiatal hernia, Cameron lesions should be actively looked for in patients presenting with overt GI bleeding.


Cancer in interstitial pulmonary fibrosis and sarcoidosis.
The occurrence of lung cancer in patients with diffuse interstitial pulmonary disease is well-known. The incidence, however, varies and ranges from 9.8 to 38%. The pathogenesis of lung cancer in pulmonary fibrosis is unclear, but genetic as well as environmental factors seem to be involved.


Nuclear medicine in the assessment and prevention of cancer therapy-related cardiotoxicity: prospects and proposal of use by the European Association of Nuclear Medicine (EANM).
Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity.


Effects of steady-state plasma vasopressin levels on the distribution of intrarenal blood flow on electrolyte excretion.
1. In order to evaluate the effects of arginine vasopressin (AVP) on the distribution of intrarenal blood flow and on electrolyte excretion, steady-state plasma AVP levels (4-8, 19-1, 44-3, and 100-6 micro u./ml.) were produced in anaesthetized dogs, which were hydrated to minimize endogenous anti-diuretic hormone (ADH) release. 2. The urinary excretion of sodium and potassium increased without change in their filtered loads during AVP infusion. 3. Measurement by the 133xenon washout method revealed diphasic blood flow shifts, as a function of the plasma AVP level, between compartment 1 (outer cortex) and compartment 2 (inner cortex and outer medulla) without change in compartment 3 (inner medulla). 4. In a separate study, the radioactive microsphere (15 micronm) method was used with a plasma AVP levels of 19-8 micronu./ml. Blood flow (expressed as % flow/g tissue) decreased in the outer cortex and increased in the inner cortex. 5. Total renal blood flow did not change during infusion of AVP. However, the values measured by 133xenon were lower than those measured by the microsphere method. 6. There was agreement between these two independent methods that blood flow shifted from outer to inner cortex, with no change in total renal flow, at similar plasma AVP levels (19-1 and 19-8 micronu./ml.). The relationship of these intrarenal circulatory changes to the increased electrolyte excretion is discussed.


Identification of intrinsic termination sites in vitro for RNA polymerase II within eukaryotic gene sequences.
We have identified and mapped several DNA sequences within a human histone gene (H3.3) at which in-vitro transcription by highly purified RNA polymerase II is efficiently terminated. Since transcription in our system involves only RNA polymerase II acting on a linear DNA template, these sequences contain "intrinsic" termination signals recognized by the polymerase protein itself. The existence of such signals within a gene suggests that efficient antitermination systems probably exist for mammalian transcription units. Alternatively, there could be a high frequency of premature transcription termination, or "polarity" for genes such as H3.3. Intrinsic transcription termination sites in H3.3 are located in sequences of consecutive thymidylate residues (5 to 8 nucleotides) on the non-transcribed DNA strand (T-runs), from which it is likely that such T-runs are elements of the intrinsic termination signal for RNA polymerase II. However, transcription proceeds without significant termination through many similar T-runs, from which it follows that these intrinsic termination signals include other elements. Since transcription is also terminated efficiently at these sites when the transcript remains bound along its full length as a DNA-RNA hybrid, it is unlikely that formation of specific RNA secondary structures in the transcript is a general element of the intrinsic termination signal. Although DNA sequences downstream from the coding portion of the mouse beta-globin gene have been implicated as sites of transcription termination in vivo, these regions do not contain strong intrinsic termination signals, and transcription in vitro proceeds through these regions almost undiminished. Transcriptional termination in this region in vivo may depend on the presence of termination factors or other intracellular elements, and there may be multiple classes of DNA signals that control eukaryotic termination.


Epitopes on Cry j I and Cry j II for the human IgE antibodies cross-reactive between Cupressus sempervirens and Cryptomeria japonica pollen.
Forty sea from French patients allergic to Cupressus sempervirens pollen were tested for cross-reactivities against Cry j I, Cry j II (major allergens of Cryptomeria japonica pollen) and other pollen allergens from botanically related plants. Seventy-three per cent of the sera reacted with either Cry j I or Cry j II, or with both of them. These IgE cross-reactions were blocked effectively by mAb 046 (anti-Cry j I) or N26, T27 (anti-Cry j II), and weakly by mAbs 052, 027 and 026 (anti-Cry j I). Furthermore, the IgE antibodies in two sera, #40 and #11, bound to peptide fractions obtained from enzyme-digested Cry j I, and mAb 027 could also bind to the fractions. Analyses of the amino acid sequences of the peptides revealed that reactive peptides contained "NGNATPQLTKNAGVLTCSLSKR" sequence and the third residue N3 was glycosylated, however, when the N3 was not glycosylated, the IgE antibodies did not react, but mAb 027 could. The glycosylation of the N3 might be required for IgE-binding to the peptides. Sugar component on the N3 residue was found to be 0.4 mol galactose, 1.3 mol mannose, 0.8 mol fucose and 2.0 mol N-acetyl-glucosamine. Cross-reactivities against other pollen allergens from botanically related plants were found in most of the sera. However, many of these reactivities were detected by sandwich ELISA but not by an ELISA using allergen-coated plates, indicating that it is important to select an appropriate ELISA procedure in order to detect an allergen or an IgE antibody to an allergen.


