Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.
Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy. This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion. Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048). Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.


Unusual cases from Dubai, United Arab Emirates.
Dubai is one of the small countries of the United Arab Emirates located on the shores of the Persian Gulf in the Middle East. This report deals with two deaths: one an unusual method of suicide by hanging and the other, a death under investigation into whether it was accidental or suicidal.


Machine Learning in Epidemiology and Health Outcomes Research.
Machine learning approaches to modeling of epidemiologic data are becoming increasingly more prevalent in the literature. These methods have the potential to improve our understanding of health and opportunities for intervention, far beyond our past capabilities. This article provides a walkthrough for creating supervised machine learning models with current examples from the literature. From identifying an appropriate sample and selecting features through training, testing, and assessing performance, the end-to-end approach to machine learning can be a daunting task. We take the reader through each step in the process and discuss novel concepts in the area of machine learning, including identifying treatment effects and explaining the output from machine learning models.


Identification of Acute Malnutrition in Children in Cambodia Requires Both Mid Upper Arm Circumference and Weight-For-Height to Offset Gender Bias of Each Indicator.
Malnutrition remains a serious health problem in Cambodia with over 10% of children less than five years of age suffering from acute malnutrition. In addition to the presence of nutritional edema, two indicators are recommended by the World Health Organization for the diagnosis of acute malnutrition: weight-for-height Z-scores (WHZ; with acute malnutrition defined as WHZ < −2 Z-score) and mid-upper arm circumference (MUAC, with acute malnutrition defined as MUAC < 12.5 cm). Earlier, we showed that WHZ and MUAC identified different subgroups of children with acute malnutrition. To explore factors associated with both indicators of acute malnutrition, we analyzed baseline data from a longitudinal study in three provinces in Cambodia: Phnom Penh (capital, urban environment), Kratie (rural province), and Ratanakiri (hilly, rural province). Data was available for 4381 children below 30 months of age. Malnutrition rates were higher in the two rural provinces than in the capital. Although both MUAC and WHZ showed gender bias, with MUAC identifying more girls, and WHZ identifying more boys with acute malnutrition, the gender effect was strongest for MUAC. The gender bias of MUAC diminished with older age, but remained significant up to 30 months of age. Only using both MUAC and WHZ as indicators resulted in gender neutral identification of acute malnutrition. WHZ alone always identified more children with acute malnutrition than MUAC alone. In Phnom Penh, MUAC alone identified only 11% with acute malnutrition in addition to WHZ. To conclude, both MUAC and WHZ showed gender bias in this cohort of Cambodian children. In Cambodia, implementation of a MUAC-only or a WHZ-only program for the identification of acute malnutrition would be unethical as it will lead to many children remaining undiagnosed.


Master regulators used as breast cancer metastasis classifier.
Computational identification of prognostic biomarkers capable of withstanding follow-up validation efforts is still an open challenge in cancer research. For instance, several gene expression profiles analysis methods have been developed to identify gene signatures that can classify cancer sub-phenotypes associated with poor prognosis. However, signatures originating from independent studies show only minimal overlap and perform poorly when classifying datasets other than the ones they were generated from. In this paper, we propose a computational systems biology approach that can infer robust prognostic markers by identifying upstream Master Regulators, causally related to the presentation of the phenotype of interest. Such a strategy effectively extends and complements other existing methods and may help further elucidate the molecular mechanisms of the observed pathophysiological phenotype. Results show that inferred regulators substantially outperform canonical gene signatures both on the original dataset and across distinct datasets.


Conservation of structural and functional features in a primordial CD80/86 molecule from rainbow trout (Oncorhynchus mykiss), a primitive teleost fish.
In mammals, interaction of CD28 with CD80 or CD86 molecules provides costimulatory signals for T cell activation that leads to increased IL-2 gene and protein expression by activated T cells. Thus far, CD80 and CD86 have been cloned and functionally characterized only in mammals and birds. To shed light into the evolution of CD80 and CD86, we have cloned and functionally characterized a rainbow trout (rt) molecule (rtCD80/86) that shows the highest degree of sequence conservation and phylogenetic relationship with CD80 and CD86 molecules. Moreover, its genomic organization was almost identical to that of human CD86. Rainbow trout possess one membrane-bound and two soluble CD80/86 transcripts, all of which are derived from the same rtCD80/86 gene. The membrane-bound form exhibited its highest degree of expression in lymphoid tissues, particularly on B cells. Incubation of trout leukocytes with LPS and bacteria leads to up-regulation of rtCD80/86 gene expression. Importantly, we show that trout and other teleost fish contain a single CD80/86 gene, thus suggesting that this gene may represent the ancestor from which CD80 and CD86 arose by gene duplication in more evolved species. To gain further insights into the function of rtCD80/86, we have identified and cloned trout IL-2 and have shown that recombinantly produced trout CD80/86 up-regulates the expression of IL-2 in trout blood leukocytes. Significantly, this finding indicates that the capacity to modulate IL-2 expression is a primordial function that has been conserved both in fish and mammalian CD80/CD86 molecules throughout 350 million years of evolution.


Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes: A Randomized Controlled Trial.
To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes. We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (β error 0.20, two-sided α error 0.05). Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.60-1.22, P=.39). In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion. NTR Dutch Trial Register, NTR3492.


Role of s-100 immunostaining in demonstration of nerve changes and quantification of dendritic cells in leprosy.
A definitive diagnosis of leprosy is based on a demonstration of either acid-fast bacilli or nerve elements within the granulomas. On routine hematoxylin and eosin stains, the nerve fibers are not easily identifiable. In this study, S-100 immunostain is used to highlight the nerve elements and to demonstrate and compare the nerve changes in spectrum of leprosy including reactions. To demonstrate the nerve changes in spectrum of leprosy using S-100 immunostaining so as to categorize them for the purpose of early diagnosis and treatment. We also want to demonstrate and quantify the dendritic cells in lepromatous spectrum of leprosy using S-100 immunostain. Twenty consecutive skin biopsy specimens from patients with histopathological diagnosis of leprosy in the year 2012 were studied. Of these 20 cases, 13 were Borderline Tuberculoid, 1 was of indeterminate leprosy, 1 Borderline Lepromatous, 2 cases of Lepromatous Lep-rosy , 1 case of Type 1 reac-tion and 2 cases of Type 2 reaction. Stains used were Hematoxylin and Eosin stain for the histopathological diagnosis, Fites stain for Bacillary index and S-100 immunoperoxidase staining for nerve changes. 5 cases of granulomatous dermatosis of skin other than leprosy (5 cases of lupus vulgaris) were included as controls. On Hematoxylin and Eosin staining, the nerve fibers showed vertical orientation in relation to epidermis in Borderline Tuberculoid leprosy. In addition , the nerve fibers showed rounded contour in Tuberculoid leprosy. The entire spectrum of leprosy showed evidence of nerve damage in S-100 immunostaining which was categorized in 4 patterns 1. Absent, 2. Fragmented, 3. Discontinuous and 4. Intact. The majority of Borderline Tuberculoid leprosy cases showed absent pattern of nerve damage. Dendritic cells were also positive for S-100 immunostaining with granular positivity in Borderline Tuberculoid Leprosy cases and membranous positivity in Lepromatous spectrum. Nerve damage is seen across the entire spectrum of leprosy and the early identification of this nerve damage using S-100 immunostaining, helps to differentiate between Lepromatous and Tuberculoid leprosy, especially in the borderline and indeterminate forms.


Fatal interstitial lung disease after addition of sorafenib to a patient with lung adenocarcinoma who had failed to improve with erlotinib alone.
Interstitial lung disease (ILD) induced by epidermal growth factor receptor tyrosine kinase inhibitors has been extensively documented with decreasing incidence after appropriate patient selection due to increasing awareness over the years. However, ILD induced by sorafenib was mentioned with lower frequency only in patients with hepatocellular and renal cell carcinoma living in Japan but not in patients with other carcinomas or living outside Japan, and it has been overlooked in clinical practice. In the present case, sorafenib was added to the treatment of a 60-year-old non-smoking patient with non-small cell lung cancer (NSCLC). After his failing to improve with erlotinib alone, erlotinib was continued to be given in combination with sorafenib as a salvage therapy. Although clinical signs of ILD were observed 2 weeks after the addition of sorafenib, the radiological diagnosis of ILD was only made 41 days after the initiation of the combination treatment, and the patient died 56 days after treatment onset. It was concluded that ILD was indeed induced by sorafenib. This is the first report of ILD induced by sorafenib in a patient with NSCLC living outside Japan. Oncologists should be aware of this fatal complication for its early detection in order to avoid a severe course of ILD leading to a decrease in the ILD mortality rate.


Direct measurement of inositol in bovine myelin basic protein.
Myelin basic protein has been isolated from bovine central-nervous-system myelin by four methods, none of which exposes the protein to acid. After purification the inositol content of both hydrolysed and unhydrolysed protein was quantified by g.c.-m.s. Basic protein prepared by all methods contained less than 4 mol % of inositol. It is concluded, contrary to a previous proposal, that covalent binding to phosphoinositides does not represent a general mechanism for attachment of this cytoplasmically-oriented protein to its membrane.