Are any functionally mature cells of medullary phenotype located in the thymus cortex?
Experiments were undertaken to test if thymocytes of "mature" or "medullary" phenotype were restricted to the medullary area of the thymus. A calculation based on direct cell counts on serial sections indicated that 11.5% of adult male CBA thymic lymphoid cells were within the medullary zone. Since only 3-4% of thymocytes were cortisone resistant, the majority of thymocytes within the medulla were, like cortical thymocytes, cortisone sensitive. A series of cell surface antigenic markers, used alone or in pairs, suggested that 13-15% of thymocytes were of medullary phenotype, somewhat more than the number of thymocytes actually present in the medulla. However, much of this discrepancy could be explained by differential death of cortical cells during isolation and staining, and by the existence in the cortex of a subpopulation of early blast cells which shared some, but not all markers with medullary thymocytes. A direct test for mature or medullary phenotype cells in the cortex involved selective transcapsular labeling of outer-cortical cells with fluorescent dyes, followed by multiparameter immunofluorescent analysis of the 10% labeled population. Outer-cortical thymocytes included some cells (mainly early blasts) sharing some markers with medullary thymocytes, but very few (less than 1%) of these cells expressed all the characteristic "mature" markers. Limit-dilution precursor frequency studies showed the level of functional cells in the outer cortex was extremely low. The overall conclusion was that the vast majority of cells of complete "mature" phenotype are confined to the thymic medulla. These findings favor the view that thymus migrants originate from the thymic medulla, but do not exclude a cortical origin. The results also illustrate the need for multiparameter analysis to distinguish medullary thymocytes from early blast cells.


Cost-utility of a psychoeducational intervention in fibromyalgia patients compared with usual care: an economic evaluation alongside a 12-month randomized controlled trial.
To determine the effectiveness of adding psychoeducational treatment implemented in general practice to usual care for patients with fibromyalgia (FM), and to analyze the cost-utility of the intervention from health care and societal perspectives. Twelve-month randomized controlled trial. A total of 216 primary care patients meeting the American College of Rheumatology criteria for FM participated in the study. The intervention included 9, 2-hour sessions of psychoeducation (5 sessions of education about the illness+4 sessions of autogenic relaxation) added to usual care provided by a multidisciplinary group in general practice was compared to usual care in the public health system. At 12-month follow-up, patients who received psychoeducation showed greater improvement in global functional status (Cohen d=0.36; -2.49 to 3.81), physical functioning (Cohen d=0.56; 0.08 to 1.00), days feeling well (Cohen d=0.40; -0.16 to 1.02), pain (Cohen d= 0.35; -0.04 to 0.80), morning fatigue (Cohen d=0.24; -0.20 to 0.76), stiffness (Cohen d=0.34; -0.10 to 0.87), and depression (Cohen d=0.30; -0.26 to 0.93). Mean incremental cost per person receiving the intervention was &OV0556;-215.49 (-615.13 to 287.81) from the health care perspective, and &OV0556;-197.32 (-785.12 to 395.74) from the societal perspective. The incremental gain in quality-adjusted life-years per person was 0.12 (0.06 to 0.19), yielding a "dominant" intervention from both perspectives. The sensitivity analysis suggested that the intervention was cost-effective even imputing all missing data. Our findings demonstrate the long-term clinical effectiveness of a psychoeducational treatment program for FM implemented at primary care level and the cost-utility from a health care and societal perspective. NCT00550966.


Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet.
The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma beta-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.


Stability control for breath analysis using GC-MS.
Gas chromatography mass spectrometry (GC-MS) instruments provide researchers and clinicians with a vast amount of information on sample composition, thus these instruments are seen as gold standard in breath analysis research. However, there are many factors that can confound the data measured by GC-MS instruments. These factors will make interpretation of GC-MS data unreliable for breath analysis research. We present in this paper detailed studies of two of these factors: instrument variation over time and chemical degradation of known biomarkers during storage in sorbent tubes. We found that a single quadrupole MS showed larger variability in measurements than a quadrupole time-of-flight MS when the same mixture of chemical standards was analysed for a period of up to 8 weeks. We recommend procedures of normalising the data. Moreover, the stability studies of breath biomarkers like thioethers, previously found indicative of malaria, showed that there is a need to store the samples in sorbent tubes at low temperature, 6 °C, for no more than 20 days to avoid the total decay of the chemicals.


Sex differences in patterns of associative memory-related activation in individuals at risk of Alzheimer's disease.
The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how relationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in understanding the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.


Acoustic overstimulation activates 5'-AMP-activated protein kinase through a temporary decrease in ATP level in the cochlear spiral ligament prior to permanent hearing loss in mice.
Inner ear disorders are known to be elicited by mitochondrial dysfunction, which decreases the ATP level in the inner ear. 5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase activated by metabolic stress and by an increase in the AMP/ATP ratio. To elucidate the involvement of AMPK-derived signals in noise-induced hearing loss, we investigated whether in vivo acoustic overstimulation would activate AMPK in the cochlea of mice. Std-ddY mice were exposed to 8kHz octave band noise at a 90-, 110- or 120-dB sound pressure level (SPL) for 2h. Exposure to the noise at 110 or 120dB SPL produced outer hair cell death in the organ of Corti and permanent hearing loss. Exposure to the noise at 120-dB SPL elevated the level of the phospho-AMPK α-subunit (p-AMPKα), without affecting the protein level of this subunit, immediately and at 12-h post-exposure in the lateral wall structures including the spiral ligament and stria vascularis. In the hair cells and spiral ganglion cells, no marked change in the level of p-AMPKα was observed at any time post-exposure. The level of phospho-c-Jun N-terminal kinase (p-JNK) was increased in the lateral wall structures at 2- to 4-h post-exposure at 120dB SPL. Noise exposure significantly, but temporarily, decreased the ATP level in the spiral ligament, in an SPL-dependent manner at 110dB and above. Likewise, elevation of p-AMPKα and p-JNK levels was also observed in the lateral wall structures post-exposure to noise at an SPL of 110dB and above. Taken together, our data suggest that AMPK and JNK were activated by ATP depletion in the cochlear spiral ligament prior to permanent hearing loss induced by in vivo acoustic overstimulation.


Influence of irbesartan on expression of ILK and its relationship with epithelial-mesenchymal transition in mice with unilateral ureteral obstruction.
Irbesartan, a new antagonist of the type 1 angiotensin II receptor, has been proven to be renal protective in both diabetic and non-diabetic nephropathy, but its exact mechanism is still uncertain. Here we investigated the influence of irbesartan on the expression of the integrin-linked kinase (ILK) and its relationship with epithelial-mesenchymal transition (EMT) in mice with unilateral ureteral obstruction (UUO). The mice were randomly divided into 3 groups: sham operation (C, n=20), UUO (n=40), and UUO with irbesartan treatment (UUO+irbesartan, n=40). Irbesartan was given at a dose of 50 mg/kg body weight per day by gavage. The experimental animals in the control group received the same volume of vehicle (0.9% saline solution). The animals were sacrificed at d 1, 3, 7, and 14, respectively, after the surgery. The expression of the ILK at mRNA and protein levels were significantly increased in the UUO group 1 d after the surgery, which was significantly decreased by treatment with irbesartan (P<0.01, respectively). The expression of alpha-smooth muscle actin (alpha-SMA) was significantly increased, while E-cadherin was decreased in mice with UUO at d 3 after the surgery. Treatment with irbesartan significantly abrogated such effects (P<0.01). The immunohistochemistry analysis indicated that the protein expression of the ILK was positively correlated with alpha-SMA, but negatively with E-cadherin. These results suggested that irbesartan attenuated renal tubulointerstitial fibrosis in UUO mice, which may be related to the inhibition of ILK expression, subsequently preventing the tubular EMT.


Comprehensive and Collaborative Pharmacist Transitions of Care Service for Underserved Patients with Chronic Obstructive Pulmonary Disease.
Mortality risk from chronic obstructive pulmonary disease (COPD) increases significantly in the first year after a 30-day hospital readmission. To evaluate a comprehensive and collaborative pharmacist transitions of care service for patients hospitalized with COPD compared to usual care. In this within-site, retrospective study, discharge counseling, medication reconciliation, medication access assistance, therapy changes, and post-discharge long-term follow-up were provided to underserved adult patients with a primary care provider at the study clinic and admitted to the affiliated hospital with a primary diagnosis of COPD exacerbation. Primary outcome was a 180-day composite of COPD-related hospitalizations and emergency department (ED) visits. Secondary outcomes were 30-, 60-, 90-, and 180-day events, costs, pharmacist interventions, time to follow-up, and pneumonia. Sixty-five patients were identified with a total of 101 index admissions. The mean age was 62.5 years, approximately 55.3% were female, and 67.7% were black or African American. The primary composite was significantly lower in the pharmacist intervention group compared to usual care (mean difference 0.82, P=0.0364, 95% confidence interval [CI] 0.05-1.60), driven by lower 30-day hospitalizations in the intervention group (mean difference 0.15, P=0.0099, 95% CI 0.04-0.27). Cost associated with COPD-related hospitalizations was significantly lower in the pharmacist intervention group compared to usual care ($173,808, P = 0.0330) as well as before intervention ($79,662, P=0.0233). There was no significant difference in time to follow-up or pneumonia. A comprehensive, collaborative pharmacist transitions of care service significantly reduced 30-day COPD-related hospital readmissions, ED re-visits, and associated costs in an underserved population.


Data Analysis WorkbeNch (DAWN).
Synchrotron light source facilities worldwide generate terabytes of data in numerous incompatible data formats from a wide range of experiment types. The Data Analysis WorkbeNch (DAWN) was developed to address the challenge of providing a single visualization and analysis platform for data from any synchrotron experiment (including single-crystal and powder diffraction, tomography and spectroscopy), whilst also being sufficiently extensible for new specific use case analysis environments to be incorporated (e.g. ARPES, PEEM). In this work, the history and current state of DAWN are presented, with two case studies to demonstrate specific functionality. The first is an example of a data processing and reduction problem using the generic tools, whilst the second shows how these tools can be targeted to a specific scientific area.


A partially crosslinked bicontinuous cubic phase exhibiting a temperature range of more than 100 °C.
A new methodology of partial crosslinking is presented for stabilizing the bicontinuous cubic phase without losing its dynamic nature. It was applied to a mixture of 1,2-bis[4'-(9''-decenyloxy)benzoyl]hydrazine with a bi-functional linker, remarkably stabilizing the phase in comparison with the neat compound having no C=C bond at the end of the alkyl tail.


Correction to: The search for, and chemistry and mechanism of, neurotrophic natural products.
he article The search for, and chemis.


The stability of the auditory evoked potentials in normal man and patients with multiple sclerosis.
Sequential records of the early and middle components of the auditory evoked potential in response to a click stimulus have been obtained over a period of 2.5 years in normal subjects and in patients with multiple sclerosis. The latencies of all the components were highly consistent in the control subjects and in the patients who were clinically stable throughout the period of study. In constrast, in some of the patients who had clinical relapses during the study there was variation in the latency and amplitude of some of the components. The significance of this variation is discussed and the poor correlation between the sites of the new lesions as determined clinically and the auditory evoked potential variability is emphasised.