Impact of sarcopenia on the survival of patients undergoing liver transplantation for decompensated liver cirrhosis.
Patients with decompensated cirrhosis (DC) are prone to skeletal muscle loss, namely, sarcopenia, before liver transplantation (LT). While sarcopenia is reportedly associated with adverse outcomes after LT, these findings are limited owing to mixed diseases and retrospective data. We investigated the association between sarcopenia and 1-year overall survival (OS) in patients with DC after LT and established and validated a prediction model for postoperative OS based on sarcopenia. Overall, 222 consecutive patients who underwent LT at our centre were registered between September 2020 and June 2022. Third lumbar spine skeletal muscle mass index was measured using computed tomography. Patients were divided into sarcopenia and non-sarcopenia groups according to the skeletal muscle mass index, and baseline data and postoperative outcomes were collected, compared and analysed. The primary outcome was the 1-year OS after LT. We established a dynamic nomogram of the OS predictive model. We included 177 DC patients [mean (standard deviation) age, 50.2 ± 9.3 years; 52 women (29.4%)]; 73 (41.2%) had sarcopenia. The mean (standard deviation) body mass index was 22.6 ± 4.5 kg/m2 , 28 (15.8%) patients had weight loss ≥5% within 6 months before admission, and the mean (standard deviation) model for end-stage liver disease (MELD) score was 18.4 ± 7.9. Patients with sarcopenia had a longer duration of intensive care unit stay (4.1 ± 2.2 vs. 3.1 ± 1.1 days, P = 0.008), higher rate of major complications (45.2% vs. 22.1%, P = 0.001) and higher postoperative mortality (15.1% vs. 2.9%, P = 0.003) than those without sarcopenia. The median 1-year OS after surgery was shorter in patients with sarcopenia than in those without (P < 0.001). Sarcopenia [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.54-5.63; P = 0.022], weight loss ≥5% (HR, 2.46; 95% CI, 1.39-5.09; P = 0.015) and MELD score (HR, 1.05; 95% CI, 1.01-1.09; P = 0.009) were independent risk factors associated with 1-year OS. The area under the curve of the established dynamic nomogram was 0.774, the calibration curve showed good consistency, and analysis of the decision curve showed more clinical benefits than the MELD score alone. High-risk patients (>102.9 points calculated using the nomogram) had a significantly reduced survival rate. Sarcopenia is associated with adverse outcomes after LT in patients with DC. High-risk patients should be classified by dynamic nomogram upon admission.


The molecular and clinical role of Tensin 1/2/3 in cancer.
Tensin 1 was originally described as a focal adhesion adaptor protein, playing a role in extracellular matrix and cytoskeletal interactions. Three other Tensin proteins were subsequently discovered, and the family was grouped as Tensin. It is now recognized that these proteins interact with multiple cell signalling cascades that are implicated in tumorigenesis. To understand the role of Tensin 1-3 in neoplasia, current molecular evidence is categorized by the hallmarks of cancer model. Additionally, clinical data involving Tensin 1-3 are reviewed to investigate the correlation between cellular effects and clinical phenotype. Tensin proteins commonly interact with the tumour suppressor, DLC1. The ability of Tensin to promote tumour progression is directly correlated with DLC1 expression. Members of the Tensin family appear to have tumour subtype-dependent effects on oncogenesis; despite numerous data evidencing a tumour suppressor role for Tensin 2, association of Tensins 1-3 with an oncogenic role notably in colorectal carcinoma and pancreatic ductal adenocarcinoma is of potential clinical relevance. The complex interplay between these focal adhesion adaptor proteins and signalling pathways are discussed to provide an up to date review of their role in cancer biology.


A VR-based Treadmill Training System for Post-stroke Gait Rehabilitation.
Virtual reality (VR) has the potential to enhance rehabilitation by creating simulated multiple training environments, thereby maximizing the implementation of motor learning principles. However, previous use of VR-based treadmill training to improve post-stroke gait function is limited by high cost and a lack of adherence to post-stroke gait rehabilitation principles in system design. This paper describes the development of a gait rehabilitation system that integrates treadmill gait training with VR technology to create a virtual rehabilitation setting with gait training tasks and real-time performance feedback. The proposed system targets post-stroke patients and integrates low-cost sensor and rehabilitation principles to allow remote training and maximize training efficacy.Clinical Relevance-This system is developed with an emphasis on rehabilitation and motor learning principles.


Football Fans' Emotions: Uncertainty Against Brand Perception.
Football is an industry driven by emotions. Fans experience many different emotions related to their teams. This paper aims to inspect how emotions impact attendance at football matches, examining whether football fans prefer to watch highly competitive matches or matches between good teams with star-players. The paper also considers behavioral and emotional differences of match spectators when brand-teams play away or at home. Importantly, we are also looking for the effects that the expectations of these emotions have on the tickets' price mechanism. We use data from three seasons of the Brazilian State championship with information on more than 1,100 matches. The OLS estimator with the moderation marginal effects allows for analysis of a brand-team playing with different levels of uncertainty over the outcomes measured by the relative level of the divisions of rivals. We look for the difference between the marginal contribution of the brand-team and the uncertainty of outcomes that might change under some conditions. The analysis is performed later using two subsamples and, finally, we address the problem of endogeneity in price using an instrumental variable. From our results, the main findings are: first, that the price of tickets does not much affect the demand when a brand-team is playing. In case of competitive matches between non-brand-teams, price behavior correlates to the rationality of the demand curve having a negative impact. The fact that price is not relevant for matches with the brand-team comes to corroborate the idea that fans are driven more by emotions than by economic reasoning; second, the phenomena of highly competitive matches does not work when a brand-team is playing against a small one; and third, the effect of a brand-team playing is relatively more important than the uncertainty of outcome. The last two findings mean that the satisfaction of watching star-players or big-teams is stronger than the emotion brought by a competitive match.


[Oxidation of p-nitrobenzylamine and p-dimethylaminomethylbenzylamine by amine oxidases from the human placenta and serum].
Oxidation of p-nitro- and p-dimethylaminomethyl derivatives of benzylamine, catalyzed by amine oxidases from human placenta and blood serum, was studied. The amine oxidase activity was estimated by means of a spectrophotometric procedure involving measurement of aldehyde formed during the reaction after extraction with hexane. For extraction of benzaldehyde and p-nitrobenzaldehyde in the samples HCl was added up to the concentration of 0.17 M and for extraction of p-dimethylaminomethyl benzaldehyde--NaHCO3 up to the 0.5 M concentration. The reaction products were extracted with a yield of 94%, 83% and 78% respectively; molar extinction coefficients for aldehydes at the maximal absorption were equal to 13,080 (241 mn), 16,520 (258 nm), and 11,547 (248 nm), respectively. Analysis of the oxidative reactions using inhibitors Lilly 51,641, deprenyl, aminoguanidine and semicarbazide showed that monoamine oxidase of the A type (95%) and benzylamine oxidase (7%) catalyzed oxidation of 0.1 mM p-nitrobenzylamine in mitochondria and microsomes but oxidation of the substrate at 1 mM concentration was catalyzed by monoamine oxidase of the B type (20% in mitochondria and 35% in microsomes). In the soluble fraction oxidation of p-nitrobenzylamine was catalyzed mainly by diamine oxidase (55%); monoamine oxidase of the A type catalyzed oxidation of 30% of the amine, benzylamine oxidase-15%. The molecular activity of the mitochondrial monoamine oxidase of the A type with p-nitrobenzylamine as a substrate was equal to 61 nmol of the product per 1 mole of the enzyme per 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Wastewater irrigation of salad crops: further evidence for the evaluation of the WHO guidelines.
This paper presents the results of an experiment on salad crop irrigation with waste stabilisation pond effluents, conducted in Southeast Brazil. Over about 18 months several trials were carried out using different effluent qualities to irrigate lettuce, kale, arugula, spinach, and green pepper. Equations for predicting the bacterial quality of irrigated crops (E.coli per gram) based on the irrigation water quality (E.coli per 100 mL) were derived for low and high growing crops. The quantitative microbial risk analysis (QMRA) technique, using pathogen-ingestion scenarios based on these field data and on official statistics of vegetables consumption in Brazil, was used to estimate infection risks arising from the consumption of wastewater irrigated crops. It is inferred that irrigation with effluents complying with the WHO guidelines for unrestricted irrigation should result in salad crops acceptable for consumption.


Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment.
Endometriosis is often associated with a chronic pelvic immuno-inflammatory process, which is closely related to disease pathogenesis and major symptoms. Our studies led to the detection of a marked imbalance between IL-1 and its natural inhibitor IL-1 receptor type 2 (IL1R2) in women with endometriosis. This points to a deficiency in the local control of IL-1 that, in view of the cytokine's elevated levels and potent proinflammatory, angiogenic, and growth-promoting effects, may contribute to endometriosis development. Using an in vivo model in which human endometrial tissue was inoculated into nude mice and left to establish before any further treatment, our data showed that sIL1R2 interferes with the capability of endometrial tissue to invade, grow, disseminate, and stimulate angiogenesis into the host tissue. sIL1R2 significantly down-regulated the expression of major cell adhesion receptors (αv and β3 integrins), matrix metalloproteinases (MMP-2 and -9), and vascular endothelial cell growth factor. Interestingly, treatment with sILR2 (5 μg/kg) led to a concomitant upregulation of matrix metalloproteinases natural inhibitors (TIMP1 and TIMP2) and down-regulation of BclII, a potent anti-apoptotic protein. This creates an imbalance between pro- and anti-proteolytic and apoptotic factors and may further contribute to IL1R2 growth-inhibitory effects. This study provides evidence that sIL1R2 alters ectopic endometrial tissue growth, remodeling, and survival in vivo and may represent an interesting potential therapeutic tool.


IR and Raman spectra of liquid water: theory and interpretation.
IR and Raman (parallel- and perpendicular-polarized) spectra in the OH stretch region for liquid water were measured some years ago, but their interpretation is still controversial. In part, this is because theoretical calculation of such spectra for a neat liquid presents a formidable challenge due to the coupling between vibrational chromophores and the effects of motional narrowing. Recently we proposed an electronic structure/molecular dynamics method for calculating spectra of dilute HOD in liquid D(2)O, which relied on ab initio calculations on clusters to provide a map from nuclear coordinates of the molecules in the liquid to OH stretch frequencies, transition dipoles, and polarizabilities. Here we extend this approach to the calculation of couplings between chromophores. From the trajectories of the fluctuating local-mode frequencies, transition moments, and couplings, we use our recently developed time-averaging approximation to calculate the line shapes. Our results are in good agreement with experiment for the IR and Raman line shapes, and capture the significant differences among them. Our analysis shows that while the coupling between chromophores is relatively modest, it nevertheless produces delocalization of the vibrational eigenstates over up to 12 chromophores, which has a profound effect on the spectroscopy. In particular, our results demonstrate that the peak in the parallel-polarized Raman spectrum at about 3250 wavenumbers is collective in nature.


TURIS plasma vaporization--initial Romanian experience with a new technology.
Bipolar electrosurgical approach represents an increasingly acknowledged technology in the treatment of benign prostatic hyperplasia (BPH), and a promising alternative to standard transurethral resection of the prostate (TURP). In this study, we aimed to evaluate a new method, transurethral resection in saline - plasma vaporization of the prostate (TURIS-PVP), by determining its efficiency, safety and short-term postoperative results. In May 2009, TURIS-PVP was performed in 25 cases of BPH. The investigative protocol included digital rectal examination (DRE), prostatic specific antigen (PSA), International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum flow rate (Qmax) and abdominal ultrasonography assessing prostate volume and post-voiding residual urinary volume (RV). All patients were investigated 1 month after surgery using IPSS, QoL, Qmax and RV. TURIS-PVP was successfully performed in all cases. The average BPH size was 53 ml, the mean operating time was 28 minutes, the median catheterization time was 24 hours and the mean hospital stay was 48 hours. No patient required blood transfusions or re-catheterization, and there were no significant intra- or postoperative complications. Preoperatively, the mean value of IPSS was 21.4, the mean QoL score was 4, the mean RV was 72 ml and the mean Qmax was 9.7 ml/s. The 1 month follow-up emphasized a mean IPSS of 4, a mean QoL score of 1.4, a mean RV of 14 ml and a mean Qmax of 21.5 ml/s. TURIS-PVP represents a valuable endoscopic treatment alternative for patients with BPH, with good efficacy, reduced morbidity, satisfactory follow-up parameters and fast postoperative recovery. IPSS, QoL, Qmax and RV measurements showed significant improvements at the 1 month follow-up.


[Immunotherapy of pulmonary tuberculosis].
The efficiency of treating patients with destructive tuberculosis by using different immune correctors was comparatively analyzed. Five hundred and fifty three patients were treated with thymalin, thymogen, human leukocytic interferon, and a combination of thymogen and interferon. The benefit from immunocorrector treatment was obtained early in the complex therapy and the best result was achieved by the use of thymogen plus interferon. However, the action of the two immunocorrectors increased when fibrous deformity of the lung was healed, followed by the development of pronounced residual changes.


Gene-Controlled Resistance to Acriflavine and Other Basic Dyes in Escherichia coli.
Nakamura, Hakobu (Konan University, Kobe, Japan). Gene-controlled resistance to acriflavine and other basic dyes in Escherichia coli. J. Bacteriol. 90:8-14. 1965.-The genetic determinant controlling the sensitivity of Escherichia coli K-12 W1895 to the basic dyes acriflavine, methylene blue, toluidine blue, crystal violet, methyl green, and pyronine B appears, from results of mating experiments, to be located between the marker governing the utilization of lactose and the origin of genetic transfer. The determinant controlling this resistance to basic dyes does not control resistance to acid dyes. After the introduction of the resistance gene into merozygotes, acriflavine resistance is not established immediately but develops slowly.


Inertial Sensors for Hip Arthroplasty Rehabilitation: A Scoping Review.
The objective of this scoping review is to characterize the current panorama of inertia sensors for the rehabilitation of hip arthroplasty. In this context, the most widely used sensors are IMUs, which combine accelerometers and gyroscopes to measure acceleration and angular velocity in three axes. We found that data collected by the IMU sensors are used to analyze and detect any deviation from the normal to measure the position and movement of the hip joint. The main functions of inertial sensors are to measure various aspects of training, such as speed, acceleration, and body orientation. The reviewers extracted the most relevant articles published between 2010 and 2023 in the ACM Digital Library, PubMed, ScienceDirect, Scopus, and Web of Science. In this scoping review, the PRISMA-ScR checklist was used, and a Cohen's kappa coefficient of 0.4866 was applied, implying moderate agreement between reviewers; 23 primary studies were extracted from a total of 681. In the future, it will be an excellent challenge for experts in inertial sensors with medical applications to provide access codes for other researchers, which will be one of the most critical trends in the advancement of applications of portable inertial sensors for biomechanics.


[Selective muscular atrophy in a family with hereditary myopathy with early respiratory failure].
Hereditary myopathy with early respiratory failure (HMERF) with heterozygous mutations in the titin gene (TTN) is characterized by respiratory failure developing from the early phase of limb weakness or gait disturbance. Here, we describe a characteristic distribution of muscle involvement in three members of a HMERF family with a TTN mutation. Despite the differences in severity exhibited among the father, daughter and son, the systemic imaging studies showed a similar pattern among these individuals. The semitendinosus and fibularis longus muscles were selectively affected, as described previously. In addition, we found marked atrophy in the sternocleidomastoid and psoas major muscles, regardless of the disease severity. The atrophy in selective trunk muscles observed in routine CT scans can be useful for the differential diagnosis of hereditary myopathies with heart and respiratory failure.


Efficacy of Over-the-Scope Clips in Management of High-Risk Gastrointestinal Bleeding.
Standard endoscopic therapies do not control bleeding or produce complications in as many as 20% of patients with nonvariceal gastrointestinal bleeding. Most bleeding comes from ulcers with characteristics such as high-risk vascular territories and/or large vessels. We evaluated the efficacy of using over-the-scope clips (OTSCs) as primary or rescue therapy for patients with bleeding from lesions that have a high risk for adverse outcomes. We performed a retrospective analysis of data from 67 patients with gastrointestinal bleeding from high-risk lesions who were treated with OTSCs as primary (n = 49) or rescue therapy (n = 18) at a quaternary center, from December 2011 through February 2015. The definition of high-risk lesions was lesions that were situated in the area of a major artery and larger than 2 mm in diameter and/or a deep penetrating, excavated, fibrotic ulcer with high-risk stigmata, in which a perforation could not be ruled out or thermal therapy would cause perforation, or lesions that could not be treated by standard endoscopy. Clinical severity was determined based on the Rockall score and a modified Blatchford score. Our primary outcome was the incidence of rebleeding within 30 days after OTSC placement. We assessed risk factors for rebleeding using univariate hazard models followed by multivariable analysis. Of the 67 patients, 47 (70.1%) remained free of rebleeding at 30 days after OTSC placement. We found no difference in the proportion of patients with rebleeding who received primary or rescue therapy (hazard ratio, 0.639; 95% confidence interval, 0.084-4.860; P = .6653). Only 9 rebleeding events were linked clearly to OTSCs and required intervention, indicating an OTSC success rate of 81.3%. We found no significant associations between rebleeding and clinical scores. However, on multivariable analysis, patients with coronary artery disease had a higher risk of rebleeding after OTSC independent of international normalized ratio and antiplatelet use (hazard ratio, 7.30; P = .0002). In a retrospective analysis of 67 patients with bleeding from high-risk gastrointestinal lesions, we found OTSCs to prevent rebleeding in more than 80% of cases. In the past, these lesions were treated with surgical or radiologic interventions. Patients with coronary artery disease have an increased risk of rebleeding after OTSCs, suggesting the need for escalated therapies.


Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations (Part 1).
This Enhanced Recovery After Surgery (ERAS) Guideline for perioperative care in cesarean delivery will provide best practice, evidenced-based, recommendations for preoperative, intraoperative, and postoperative phases with, primarily, a maternal focus. The focused pathway process for scheduled and unscheduled cesarean delivery for this ERAS Cesarean Delivery Guideline will consider from the time from decision to operate (starting with the 30-60 minutes before skin incision) to hospital discharge. The literature search (1966-2017) used Embase and PubMed to search medical subject headings that included "Cesarean Section," "Cesarean Section," "Cesarean Section Delivery" and all pre- and intraoperative ERAS items. Study selection allowed titles and abstracts to be screened by individual reviewers to identify potentially relevant articles. Metaanalyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series were considered for each individual topic. Quality assessment and data analyses that evaluated the quality of evidence and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation system, as used and described in previous ERAS Guidelines. The ERAS Cesarean Delivery Guideline/Pathway has created a maternal focused pathway (for scheduled and unscheduled surgery starting from 30-60 minutes before skin incision to maternal discharge) with ERAS cesarean delivery consensus recommendations preoperative elements (anesthetic medications, fasting, carbohydrate supplementation, prophylactic antibiotics/skin preparation, ), intraoperative elements (anesthetic management, maternal hypothermia prevention, surgical technique, hysterotomy creation and closure, management of peritoneum, subcutaneous space, and skin closure), perioperative fluid management, and postoperative elements (chewing gum, management of nausea and vomiting, analgesia, timing of food intake, glucose management, antithrombotic prophylaxis, timing of ambulation, urinary management, and timing of maternal and neonate discharge). Limited topics for optimized care and for antenatal education and counselling and the immediate neonatal needs at delivery are discussed. Strong recommendations for element use were given for preoperative (antenatal education and counselling, use of antacids and histamine, H2 receptor antagonists, 2-hour fasting and small meal within 6 hours surgery, antimicrobial prophylaxis and skin preparation/chlorhexidine-alcohol), intraoperative (regional anesthesia, prevention of maternal hypothermia [forced warm air, warmed intravenous fluids, room temperature]), perioperative (fluid management for euvolemia and neonatal immediate care needs that include delayed cord clamping), and postoperative (fluid management to prevent nausea and vomiting, antiemetic use, analgesia with nonsteroidal antiinflammatory drugs/paracetamol, regular diet within 2 hours, tight capillary glucose control, pneumatic compression stocking for venous thromboembolism prophylaxis, immediate removal of urinary catheter). Recommendations against the element use were made for preoperative (maternal sedation, bowel preparation), intraoperative (neonatal oral suctioning or increased inspired oxygen), and postoperative (heparin should not be used routinely venous thromboembolism prophylaxis). Because these ERAS cesarean delivery pathway recommendations (elements/processes) are studied, implemented, audited, evaluated, and optimized by the maternity care teams, this will create an opportunity for the focused and optimized areas of care research with further enhanced care and recommendation.


Neutral amino acid influx in developing rabbit blastocysts.
The influx of the neutral amino acids glycine, aminoisobutyric acid (AIB), and leucine into rabbit blastocysts was measured. In day 6 postcoitus (pc) embryos, glycine influx was Na+ independent, whereas AIB and leucine influx involved both Na+-dependent and independent components. From days 5 to 7 pc, the leucine and AIB influx remained constant, although the Na+-dependent fraction decreased and the Na+-independent fraction increased with age. None of the Na+-independent influx was inhibited by methylaminoisobutyric acid (MeAIB), an amino acid analogue specific for the system A of neutral amino acid uptake. In addition, MeAIB influx was Na+ independent, implying that system A is not involved in leucine or AIB uptake. All Na+-dependent influx is thus considered to occur via system ASC. System L contributed only to the influx of leucine at days 6 and 7 pc, as measured by inhibition of Na+-independent influx by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid.


Lymphocyte responses to virus and mitogen in ponies during experimental infection with equine herpesvirus 1.
Six pony foals, experimentally infected with equine herpesvirus 1 (EHV-1), were studied for their lymphocyte responses to EHV-1 and phytohemagglutinin (PHA) stimulations. Lymphocyte blastic transformation in the presence of EHV-1 appeared as early as 2 days after the foals were inoculated, reached a peak in 7 to 10 days, and subsequently decreased. In contrast, the lymphocyte blastic transformation in the presence of PHA increased sharply, reaching a peak in 2 to 3 days, and then decreased to its lowest level in 10 days after which it returned to its near preinoculation level. As for the mechanism of the transient hyporesponsiveness to mitogen, sera from the ponies after inoculation did not cause lessened stimulatory response of normal lymphocytes to PHA. The possible mechanism of this transient hyporesponsiveness to mitogen is discussed.


Toxicity and metabolism of pyrrolizidine alkaloids.
Pyrrolizidine alkaloids (PA) are found mainly in plants of three families: boraginaceae, Compositae and Leguminosae. In North America, PA poisoning of livestock is caused primarily by consumption of Senecio and Crotalaria spp. The PA of Senecio spp. cause irreversible hepatic damage; toxicity signs are a consequence of impaired liver function. Crotalaria intoxication leads to pulmonary damage as a primary effect; hepatic effects are less prominent. Large species differences exist in susceptibility to PA toxicosis. Small herbivores such as sheep, goats, rabbits, guinea pigs and other herbivorous laboratory animals are highly resistant to PA toxicity, associated with a low rate of hepatic production of reactive metabolites (pyrroles) and(or) a high rate of activity of detoxifying enzymes. Diester PA common to Heliotropium and Echium spp. are metabolized in the ovine rumen to 1-methyl metabolites, whereas the macrocyclic ester PA of Senecio spp. are not. Exposure to PA results in high concentrations of liver Cu, reduced liver Zn, and abnormal Fe metabolism with hematopoiesis markedly impaired. Pyrrolizidine alkaloid toxicity alters vitamin A metabolism in rats, depressing plasma and liver levels of vitamin A. Synthetic antioxidants in the diet confer protective activity in laboratory animals (e.g., rats, mice) against PA toxicoses. The PA and their metabolites are secreted in the milk of lactating animals, but this probably does not represent a significant human health hazard.


Detection of IgE anti-parvovirus B19 and increased CD23+ B cells in parvovirus B19 infection: relation to Th2 cytokines.
The immune profile of a parvovirus B19-infected patient (male, 8 years old) was studied on day 0 (initial presentation) and on days 14 and 210 post symptom presentation (psp). Before infection, the patient was skin test positive to various allergens, including ragweed and tree and grass pollens, and had a serum IgE level of 150 IU/mL. On day 0, the patient was diagnosed as parvovirus B19 infected, as judged by the presence of IgG anti-parvovirus Abs in serum (EIA) and presentation of "slap cheek" rash. The patient's serum IgE level increased from 150 IU/mL before infection to 256 IU/mL on day 0, was 233 IU/mL on day 14, and returned to preinfection levels on day 210. In contrast, there was little change in the levels of serum IgM, IgG, or IgA (nephelometry). IgE anti-parvovirus B19 protein (VP-N) was detected in serum (Western blot) on days 0, 14, and 210, despite the decrease in total IgE on day 210. Although there was no increase in total numbers of blood CD23+ B cells on day 0, by day 14 the numbers of these cells increased dramatically (93%), remaining high on day 210. In contrast, there were virtually no changes in total numbers of CD4+ and CD8+ T cells or CD16/56+ NK precursor cells on days 0-210. On day 0, when IgG and IgE anti-parvovirus were detected in serum, patient's peripheral blood mononuclear cells (PBMC) expressed mRNA for the Th2 cytokines IL-4 and IL-10, but not for the Th1 cytokines IFN-gamma or IL-2. However, by day 14 psp, PBMC expressed mRNA for the Th1 cytokines IFN-gamma and IL-2, as well as for IL-4 and IL-10. This is the first demonstration of the existence of IgE anti-parvovirus B19 Ab. The presence of IgE anti-parvovirus B19 Ab in serum on day 0 and its persistence in serum 7 months psp suggests that IgE anti-parvovirus may be useful in prognosis of parvovirus B19 infection. Our results reinforce the idea that IgE, in general, may play a major role in anti-viral immunity, perhaps in conjunction with CD23+ cells. The results further suggest that clearance of this infection is accompanied by a switch to Th1 cytokines.


Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription.
Quorum sensing has been implicated as an important global regulatory system controlling the expression of numerous virulence factors in bacterial pathogens. SmcR, a homologue of Vibrio harveyi LuxR, has been proposed as a quorum-sensing master regulator of Vibrio vulnificus, an opportunistic human pathogen. Previous studies demonstrated that SmcR is essential for the survival and pathogenesis of V. vulnificus, indicating that inhibiting SmcR is an attractive approach to combat infections by the bacteria. Here, we determined the crystal structure of SmcR at 2.1 A resolution. The protein structure reveals a typical TetR superfamily fold consisting of an N-terminal DNA binding domain and a C-terminal dimerization domain. In vivo and in vitro functional analysis of the dimerization domain suggested that dimerization of SmcR is vital for its biological regulatory function. The N-terminal DNA recognition and binding residues were assigned based on the protein structure and the results of in vivo and in vitro mutagenesis experiments. Furthermore, protein-DNA interaction experiments suggested that SmcR may have a sophisticated mechanism that enables the protein to recognize each of its many target operators with different affinities.


RP4-mediated conjugation in Acinetobacter calcoaceticus.
The P class R factor RP4 was transferred from Escherichia coli K12 to Acinetobacter calcoaceticus. RP4 conferred similar levels of antibiotic resistance in A. calcoaceticus to those in the E. coli K12 donor. Only slight instability of RP4 in A. calcoaceticus was detected. Transfer of RP4 between strains of A. calcoaceticus was by conjugation and was accompanied by transfer of chromosomal genes. Possible polarity of marker transfer was observed and linkage between a number of chromosomal markers was demonstrated.