Synthetic peptides bioinspired in temporin-PTa with antibacterial and antibiofilm activity.
Several antimicrobial peptides (AMPs) have been reported in amphibian toxins, as temporin-PTa from Hylarana picturata. The amino acid distribution within a helical structure of AMPs favors the design of new bioactive peptides. Therefore, this work reports the rational design of two new synthetic peptides denominated Hp-MAP1 and Hp-MAP2 derived from temporin-PTa. These peptides present an amphipathic helix with positive charges of +4 and +5, hydrophobic moment (<µH>) of 0.66 and 0.72 and hydrophobicity (<H>) of 0.49 and 0.41, respectively. Hp-MAP1 and Hp-MAP2 displayed in vitro activity against Gram-negative and Gram-positive bacteria from 2.8 to 92 µM, without presenting hemolytic effects. Molecular dynamics simulation suggested that the parent and designed temporin-like peptides lack structural stability in an aqueous solution. By contrast, α-helical structures were predicted in hydrophobic and anionic environments. Additionally, the peptides were simulated on mimetic membranes composed of anionic and neutral phospholipids 1,2-dipalmitoylsn-glycerol-3-phosphatidylglycerol (DPPG-anionic), 1,2-dipalmitoyl-sn-lyco-3 phosphatidylethanolamine (DPPE-neutral). When in contact with DPPG/DPPE (90:10) and DPPG/DPPE (50:50) temporin-PTa, Hp-MAP1 and Hp-MAP2 established interactions guided by hydrogen and saline bounds. Therefore, the findings described here reveal that the optimization of the amphipathic α-helical cationic peptides Hp-MAP1 and Hp-MAP2 enabled the generation of new synthetic antimicrobial agents to combat pathogenic microorganisms.


Selective image-guided venous sinus exposure for direct embolization of dural arteriovenous fistula: technical case report.
Transcranial approaches for transsinusal endovascular therapy of DAVF have been sporadically reported by large craniectomies. Large craniectomies carry nevertheless a risk of postembolization extradural hematoma, reduced by delaying the endovascular procedure. We report a 1-session technique of SIGC for percutaneous transvenous DAVF embolization. This 58-year-old woman developed a right-sided cerebellar hematoma in relation with a high-grade left transverse and sigmoid sinus DAVF. The DAVF was fed by branches from the left vertebral artery, left internal, and left external carotid arteries, draining into the transverse sinus with retrograde flow in cortical veins. Transvenous retrograde embolization was not feasible either through the left internal jugular vein because of thrombosis, or through the right one because of torcular septa. During the same anaesthetic session, a 5-cm-length selective craniectomy was shaped under magnetic resonance image guidance navigation according to the left transverse sinus with high-speed drill. Thereafter, back in the angiography room, the transverse sinus was taped and coiled resulting in a complete exclusion of the DAVF. Selective image-guided craniectomy is efficient and safe for direct percutaneous transvenous embolization of DAVF in a single anesthetic session. Leaving bone beside the sinus prevents a parenchymal traumatic puncture. This bone has nevertheless to be drilled to allow an adequate sharp puncture angle. Doing so, postoperative hematoma is prevented by the small bone opening, the natural adherence of the dura matter and the possibility of direct compression.


What Health Service Provider Factors Are Associated with Low Delivery of HIV Testing to Children with Acute Malnutrition in Dowa District of Malawi?
The Community-based Management of Acute Malnutrition is the national program for treating acute malnutrition in Malawi. Under this program's guidelines all children enrolled should undergo an HIV test, so that those infected can receive appropriate treatment and care. However, the national data of 2012 shows a low delivery of testing. Prior studies have investigated client-related factors affecting uptake of HIV testing in Community-based Management of Acute Malnutrition program. Lacking is the information on the service provider factors that are associated with the delivery of testing. This study investigated service provider factors that affect delivery of HIV testing among children enrolled in the program and explored ways in which this could be improved. A descriptive study that used qualitative methods of data collection. Client registers were reviewed to obtain the number of children enrolled in Community-based Management of Acute Malnutrition and the number of children who were tested for HIV over a 12-month period. In-depth interviews were conducted with Community-based Management of Acute Malnutrition and HIV Testing and Counselling focal persons to investigate factors affecting HIV test delivery. Descriptive statistics were used to analyze data from client registers. Information from interviews was analyzed using a thematic approach. Quantitative data revealed that 1738 (58%) of 2981 children enrolled in Community-based Management of Acute Malnutrition were tested for HIV. From in-depth interviews four themes emerged, that is, lack of resources for HIV tests; shortage of staff skilled in HIV testing and counseling; lack of commitment among staff in referring children for HIV testing; and inadequately trained staff. There is a need for a functioning health system to help reduce child mortality resulting from HIV related conditions.


Ethyl 2-(4-nitro-phen-yl)-1-[3-(2-oxopyrrolidin-1-yl)prop-yl]-1H-benzimidazole-5-carboxyl-ate.
In the title compound, C(23)H(24)N(4)O(5), the essentially planar benzimidazole ring system [maximum deviation = 0.008 (2) Å] forms a dihedral angle of 39.22 (7)° with the attached nitro-benzene ring. The pyrrolidin-2-one ring adopts an envelope conformation with a C atom as the flap. In the crystal, mol-ecules are connected by C-H⋯O inter-actions, forming sheets propagating in (011). The crystal packing also features weak π-π stacking inter-actions [centroid-centroid = 3.6746 (12) Å].


Increasing number and shifting demographics of adolescent opioid use disorder presentations to the emergency department.
Opioid use has been increasing in adolescents; however, lacking are data describing sex, ethnicity, and age groups most affected. We identified and characterized the trend in the adolescent population who presented to the emergency departments (ED) of a large hospital system. We obtained data directly from the electronic medical record for patients aged 12-21 years from January 2014 to December 2022. We identified opioid-related visits by primary diagnosis. Trends were compared amongst age groups and by sex and reported ethnicity. Opioid-related presentations increased in all age groups and were significantly increased in adolescents aged 13-17 years compared to patients aged 18-21 years (1700% [range: 1000-3300%] v 400% [200-800%]; p = 0.02). Adolescents presenting to the ED with opioid-related primary diagnoses were more likely to be Hispanic and male in our region. Over the last two years (2021-22) there was a significant increase in opioid-related presentations to our hospital system amongst adolescents and an acceleration post-COVID. In 2022, emergency department presentations shifted to younger teenagers and from white young adults to Hispanic adolescents. The increased number of cases posed management problems in the ED given the lack of outpatient treatment options. Opioid-related ED presentations are increasing in adolescents with post-COVID increases in male, Hispanic, and younger patients in our region. Pathways for outpatient treatment need to be developed for adolescents with OUD.


Isolation and characterization of a strictly anaerobic, cellulolytic spore former: Clostridium chartatabidum sp. nov.
Cellulolytic, strictly anaerobic spore-forming bacteria were isolated from chloroform treated rumen contents. They were different from previously described cellulolytic rumen clostridia in several characteristics. They formed subterminal rod-shaped spores approximately 0.7 micron by 3.5 micron. In broth cultures the growth rate was maximal at 39 degrees C and after log growth extensive autolysis occurred. Fermentation products consisted of acetate, butyrate, hydrogen and ethanol. The GC content was 31%.


Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study.
Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment. Primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptom score. Adverse events and vital signs were assessed. CAARS-Inv:SV Total ADHD Symptom scores decreased 30.2% (p < .001) during treatment. Similar, significant decreases were noted for the secondary efficacy measures, including the Sheehan Disability Scale Total score, which improved 25.3% (p < .001). Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects. Results of this open-label study support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD.


A review on the biological roles of LncRNA PTCSC3 in cancerous and non-cancerous disorders.
Long non-coding RNA papillary thyroid carcinoma susceptibility candidate 3 (LncRNA PTCSC3) is located on human chromosome 14q13.3. PTCSC3 functions as a tumor suppressor lncRNA to regulate essential cellular processes such as apoptosis, cell proliferation, migration, invasion, angiogenesis, and epithelial-to-mesenchymal transition. PTCSC3 is also involved in the regulation of the Wnt/β-catenin signaling pathway, aerobic glycolysis, and p53 pathways. Downregulation of PTCSC3 has been associated with an increased risk of many tumors such as thyroid, gastric, laryngeal, breast, cervical, oral, lung, and glioma cancers. In addition, dysregulation of PTCSC3 has been reported in non-cancerous disorders notably osteoporosis and periodontitis. However, a number of single nucleotide polymorphisms at PTCSC3 have been linked to a higher risk of human diseases. This literature review summarizes the diagnostic, prognostic, and the clinical value of abnormal expression of PTCSC3 in cancerous and non-cancerous disorders and comprehensively analyzes potential molecular regulatory mechanism related to PTCSC3, which is expected to provide clear guidance for future PTCSC3 research.


Effect of physostigmine on relative acetylcholine output induced by systemic treatment with scopolamine in in vivo microdialysis of rat frontal cortex.
By means of an in vivo brain microdialysis, the effect of different concentrations of physostigmine on the acetylcholine level in the dialysate of rat frontal cortex was studied. Perfusion of the various degrees of physostigmine (eserine) concentration (10 nM-10 microM) into the cortex through the dialysis membrane increased the basal acetylcholine level in a dose-dependent manner. In the presence of 10 nM, 0.1 microM and 10 microM physostigmine in the perfusate, systemic treatment with scopolamine (0.5 mg/kg, i.p.) increased 200, 270 and 510%, respectively, the relative acetylcholine level in the dialysates in comparison with the corresponding basal levels, while in the absence of physostigmine the treatment increased it only 40%. From these results, it appears that perfusion of physostigmine at a variety of concentrations, changes not only the basal level of acetylcholine induced by the inhibition of acetylcholinesterase but also the relative acetylcholine output induced by systemic treatment with scopolamine.


Urinary concentrations and bactericidal activity against amoxicillin-nonsusceptible strains of Escherichia coli with single-dose, oral, sustained-release amoxicillin/clavulanic acid: a phase I, open-label, noncomparative clinical trial in healthy volunteers.
Urinary tract infections (UTIs) account for 5 to 6 million medical consultations in the United States each year. Worldwide, an estimated 20% to 30% of women aged 20 to 40 years have at least 1 episode of the most common type of UTI (uncomplicated cystitis) in their lifetime, with Escherichia coli being the causative pathogen in 80% of cases. Antibacterial activity in urine has been shown to be correlated with outcomes of uncomplicated cystitis. The objectives of this study were to determine urinary concentrations and ex vivo bactericidal activity of sustained-release (SR) amoxicillin/clavulanic acid 2000/125 mg against intermediately resistant and resistant strains of E coli over 72 hours and compare them with those of a susceptible strain. This study also investigated whether urinary concentrations obtained after dosing cover E coli strains categorized as intermediately resistant and resistant based on current Clinical and Laboratory Standards Institute (formerly NCCLS) breakpoints in uncomplicated cystitis. This Phase I, open-label, noncomparative study in healthy male volunteers was conducted at the Pharmacology Unit, Autónoma University, Madrid, Spain. Subjects received a single oral dose of amoxicillin/clavulanic acid 2000/125 mg SR. The amoxicillin/clavulanic acid MICs were 8/4 microg/mL (susceptible), 16/8 microg/mL (intermediately resistant), and 32/16 and 64/32 microg/mL (resistant). Urine samples were collected before (baseline; time 0) and at the following intervals: 0-2, 2-4, 4-8, 8-12, 12-16, 16-24, 24-36, 36-48, 48-60, and 60-72 hours after dosing. Killing curves with urine samples were performed with initial inocula of approximately 10(7) colony-forming units (CFU)/mL, and bactericidal activity (defined as >3 log(10) CFU/mL and >99.9% reduction in bacterial counts) was calculated as the difference between log(10) initial inoculum and log(10) CFU/mL after 4 hours of incubation of each sample. Twelve volunteers were included (mean [SD] age, 24.83 [5.64] years; mean [SD] height, 175.75 [7.56] cm; and mean [SD] weight, 73.55 [9.19] kg). No statistically significant differences between the activities in the 12-16-hour interval compared with baseline were found in any of the strains tested. Bactericidal activity against the susceptible and intermediately resistant strains (MICs 8/4 and 16/8 g/mL, respectively) was obtained up to 8 hours after dosing. Bactericidal activity against the resistant strains (MICs 32/16 and 64/32 microg/mL) was obtained in the 2-4-hour interval. In this Phase I study in healthy volunteers, urinary concentrations after dosing with amoxicillin/clavulanic acid 2000/125 mg SR showed bactericidal activity against the amoxicillin-susceptible and intermediately resistant strains of E coli.