[New aspects of the activities of pediatric intensive care unit].
A model of regional network of pediatric resuscitation has been created in the Sverdlovsk region. The model is based on evaluation of hazards, is staged, standard, and makes use of a universal information space. The unifying structure is a pediatric resuscitation consultation center. Its main tasks are therapy and counseling in the region and introduction of overall training in reanimation and intensive care of children, with improvement of the level of urgent care at therapeutic institutions of the region. The activities of the resuscitation care network promoted a significant decrease in neonatal mortality by 29.5% and of infant mortality by 28.7%.


[Hordein locus polymorphism in near eastern local populations of cultivated barley (Hordeum vulgare L.)].
Electrophoresis in starch gel has been used to study the polymorphism of hordeins encoded by loci Hrd A, Hrd B, and Hrd F in 140 local barley populations from the Near East, including 60, 34, 33, 8, and 5 populations from Syria, Jordan, Iraq, Palestine, and Israel, respectively. Fifty-seven Hrd A, 87 Hrd B, and 5 Hrd F alleles have been found. The alleles of these loci considerably differ in frequencies and distribution in populations from different Near Eastern countries. Cluster analysis of the matrix of the frequencies of hordein locus alleles in barley populations from the Near East, North Africa, Ethiopia, and South Arabia has yielded two clusters. The first cluster includes barley populations from Israel, Palestine, Morocco, Tunisia, Algeria, and Egypt; the second cluster, populations from Iraq, Syria, Jordan, Yemen, and Ethiopia.


Non-Contact Infrared Thermometers and Thermal Scanners for Human Body Temperature Monitoring: A Systematic Review.
In recent years, non-contact infrared thermometers (NCITs) and infrared thermography (IRT) have gained prominence as convenient, non-invasive tools for human body temperature measurement. Despite their widespread adoption in a range of settings, there remain questions about their accuracy under varying conditions. This systematic review sought to critically evaluate the performance of NCITs and IRT in body temperature monitoring, synthesizing evidence from a total of 72 unique settings from 32 studies. The studies incorporated in our review ranged from climate-controlled room investigations to clinical applications. Our primary findings showed that NCITs and IRT can provide accurate and reliable body temperature measurements in specific settings and conditions. We revealed that while both NCITs and IRT displayed a consistent positive correlation with conventional, contact-based temperature measurement tools, NCITs demonstrated slightly superior accuracy over IRT. A total of 29 of 50 settings from NCIT studies and 4 of 22 settings from IRT studies achieved accuracy levels within a range of ±0.3 °C. Furthermore, we found that several factors influenced the performance of these devices. These included the measurement location, the type of sensor, the reference and tool, individual physiological attributes, and the surrounding environmental conditions. Our research underscores the critical need for further studies in this area to refine our understanding of these influential factors and to develop standardized guidelines for the use of NCITs and IRT.


Power comparisons between similarity-based multilocus association methods, logistic regression, and score tests for haplotypes.
Recently, a genomic distance-based regression for multilocus associations was proposed (Wessel and Schork [2006] Am. J. Hum. Genet. 79:792-806) in which either locus or haplotype scoring can be used to measure genetic distance. Although it allows various measures of genomic similarity and simultaneous analyses of multiple phenotypes, its power relative to other methods for case-control analyses is not well known. We compare the power of traditional methods with this new distance-based approach, for both locus-scoring and haplotype-scoring strategies. We discuss the relative power of these association methods with respect to five properties: (1) the marker informativity; (2) the number of markers; (3) the causal allele frequency; (4) the preponderance of the most common high-risk haplotype; (5) the correlation between the causal single-nucleotide polymorphism (SNP) and its flanking markers. We found that locus-based logistic regression and the global score test for haplotypes suffered from power loss when many markers were included in the analyses, due to many degrees of freedom. In contrast, the distance-based approach was not as vulnerable to more markers or more haplotypes. A genotype counting measure was more sensitive to the marker informativity and the correlation between the causal SNP and its flanking markers. After examining the impact of the five properties on power, we found that on average, the genomic distance-based regression that uses a matching measure for diplotypes was the most powerful and robust method among the seven methods we compared.


Immunosuppression in the sensitized heart transplant recipient.
The proportion of heart transplant candidates who are allosensitized has increased over time. Advances in tissue typing and immunosuppression have improved the rate of successful transplant in this challenging population. Recently published data regarding contemporary approaches to desensitization prior to and immunosuppression following transplant are summarized. Continued progress in measurement and characterization of antibodies and strategies to abrogate antibody production both prior to and following heart transplant have been encouraging. Updates on the role of non-human leukocyte antigen antibodies and the impact of mechanical circulatory support on allosensitization are provided. Data on current desensitization strategies, including the increasing use of monoclonal antibodies, are provided and the potential role of complement inhibitors will be reviewed. Increasing experience with potent novel agents is likely to provide the opportunity to improve transplant outcomes for highly sensitized patients. Although allosensitized heart transplant candidates remain a management challenge, excellent outcomes can be achieved with contemporary approaches. Advances in the understanding of B-cell biology are anticipated to further broaden options and improve outcomes.


Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice.
Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. We created MI in 12- to 16-week-old, male Prx-3-transgenic mice (TG+MI, n=37) and nontransgenic wild-type mice (WT+MI, n=39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TG+MI than in WT+MI mice (mean+/-SEM, 1.5+/-0.2 vs 2.2+/-0.2 nmol/mg protein; n=8 each, P<0.05). LV cavity dilatation and dysfunction were attenuated in TG+MI compared with WT+MI mice, with no significant differences in infarct size (56+/-1% vs 55+/-1%; n=6 each, P=NS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TG+MI mice were also larger than those in WT+sham-operated mice but smaller than those in WT+MI mice. Improvement in LV function in TG+MI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WT+MI mice, and this decrease was also ameliorated in TG+MI mice. Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.


The Role of Nutrition in Pathogenesis of Uterine Fibroids.
Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women's quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.


Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome.
Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation. Two conflicting hypotheses on the requirement for dimer displacement are that nucleosomal DNA needs to be unwrapped before a dimer can displace and that a dimer can displace without DNA unwrapping. In order to test the hypotheses, we employed three-color single-molecule FRET and monitored in a time-resolved manner the early kinetics of H2A-H2B dimer dissociation triggered by high salt concentration and by histone chaperone Nap1. The results reveal that dimer displacement requires DNA unwrapping in the vast majority of the nucleosomes in the salt-induced case, while dimer displacement precedes DNA unwrapping in >60% of the nucleosomes in the Nap1-mediated case. We also found that acetylation at histone H4K16 or H3K56 affects the kinetics of Nap1-mediated dimer dissociation and facilitates the process both kinetically and thermodynamically. On the basis of these results, we suggest a mechanism by which histone chaperone facilitates H2A-H2B dimer displacement from the histone core without requiring another factor to unwrap the nucleosomal DNA.


Minimally invasive sacroiliac fixation in oncologic patients with sacral insufficiency fractures using a fluoroscopy-based navigation system.
Surgical technique article with retrospective case series. Sacral insufficiency fractures are commonly encountered in oncologic patients and constitute a cause for persistent lower back and pelvic pain. The aim of this study is to describe the modified technique of navigated percutaneous sacroiliac (SI) fixation using multiple long screws per level that cross both SI joints and engage bilateral iliac bones; furthermore to evaluate its safety and efficacy in oncologic patients with sacral insufficiency fractures. Six oncologic patients (3 male, 3 female, mean age: 58.8 y) with sacral insufficiency fractures who had undergone additional radiation therapy were operated with navigated percutaneous fixation. Two patients had failed preoperative sacroplasty and 1 had failed SI pinning. Eighteen SI screws were placed (15 at S1 level and 3 at S2). In the majority of cases the screws were long enough to engage bilateral ilium and sacrum. Additionally, 1 patient underwent percutaneous iliolumbar instrumentation and in 4 patients we performed concomitant sacroplasty or polymethylmethacrylate screw augmentation. The patients were followed for 18.8 months in average (range: 12-30 mo). Outcome was assessed using the Karnofsky Performance Status score (KPS), pain scale (0-10) and detailed neurologic examination. In 1 case, a revision of a screw was required due to radiculopathy. There was no perioperative morbidity or mortality. No hardware failure was encountered. There was significant improvement in KPS (P=0.04) and pain levels (P=0.02). These preliminary data suggest that navigated percutaneous SI screw fixation is a safe and effective intervention in terms of pain control and performance status improvement in oncologic patients with sacral insufficiency fractures. For optimal fixation, multiple long screws that engage both iliac bones may be inserted through the S1 level in a safe manner. The technique may be combined with sacroplasty or closed posterior instrumentation to augment the screw fixation. Further investigation is needed to compare this technique with other treatment modalities.


Sequencing of antiangiogenic agents in the treatment of metastatic colorectal cancer.
Significant advances have been made with respect to our understanding of the critical role of agents targeting angiogenic pathways in the treatment of metastatic colorectal cancer (mCRC). The approval of 3 agents that target angiogenic signaling, bevacizumab, ziv-aflibercept, and regorafenib, provides strong evidence that angiogenesis is an important process in mCRC. The addition of bevacizumab to combination chemotherapy in the first- and second-line treatment of mCRC has resulted in meaningful improvement in overall and progression-free survival. The standard of care for mCRC has evolved to incorporate cytotoxic chemotherapy as the backbone regimens (eg, FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin], FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]) with or without bevacizumab, and epidermal growth factor receptor-targeted therapies (eg, cetuximab, panitumumab) in the setting of wild-type KRAS. The development of ziv-aflibercept in combination with FOLFIRI has improved clinical efficacy in the second-line treatment of mCRC. Regorafenib, a small-molecule multikinase inhibitor, has recently been approved by the US Food and Drug Administration as single-agent therapy in the treatment of refractory and progressive mCRC. Each of these agents has been integrated into an evidence-based-albeit, still evolving-treatment continuum for initial treatment, treatment after first progression, and treatment after second progression. However, the most effective strategy for the use of these agents, and others in development remains unclear. This review provides an overview of the current clinical evidence for the use of antiangiogenic agents targeting in the treatment of mCRC.