Prelude to a successful site visit, part 2.
This column provides information on accreditation for nursing programs of all types. Readers may submit questions to the Accreditation Commission for Education in Nursing. General questions of interest to a wide audience will be addressed in this column, whereas more specific questions or those requiring confidentiality will be answered directly.


Field evidence for surface-wave-induced instability of sand dunes.
Field studies of barchans--crescent-shaped dunes that propagate over solid ground under conditions of unidirectional wind--have long focused on the investigation of an equilibrium between sand transport by wind and the control of air flow by dune topography, which are thought to control dune morphology and kinematics. Because of the long timescale involved, however, the underlying dynamic processes responsible for the evolution of dune fields remain poorly understood. Here we combine data from a three-year field study in the Moroccan Sahara with a model study to show that barchans are fundamentally unstable and do not necessarily behave like stable solitary waves, as suggested previously. We find that dune collisions and changes in wind direction destabilize the dunes and generate surface waves on the barchans. Because the resulting surface waves propagate at a higher speed than the dunes themselves, they can produce a series of new barchans of elementary size by breaking the horns of large dunes. The creation of these new dunes provides a mechanism for sand loss that prevents dune fields from merging into a single giant dune and therefore plays a fundamental role in the control of size selection and the development of dune patterns.


The saturated response of vertebrate rods and its relation to cGMP metabolism.
Strong light flashes saturate the response of a rod, and increasing flash intensities prolong the period of saturation. We have found that the period of saturation lengthens from base to tip of the outer segment and we have shown that free cGMP is replenished locally to terminate saturation and not in the G-cyclase rich axonemal region near the inner segment which contains the cell mitochondria. Our results also show that each section of outer segment acts as an independent module in this phase of transduction.


Demographic disparities in numeracy among emergency department patients: evidence from two multicenter studies.
To estimate the prevalence and demographic disparities in limited numeracy among emergency department (ED) patients. We performed two cross-sectional studies of ED patients with sub-critical illness in 2000-2001 and 2006. We enrolled 959 adult patients from 28 EDs in 17 US states and measured numeracy based on four validated questions. Rates of correct responses for individual numeracy questions ranged from 15% to 68%; only 11% of participants answered all questions correctly. Several demographic characteristics were independently associated with frequency of correct answers, including age (OR 0.92 [95% confidence interval (CI), 0.87-0.97] per (upward arrow) 5 years), race/ethnicity (compared to whites: OR 0.35 for blacks [95%CI, 0.20-0.63]; and OR 0.36 for Hispanics [95%CI, 0.19-0.69]), education (OR 4.74 [95%CI, 2.01-11.14] for high school graduates vs. not), health insurance (OR 1.70 [95%CI, 1.06-2.71] for those with private insurance vs. not), and income (OR 1.13 [95%CI, 1.05-1.22] per (upward arrow) $10,000). We found a higher prevalence of limited numeracy among ED patients compared to the general population. Significant demographic disparities are consistent with previous observations for general health literacy. Greater understanding of the high prevalence of limited numeracy may guide healthcare providers to simplify messages and communicate health information more effectively.


Effects of washing step and salt-addition levels on textural and quality properties in the chicken-surimi products.
The massive wastewater from surimi manufacture and salt addition is controversial. In our previous study, a chicken-surimi (CS) product can be successfully developed from the spent-hen breast via 3 times of washing steps and 2.5% salt addition in the recipe. Due to the characteristics of broiler breast (higher protein contents in muscle), this study was to optimize the washing step for CS batter recovered from broiler breast and the salt-addition level in the CS-product recipe. The step of washing once with 0.1% salt solution showed no (P > 0.05) differences in the texture profile and color parameters (expect a* value) in CS batters compared to initial washing steps (a 3-step washing procedure). The CS batter obtained by this washing step had higher amino-acid contents than boiler breast and large Grade A egg and even fit adults' daily essential amino-acid requirement. Besides, the lower (P < 0.05) water loss of cooked CS products during the storage (4°C) was shown beyond 2.0% salt addition in CS products. For efficient/ecofriendly extraction and sodium-content reduction, the washing once with a 0.1% salt solution and 2% salt addition in the recipe is recommended in the CS batter recovered from broiler breast and its products, respectively.