Perinatal Chikungunya Virus-associated Encephalitis Leading to Postnatal-Onset Microcephaly and Optic Atrophy.
Chikungunya virus is capable of affecting the nervous system of children and adults. We describe a case of sepsis and encephalitis triggered by this agent in a newborn whose mother developed symptoms of acute infection 2 days before delivery. Consequently, the infant had severe encephalitis that evolved with postnatal-onset microcephaly, bilateral optic atrophy, epilepsy and cerebral palsy.


Diagnosis and classification of optic neuritis.
There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.


[Magnetic resonance angiography of the renal arteries].
Initially, the clinical use of magnetic resonance angiography (MRA) in the abdomen has been restricted because of motion and flow related artifacts. The advent of high performance gradient systems made possible the development of 3D gadolinium-enhanced MRA techniques and expanded the clinical applications of MRA into the abdominal area, particularly for the investigation of renal arteries. This technique is safe, because the administered contrast agent (gadolinium) is free of clinically detectable nephrotoxicity and has a low incidence of allergic reactions. Moreover, contrast MRA also eliminates the risks of ionizing radiation which allows repeating the examination without the accumulation of radiation exposure. The main disadvantages of the technique are its low availability and the fact that the use of contrast agents for this procedure is still not reimbursed by the social security. Many studies demonstrated that contrast MRA allows for the reliable assessment of renal artery morphology and pathologic states. Furthermore, within a single MR examination a comprehensive approach including renal artery morphology, hemodynamic significance of any stenosis and kidney perfusion is available. In this paper, we provide a review of the literature concerning the clinical performance of contrast MRA for the renal arteries and suggest its rationale for the investigation of patients suspected of renovascular disease in our specific environment.


Spatial skills, but not spatial anxiety, mediate the gender difference in number line estimation.
Recently, there has been increasing evidence showing that males estimate whole numbers more accurately than females on the number line. However, relatively little is known about what factors contribute to this gender gap. The current study explored potential mediators of the gender difference in number line estimation, including spatial skills and spatial anxiety. In the Fall (time-point 1 [T1]), 490 children from kindergarten through fourth grade (274 girls) completed age-appropriate measures of number line estimation, spatial skills (including proportional reasoning, mental rotation, mental transformation, and visuospatial working memory), and spatial anxiety. About 5 month later in the Spring (time-point 2 [T2]), children completed the same measure of number line estimation again. Boys were more accurate on number line estimation, proportional reasoning, and mental rotation than girls, whereas girls showed higher levels of spatial anxiety. Critically, spatial skills (a latent variable constructed from proportional reasoning, mental rotation, mental transformation, and visuospatial working memory) at T1 mediated the gender difference in T2 number line estimation whereas spatial anxiety was not a significant mediator. These relationships held even after controlling for T1 number line estimation, reading achievement, and reading anxiety. Among the four spatial skills, proportional reasoning and mental rotation (but not mental transformation or visuospatial working memory) were mediators of the gender difference in T2 number line estimation. These findings constitute, to our knowledge, the first evidence regarding factors contributing to the gender difference in whole number line estimation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Sustainability of Hiking in Combination with Coaching in Cardiorespiratory Fitness and Quality of Life.
Although strong evidence shows that physical inactivity and sedentary behavior are associated with many negative health outcomes, inactive lifestyles are still increasing. Consequently, new approaches must be developed to increase adherence to an active lifestyle and hence a longer life. Green exercise and health coaching could be effective ways to induce long-lasting lifestyle changes geared towards more physical activity. In this randomized controlled trial, we investigated the effects of mountain hiking and psychological coaching on adults with a sedentary lifestyle. The coaching group (n = 26) participated in a 7-day guided hiking program with three personal coaching sessions, whereas the hiking group (n = 32) received no coaching. The effects on aerobic capacity, spirometry and quality of life were assessed at baseline (day 0), after the intervention week (day 7) and after 80 days. Fully nonparametric statistical analysis revealed a gender-based effect for aerobic capacity-the female participants of the coaching group showed a greater improvement (p = 0.03) than the hiking group. No significant effects were found for spirometry. Quality of life parameters improved in both groups. In conclusion, both green exercise and health coaching are capable of inducing improvements in health-related quality of life and cardiorespiratory fitness. No superior effects of health coaching were found.


Protamine alters apical membrane K+ and Cl- permeability in gallbladder epithelium.
Protamine addition to the solution bathing the mucosal side of Necturus gallbladder epithelium (25-100 mg/l) caused depolarization of both cell membranes, a mucosa-negative change in transepithelial voltage, an increase in the apical membrane resistance (Ra) followed by a decrease, and a monotonic increase in transepithelial resistance (Rt). In protamine (25 mg/l), the change in apical membrane voltage elicited by elevating mucosal solution [K+] from 2.5 to 92.5 mM was reduced from 66 +/-2 to 38 +/- 5 mV (P less than 0.001). The K+-induced fall in Ra was also reduced in protamine. These effects could also be elicited by elevating mucosal solution [K+] simultaneously with the addition of protamine and by transient addition of protamine during exposure to the high K+ medium. The effect of protamine on the electrodiffusive Cl- permeability of the apical membrane (PCl) was studied both in control and forskolin-treated tissues. In the absence of forskolin, the hyperpolarization of Vmc produced by lowering mucosal [Cl-] to 10 mM was reversed to a small depolarization; in forskolin, the initial depolarization produced by lowering [Cl-] was significantly increased. Finally, exposure to protamine in the absence of forskolin produced an initial fall in intracellular Cl- activity. Our results indicate that protamine decreases apical membrane K+ permeability and increases apical membrane PCl. The time course of the effects of protamine suggests the possibility of an initial effect on surface potential, followed by secondary actions mediated by intracellular events.


Ligandless ultrasonic-assisted and ionic liquid-based dispersive liquid-liquid microextraction of copper, nickel and lead in different food samples.
A simple and rapid ultrasonic assisted-ionic liquid based-liquid-liquid microextraction (UA-IL-DLLME) method has been developed for the enrichment and separation of Cu(II), Ni(II) and Pb(II). A two level factorial design was used to determine the effect of key factors such as pH, volume of ionic liquid (IL), carbon tetra chloride (CCl4) and sonication time (St). 1-Butyl-3-methylimidazolium hexafluorophosphate ([C4MIM][PF6]) and CCl4 were used as an extractant and dispersant solvent, respectively. The accuracy of the proposed method was evaluated by analysing of SRM Apple Leaves 1515 certified reference material. The limits of detections (LODs) were 0.17 μg/L, 0.49 μg/L and 0.95 μg/L for Cu, Ni and Pb, respectively. The enrichment factor (EF) was 100. The method has been successfully applied for the analysis of the content of Cu, Ni and Pb in spice, vegetable and fruit samples by flame atomic absorption spectrometry (FAAS).


Longitudinal crack propagation in bone around femoral prosthesis.
Intraoperative femoral fracture is a well-recognized technical complication of cementless total hip arthroplasty. This study was designed to establish an in vitro model for initiation and propagation of fractures of the proximal femur in cementless THA and to assess the effect of fracture fixation in the form of cerclage wiring and drilling a hole in the distal extent of the fracture line. Fourteen human anatomic femur specimens were studied. Longitudinal cracks were made and propagation was performed on a materials testing system machine. A drill hole at the tip of a longitudinal crack does not prevent crack propagation. However, cerclage wiring has a statistically significant effect (p less than 0.025) on the ability of the fractured femur to withstand increased load.


Concerns and mental health of teachers from digitally underdeveloped countries regarding the reopening of schools after the first wave of the COVID-19 pandemic.
Torn between the decision to return to school classrooms or continue holding online classes during COVID-19, teachers around the world feel great uncertainty. Bearing in mind that the study of mental health during the pandemic is of great importance for vulnerable categories, and given the role of teachers in society, the aim of this research is to assess teachers' concerns and anxiety before the start of the school year, and also to examine the factors related to them and propose measures in line with the results. The study was conducted as a cross-sectional study before the start of the 2020/2021 school year. The research sample consisted of 286 teachers. For the purposes of this research, a special questionnaire was constructed consisting of a general questionnaire and a Generalized Anxiety Disorder 7-item scale (GAD-7). The strongest predictor of a teacher's answer that they were concerned about the reopening of schools was their concern for their own life and health and for the life and health of their family members, followed by the amount of information received about COVID-19, and, finally, older age. Only 2% of teachers had mild anxiety. This research indicated that it is necessary to examine in more detail the degree of teachers' concern and its impact on their functionality and work process. It is also necessary to repeat the research on the mental health status of teachers and implement procedures in the form of a regular screening program of the mental health status of teachers or implement procedures of support in concern management.


Chemical constituents of Genista numidica Spach aerial parts and their antimicrobial, antioxidant and antityrosinase activities.
A previously undescribed triterpenoid saponin, 3-O-[α-l-rhamnopyranosyl-(1→2)-{β-d-glucopyranosyl-(1→6)-}β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl]-sophoradiol (1), in addition to twenty-nine known constituents (2-30) were isolated from the aerial parts of Genista numidica Spach. Structures elucidation was performed by comprehensive 1D- and 2D-NMR analyses and HRESIMS. The extracts, fractions and isolated compounds were evaluated for their antibacterial, antioxidant and tyrosinase inhibitory activities. The experimental findings indicated that genistin (16), isosalipurpol (27), and koaburaside (29) have moderate to low antibacterial activity against E. faecalis, S. aureus, S. epidermidis and P. aeruginosa bacteria with MICs ranging from 31.2 to 125 μg/mL. Compounds 19 and 27 exhibited a good antiradical activity potential (IC50 11.8 and 11.1 μg/mL, respectively). Only compounds 23, 27 and 28 exhibited low inhibitory effect against mushroom tyrosinase (IC50 from 90.2 to 225.6 μg/mL).


High-speed off-axis Cavity Ring-Down Spectroscopy with a re-entrant configuration for spectral resolution enhancement.
Monitoring of changing samples by Cavity Ring-Down Spectroscopy (CRDS) is possible using fast frequency scans of the laser and/or the cavity resonance. Mode-matched cavity excitation improves performance of fast CRDS but data-points result separated by the cavity Free Spectral Range (FSR): low pressure samples demand long cavities. We demonstrate fast CRDS with off-axis injection of a "re-entrant" resonator yielding FSR/N data-points separation. Our N = 4 short-cavity setup is found to perform well compared with other fast-CRDS implementations. Interestingly, the intrinsic chirped ringing affecting ring-down signals in mode-matched fast-CRDS disappear with off-axis injection. This is due to a fine splitting of the re-entrant-cavity degenerate groups of modes by astigmatism.


Distinct roles of prefrontal cortical subregions in the Iowa Gambling Task.
The Iowa Gambling Task (IGT) assesses decision-making under initially ambiguous conditions. Neuropsychological and neuroimaging data suggest, albeit inconsistently, the involvement of numerous prefrontal cortical regions in task performance. To clarify the contributions of different prefrontal regions, we developed and validated a version of the IGT specifically modified for event-related functional magnetic resonance imaging. General decision-making in healthy males elicited activation in the ventromedial prefrontal cortex. Choices from disadvantageous versus advantageous card decks produced activation in the medial frontal gyrus, lateral orbitofrontal cortex (OFC), and insula. Moreover, activation in these regions, along with the pre-supplementary motor area (pre-SMA) and secondary somatosensory cortex, was positively associated with task performance. Lateral OFC and pre-SMA activation also showed a significant modulation over time, suggesting a role in learning. Striato-thalamic regions responded to wins more than losses. These results both replicate and add to previous findings and help to reconcile inconsistencies in neuropsychological data. They reveal that deciding advantageously under initially ambiguous conditions may require both continuous and dynamic processes involving both the ventral and dorsal prefrontal cortex.


Digital Approaches to Music-Making for People With Dementia in Response to the COVID-19 Pandemic: Current Practice and Recommendations.
Before COVID-19, dementia singing groups and choirs flourished, providing activity, cognitive stimulation, and social support for thousands of people with dementia in the UK. Interactive music provides one of the most effective psychosocial interventions for people with dementia; it can allay agitation and promote wellbeing. Since COVID-19 has halted the delivery of in-person musical activities, it is important for the welfare of people with dementia and their carers to investigate what alternatives to live music making exist, how these alternatives are delivered and how their accessibility can be expanded. This community case study examines recent practice in online music-making in response to COVID-19 restrictions for people with dementia and their supporters, focusing on a UK context. It documents current opportunities for digital music making, and assesses the barriers and facilitators to their delivery and accessibility. Online searches of video streaming sites and social media documented what music activities were available. Expert practitioners and providers collaborated on this study and supplied input about the sessions they had been delivering, the technological challenges and solutions they had found, and the responses of the participants. Recommendations for best practice were developed and refined in consultation with these collaborators. Over 50 examples of online music activities were identified. In addition to the challenges of digital inclusion and accessibility for some older people, delivering live music online has unique challenges due to audio latency and sound quality. It is necessary to adapt the session to the technology's limitations rather than expect to overcome these challenges. The recommendations highlight the importance of accessibility, digital safety and wellbeing of participants. They also suggest ways to optimize the quality of their musical experience. The pandemic has prompted innovative approaches to deliver activities and interventions in a digital format, and people with dementia and their carers have adapted rapidly. While online music is meeting a clear current need for social connection and cognitive stimulation, it also offers some advantages which remain relevant after COVID-19 restrictions are relaxed. The recommendations of this study are intended to be useful to musicians, dementia care practitioners, and researchers during the pandemic and beyond.


Autophagy, inflammation and neurodegenerative disease.
Autophagy is emerging as a central regulator of cellular health and disease and, in the central nervous system (CNS), this homeostatic process appears to influence synaptic growth and plasticity. Herein, we review the evidence that dysregulation of autophagy may contribute to several neurodegenerative diseases of the CNS. Up-regulation of autophagy may prevent, delay or ameliorate at least some of these disorders, and - based on recent findings from our laboratory - we speculate that this goal may be achieved using a safe, simple and inexpensive approach.


Long-Range N-N Bonding by Rydberg Electrons.
By using high-level ab initio methods, we examine the nature of bonding between Rydberg electrons hosted by two four-coordinate nitrogen centers embedded in a hydrocarbon scaffold. The electronic structure of these species resembles that of diradicals, yet the diffuse nature of the orbitals hosting the unpaired electrons results in unusual features. The unpaired Rydberg electrons exhibit long-range bonding interactions, leading to stabilization of the singlet state (relative to the triplet) and a reduced number of effectively unpaired electrons. However, thermochemical gains due to through-space bonding are offset by strong Coulomb repulsion between positively charged nitrogen cores. The kinetic stability of these Rydberg diradicals may be controlled by a judicious choice of the molecular scaffold, suggesting possible strategies for their experimental characterization.


Characterization of oxytocin receptor expression and distribution in the pregnant sheep uterus.
At the end of pregnancy, the myometrium becomes extremely sensitive to oxytocin (OT) as result of a dramatic increase in the number of OT receptors (OTR), indicating an important role for OTR in the process of labor. There are no studies in sheep in which the physical properties and histological distribution of OTR are evaluated in relation to parturition. Also, no studies have been performed in any species to simultaneously examine the distribution of OTR at the messenger RNA (mRNA) as well as the protein levels in the same tissues and correlate those changes with the patterns of myometrial activity that occur at labor. In the present studies, we have used a polyclonal anti-OTR antibody and Western blot analysis to determine the apparent molecular mass of ovine OTR in late pregnant sheep myometrium and endometrium. We also examined the distribution of OTR mRNA and protein expression in the intact myometrium and endometrium and in individual cultured cells using in situ hybridization and immunocytochemistry. The expression of OTR and its mRNA has been correlated with the patterns of activity observed in the pregnant sheep myometrium. Western blot analysis of myometrial and endometrial extracts revealed a major form of OTR with an approximate molecular mass of 66 kDa. Both immunocytochemistry and in situ hybridization localized OTR and its mRNA in myometrial cells and glandular cells of the endometrium. Increased OTR and its mRNA expression in the myometrium and endometrium were correlated with the occurrence of myometrial contractions. OTR was also demonstrated by immunocytochemistry in the smooth muscle of myometrial blood vessels. Localization of OTR and its mRNA in pregnant sheep myometrial cells is consistent with the hypothesis that OTR plays an important role in regulating myometrial contractility. Positive staining of OTR in endometrial glandular cells supports the view that OT is involved in PG production by the endometrium in late pregnancy. Increased expression of OTR and its mRNA in the myometrium during labor further indicates that changes in tissue OTR play a significant role in the mechanism of parturition. Increased expression of OTR and its mRNA in endometrium may relate to the role of OT in regulating PG production by the endometrium during labor.


Constraints and affordances for UK doctors-in-training to exercise agency: A dialogical analysis.
The goal of medical education is to develop clinicians who have sufficient agency (capacity to act) to practise effectively in clinical workplaces and to learn from work throughout their careers. Little research has focused on experiences of organisational structures and the role of these in constraining or affording agency. The aim of this study was to identify priorities for organisational change, by identifying and analysing key moments of agency described by doctors-in-training. This was a secondary qualitative analysis of data from a large national mixed methods research programme, which examined the work and wellbeing of UK doctors-in-training. Using a dialogical approach, we identified 56 key moments of agency within the transcripts of 22 semi-structured interviews with doctors based across the UK in their first year after graduation. By analysing action within the key moments from a sociocultural theoretical perspective, we identified tangible changes that healthcare organisations can make to afford agency. When talking about team working, participants gave specific descriptions of agency (or lack thereof) and used adversarial metaphors, but when talking about the wider healthcare system, their dialogue was disengaged and they appeared resigned to having no agency to shape the agenda. Organisational changes that could afford greater agency to doctors-in-training were improving induction, smoothing peaks and troughs of responsibility and providing a means of timely feedback on patient care. Our findings identified some organisational changes needed for doctors-in-training to practise effectively and learn from work. The findings also highlight a need to improve workplace-based team dynamics and empower trainees to influence policy. By targeting change, healthcare organisations can better support doctors-in-training, which will ultimately benefit patients.