Vinpocetine mitigates DMH-induce pre-neoplastic colon damage in rats through inhibition of pro-inflammatory cytokines.
Colorectal cancer (CRC) is currently recognized as the third most prevalent cancer worldwide. Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine. It has been found effective in ameliorating the growth and progression of cancerous cells. However, its pharmacological effect on colon damage remains elusive. Hence, in this study, we have shown the role of vinpocetine in DMH-induced colon carcinogenesis. At first, male albino Wistar rats were administered with DMH consistently for four weeks to induce pre-neoplastic colon damage. Afterward, animals were treated with vinpocetine (4.2 and 8.4 mg/kg/day p.o.) for 15 days. Serum samples were collected to assess the physiological parameters, including ELISA and NMR metabolomics. Colon from all the groups was collected and processed separately for histopathology and western blot analysis. Vinpocetine attenuated the altered plasma parameters; lipid profile and showed anti-proliferative action as evidenced by suppressed COX-2 stimulation and decreased levels of IL-1β, IL-2, IL-6, and IL-10. Vinpocetine is significantly effective in preventing CRC which may be associated with its anti-inflammatory and antioxidant potential. Accordingly, vinpocetine could serve as a potential anticancer agent for CRC treatment and thus be considered for future clinical and therapeutic research.


Splenorenal bypass for right renal artery revascularization.
Splenic artery to right renal artery bypass was used successfully for surgical correction of renovascular hypertension in an elderly patient. The technique used is described.


Acceptance and commitment therapy: empirical considerations.
Cognitive-behavioral therapy (CBT), including behavior therapy, cognitive therapy, and their integration, has evolved over the past four decades to become the most empirically supported psychological treatment for a range of psychiatric conditions, spanning the preponderance of Axis I disorders, selected Axis II disorders, and a range of associated clinical-health problems. The evolution of cognitive-behavioral theory and treatment has followed a coherent scientific framework, first introduced in the cognitive-behavioral modeling and treatment of depression, to include: (a) systematic clinical observations, (b) definition and psychometric operationalization of key disorder-specific cognitive, emotional and behavioral constructs, (c) laboratory investigation of operationalized disorder-specific processes, (d) development of comprehensive CBT treatment interventions to target the processes of empirically tested disorder-specific models, (e) progression from early noncontrolled clinical outcome studies to the development of sophisticated, large-scale randomized controlled trials testing disorder-specific CBT interventions, (f) examination of disorder-specific moderators and mediators of change in CBT treatment, and (g) openness to refinements and elaborations based on empirical updates from experimental and clinical investigations.


Spikes with and without concurrent high-frequency oscillations: Topographic relationship and neural correlates using EEG-fMRI.
Epilepsy surgery is the best therapeutic option for patients with drug-resistant focal epilepsy. During presurgical investigation, interictal spikes can provide important information on eligibility, lateralisation and localisation of the surgical target. However, their relationship to epileptogenic tissue is variable. Interictal spikes with concurrent high-frequency oscillations (HFOs) have been postulated to reflect epileptogenic tissue more reliably. Here, we studied the voltage distribution of scalp-recorded spikes with and without concurrent HFO and identified their respective haemodynamic correlates using simultaneous electroencephalography and functional Magnetic Resonance Imaging (EEG-fMRI). The scalp topography of spikes with and without concurrent HFOs were assessed in 31 consecutive patients with focal drug-resistant epilepsy who showed interictal spikes during presurgical evaluation. Simultaneous EEG-fMRI was then used in 17 patients with spikes and concurrent HFOs. Haemodynamic changes were obtained from the spatial correlation between the patient-specific voltage map of each spike population and the intra-scanner EEG. The haemodynamic response of spikes with and without HFOs were compared in terms of their spatial similarity, strength, the distance between activation peaks and concordance with interictal localisation. Twenty-five patients showed spikes with and without concurrent HFOs. Among patients with both types of spikes, most spikes were not associated with HFOs (p < 0.0001, Mann-Whitney test). Twenty of the 25 patients showed an average of 8 ± 6 (standard deviation) electrodes with significant voltage differences (p = 0.025, permutation test corrected for multiple comparisons) on scalp electrodes within and distant to the spike field. Comparing the haemodynamic response between both spike populations, we found no significant differences in the peak strength (p = 0.71, Mann-Whitney test), spatial distribution (p = 0.113, One-sample Wilcoxon test) and distance between activation peaks (p = 0.5, One-sample Wilcoxon test), with all peaks being co-localised in the same lobe. Our data showed that spikes with and without HFOs have different scalp voltage distributions. However, when assessing the haemodynamic changes of each spike type, we found that both elicit similar haemodynamic changes and share high spatial similarity suggesting that the epileptic networks of spikes with and without HFOs have the same underlying neural substrate.


A new method for sex estimation based on femoral cross-sectional geometry measurements and its validation using recent and ancient populations.
Estimating sex is a fundamental task in biological and forensic anthropology. This study aimed to develop new methods for sex estimation based on femoral cross-sectional geometry (CSG) variables and to test their applicability in recent and ancient assemblages. The sample was divided into a study group (living individuals, N = 124) for creating sex prediction equations and two test groups: living individuals (N = 31) and prehistoric individuals (N = 34). The prehistoric sample was divided into three subgroups according to subsistence strategy (hunter-gatherers, early farmers that also hunted, and farmers and herders). Femoral CSG variables (size, strength, and shape) were measured from CT images using dedicated software. Discriminant functions for sex estimation were calculated for various bone completeness scenarios and validated using the test groups. Size and strength parameters were sexually dimorphic, while shape was not. Discriminant functions for sex estimation produced success rates in the living sample between 83.9 and 93.5%; the distal shaft yielded the highest results. Success rates were lower among the prehistoric test sample, with better results (83.3%) for the mid-Holocene population (farmers and herders) than for earlier groups (e.g., hunter-gatherers; < 60%). These results were compared with those obtained using other methods for sex estimation based on various skeletal elements. This study provides new, reliable, and simple methods with high success rates for sex estimation based on femoral CSG variables obtained automatically from CT images. Discriminant functions were created for various conditions of femoral completeness. However, these functions should be used carefully in past populations from different settings.


Rhegmatogenous retinal detachment in Coats' disease: a case report.
Coats' disease was originally defined as a unilateral idiopathic exudative retinopathy in young males, characterized by abnormal retinal vascular telangiectasia with intraretinal and subretinal lipid exudation. The retinal detachment is usually exudative. Herein, we describe a case of rhegmatogenous retinal detachment with detectable retinal break in a patient with Coats' disease. A 15-year-old Indo-Aryan male patient presented with sudden painless diminution of vision in his right eye of 4 days duration. Upon examination, the anterior segment in both eyes and left fundus was within normal limits. Dilated fundus evaluation of the right eye revealed telangiectasia of the retinal vessels, with subretinal exudation in superotemporal and superonasal quadrants and presence of subretinal fluid in the superotemporal area extending into fovea. There was also presence of single flap horseshoe tear in the superotemporal quadrant at around the 10 o'clock position in the equatorial region, with no secondary changes. The retina was reattached with encircling band buckle combined with vitrectomy and silicon oil tamponade. Seven months post vitrectomy, lenticular opacification developed, for which he underwent silicon oil removal, along with lens aspiration and implantation of foldable intraocular lens. Over the period of 1 year, his best corrected visual acuity improved from 6/60 to 6/18 in the affected eye at the last follow-up visit. The recovery was uneventful following the subsequent surgery. Coats' disease has a remarkable diversity in clinical presentation and morphology. The disease can also present with an underlying break, which may not be attributed to any iatrogenic modality. The treatment modalities in coats' disease should be tailored individually due to the low incidence of the disease and the great variation in severity upon presentation. Prompt management restores the best possible anatomical outcome and maintains good vision.


Rhegmatogenous retinal detachment following intravitreal ocriplasmin.
To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection. Retrospective, multi-centre, observational case series with case note review. Eight patients with symptomatic vitreomacular traction (six with concomitant macular hole) were diagnosed with RRD after a median of 16 days (range 3-131 days) post-OCP injection. Presentation was within 3 weeks of the OCP injection in six of the cases. Five patients presented with symptoms post-OCP, and three were diagnosed asymptomatically on planned visits. Seven cases were phakic, one had high myopia (>8 dioptres), and two cases had lattice degeneration. Following RRD surgery, hole closure was achieved in 5/6 MH cases. The final median BCVA at 7 months was 20/80 (range 20/40-20/1200) similar to the baseline BCVA 20/80, with four patients gaining ≥1 line of vision compared to baseline but three losing ≥3 lines. RRD is a non-negligible risk associated with intravitreal OCP, and it should be used with caution in eyes with high myopia and peripheral retinal pathology predisposing to RRD. Detailed peripheral retinal examination is recommended pre- and postoperatively at all visits. Patients should be advised to seek attention if symptoms recur after initial presentation.


Can Students Create Their Own Educational Escape Room? Lessons Learned from the Opioid Crisis Escape Room.
Educational escape rooms (EERs) are live-action, team-based games used to teach content-related and generic knowledge and skills. Instead of students just playing the EER, we believed that giving them the opportunity to create their own EERs would augment the learning effects of this teaching method. We report on the feasibility, evaluation, and lessons learned of our assignment on an opioid epidemic-based EER. This original teaching method appealed to most students, but the workload was evaluated to be too high. Our lessons learned include the need for sufficient (extrinsic) motivation, careful explanation of the assignment, and small group sizes.


The treatment of Stage III nonseminomatous testicular tumors. Roswell Park Memorial Institute results (1970-1979).
A review of 92 patients with Stage III nonseminomatous tumors treated at Roswell Park Memorial Institute between 1970-1979 was undertaken to verify changes in concepts as related to multiple agent chemotherapy and cytoreductive surgery. Each patient had a minimal follow-up of 18 months. Fifty-three patients were seen before 1975. Eighteen had metastasis to the lungs only. These were treated with a variety of single chemotherapeutic agents and cytoreductive surgery. The survival of this group was 38%. Among 35 patients with lung and visceral involvement seen at the same time, only one patient is alive. Thirty-nine patients were seen after 1975 and treated with multi-drug chemotherapy and cytoreductive surgery. The current survival rate of 23 patients with lung metastasis only is 69%. Among 16 patients with lung and visceral involvement, the present survival rate is 31%. This report confirms the effectiveness of multi-drug therapy in conjunction with cytoreductive surgery in the treatment of disseminated testicular tumors.


A comparative study of intraosseous versus peripheral intravenous infusion of diazepam and phenobarbital in dogs.
Authors of recent literature have made several references to the use of intraosseous infusion in emergency situations. This method has provided a useful route of medication and fluid administration when peripheral IV access has been unsuccessful. Controlled studies on intraosseous infusion have been limited. To more accurately evaluate the effectiveness of this technique, we administered diazepam to 20 dogs randomly assigned to either peripheral IV (n = 10) or tibial intraosseous (n = 10) groups. Intramedullary placement usually was performed within 15 seconds. Central venous diazepam samples were collected at one-, three-, six-, ten-, and 20-minute intervals. Intraosseous infusion achieved and maintained serum diazepam levels comparable to those achieved by IV administration. This study was repeated with phenobarbital using a different set of 20 dogs with samples collected at one-, three-, six-, and ten-minute intervals. Results were similar in that the levels were comparable regardless of the use of intraosseous or IV administration. Complications using this technique have been few. When peripheral IV access is unobtainable, intraosseous infusion has been shown to be an effective and efficient alternative for administering medications and fluids.