An Intertwined Network of Regulation Controls Membrane Permeability Including Drug Influx and Efflux in Enterobacteriaceae.
The transport of small molecules across membranes is a pivotal step for controlling the drug concentration into the bacterial cell and it efficiently contributes to the antibiotic susceptibility in Enterobacteriaceae. Two types of membrane transports, passive and active, usually represented by porins and efflux pumps, are involved in this process. Importantly, the expression of these transporters and channels are modulated by an armamentarium of tangled regulatory systems. Among them, Helix-turn-Helix (HTH) family regulators (including the AraC/XylS family) and the two-component systems (TCS) play a key role in bacterial adaptation to environmental stresses and can manage a decrease of porin expression associated with an increase of efflux transporters expression. In the present review, we highlight some recent genetic and functional studies that have substantially contributed to our better understanding of the sophisticated mechanisms controlling the transport of small solutes (antibiotics) across the membrane of Enterobacteriaceae. This information is discussed, taking into account the worrying context of clinical antibiotic resistance and fitness of bacterial pathogens. The localization and relevance of mutations identified in the respective regulation cascades in clinical resistant strains are discussed. The possible way to bypass the membrane/transport barriers is described in the perspective of developing new therapeutic targets to combat bacterial resistance.


The influence of operational sex ratio on the intensity of competition for mates.
The evolution and maintenance of secondary sexual characteristics and behavior are heavily influenced by the variance in mating success among individuals in a population. The operational sex ratio (OSR) is often used as a predictor of the intensity of competition for mates, as it describes the relative number of males and females who are ready to mate. We investigate changes in aggression, courtship, mate guarding, and sperm release as a function of changes in the OSR using meta-analytic techniques. As the OSR becomes increasingly biased, aggression increases as competitors attempt to defend mates, but this aggression begins to decrease at an OSR of 1.99, presumably due to the increased costs of competition as rivals become more numerous. Sperm release follows a similar but not significant trend. By contrast, courtship rate decreases as the OSR becomes increasingly biased, whereas mate guarding and copulation duration increase. Overall, predictable behavioral changes occur in response to OSR, although the nature of the change is dependent on the type of mating behavior. These results suggest considerable flexibility of mating system structure within species, which can be predicted by OSR and likely results in variation in the strength of sexual selection.


Early Warning of Acute Altitude Sickness by Physiological Variables and Noninvasive Cardiovascular Indicators.
Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude. Methods One hundred and six Han nationality male individuals were recruited to this research. Dynamic electrocardiogram, treadmill exercise test, echocardiography, routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively. Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness (AMS). Results Approximately 49.05% of the individuals developed AMS. The tricuspid annular plane systolic excursion (22.0±2.66 vs. 23.2±3.19 mm, t=1.998, P=0.048) was significantly lower in the AMS group at sea level, while count of eosinophil [(0.264±0.393)×109/L vs. (0.126±0.084)×109/L, t=-2.040, P=0.045], percentage of differences exceeding 50 ms between adjacent normal number of intervals (PNN50, 9.66%±5.40% vs. 6.98%±5.66%, t=-2.229, P=0.028) and heart rate variability triangle index (57.1±16.1 vs. 50.6±12.7, t=-2.271, P=0.025) were significantly higher. After acute exposure to high altitude, C-reactive protein (0.098±0.103 vs. 0.062±0.045 g/L, t=-2.132, P=0.037), aspartate aminotransferase (19.7±6.72 vs. 17.3±3.95 U/L, t=-2.231, P=0.028) and creatinine (85.1±12.9 vs. 77.7±11.2 mmol/L, t=-3.162, P=0.002) were significantly higher in the AMS group, while alkaline phosphatase (71.7±18.2 vs. 80.6±20.2 U/L, t=2.389, P=0.019), standard deviation of normal-to-normal RR intervals (126.5±35.9 vs. 143.3±36.4 ms, t=2.320, P=0.022), ejection time (276.9±50.8 vs. 313.8±48.9 ms, t=3.641, P=0.001) and heart rate variability triangle index (37.1±12.9 vs. 41.9±11.1, t=2.020, P=0.047) were significantly lower. Using the Lake Louise Score as the dependent variable, prediction equation were established to estimate AMS: Lake Louise Score=3.783+0.281×eosinophil-0.219×alkaline phosphatase+0.032×PNN50. Conclusions We elucidated the differences of physiological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level. We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.


Dynamic motor control is associated with treatment outcomes for children with cerebral palsy.
To estimate the impact of dynamic motor control on treatment outcomes in children with cerebral palsy. We used multiple regression on a retrospective cohort of 473 ambulatory children with cerebral palsy who underwent conservative treatment, single-level orthopaedic surgery, single-event multi-level orthopaedic surgery, or selective dorsal rhizotomy. Outcomes included gait pattern, gait speed, energy cost of walking, and the Pediatric Outcomes Data Collection Instrument. Explanatory variables considered were pre-treatment levels of each outcome, treatment group, prior treatment, age, and dynamic motor control computed from surface electromyography using synergy analysis. Effect sizes were estimated from the adjusted response. Pre-treatment levels had effect sizes 2 to 13 times larger than the next largest variable. Individuals with milder pre-treatment involvement had smaller gains or actual declines. Dynamic motor control was significant in all domains except energy cost. The effect size of dynamic motor control was second only to pre-treatment level, and was substantially larger than the effect size of treatment group for outcomes where both were significant (gait pattern 2:1, gait speed 4:1). The effect of dynamic motor control was independent of treatment group. Dynamic motor control is an important factor in treatment outcomes. Better dynamic motor control is associated with better outcomes, regardless of treatment.


APOL1 Risk Variants Associate With the Prevalence of Stroke in African American Current and Past Smokers.
African American smokers have 2.5 times higher risk for stroke compared with nonsmokers (higher than other races). About 50% of the African American population carry 1 or 2 genetic variants (G1 and G2; rare in other races) of the apolipoprotein L1 gene (APOL1). Studies showed these variants may be associated with stroke. However, the role of the APOL1 risk variants in tobacco-related stroke is unknown. In a cross-sectional study, we examined whether APOL1 risk variants modified the relationship between tobacco smoking and stroke prevalence in 513 African American adults recruited at University of California, San Francisco. Using DNA, plasma, and questionnaires we determined APOL1 variants, smoking status, and stroke prevalence. Using logistic regression models, we examined the association between smoking (ever versus never smokers) and stroke overall, and among carriers of APOL1 risk variants (1 or 2 risk alleles), and noncarriers, separately. Among participants, 41% were ever (current and past) smokers, 54% were carriers of the APOL1 risk variants, and 41 had a history of stroke. The association between smoking and stroke differed by APOL1 genotype (Pinteraction term=0.014). Among carriers, ever versus never smokers had odds ratio (OR) 2.46 (95% CI, 1.08-5.59) for stroke (P=0.034); OR 2.00 (95% CI, 0.81-4.96) among carriers of 1 risk allele, and OR 4.72 (95% CI, 0.62-36.02) for 2 risk alleles. Among noncarriers, smoking was not associated with a stroke. Current and past smokers who carry APOL1 G1 and/or G2 risk variants may be more susceptible to stroke among the African American population.


An ungrouped plant kinesin accumulates at the preprophase band in a cell cycle-dependent manner.
Past phylogenic studies have identified a plant-specific, ungrouped family of kinesins in which the motor domain does not group to one of the fourteen recognized families. Members of this family contain an N-terminal motor domain, a C-terminal armadillo repeat domain and a conserved destruction box (D-BOX) motif. This domain architecture is unique to plants and to a subset of protists. Further characterization of one representative member from Arabidopsis, Arabidopsis thaliana KINESIN ungrouped clade, gene A (AtKINUa), was completed to ascertain its functional role in plants. Fluorescence confocal microscopy revealed an accumulation of ATKINUA:GFP at the preprophase band (PPB) in a cell cycle-dependent manner in Arabidopsis epidermal cells and tobacco BY-2 cells. Fluorescence accumulation was highest during prophase and decreased after nuclear envelope breakdown. A conserved D-BOX motif was identified through alignment of AtKINU homologous sequences. Mutagenesis work with D-BOX revealed that conserved residues were necessary for the observed degradation pattern of ATKINUA:GFP, as well as the targeted accumulation at the PPB. Overall results suggest that AtKINUa is necessary for normal plant growth and/or development and is likely involved with PPB organization through microtubule association and specific cell cycle regulation. The D-BOX motif may function to bridge microtubule organization with changes that occur during progression through mitosis and may represent a novel regulatory motif in plant microtubule motor proteins.


Ultrastructural study on a severe infantile sialidosis (beta-galactosidase-alpha-neuraminidase deficiency).
This study was undertaken to elucidate ultrastructural changes in a severe infantile sialidosis. The materials examined in this study consisted of biopsied rectal mucosa and autopsied small intestine, liver and kidney. In the biopsy sample, axons contained a number of pleomorphic electron dense bodies, and numerous membrane-bound vacuoles were found in Schwann's cells, fibroblasts, endothelial cells, lymphocytes and plasma cells. In autopsy samples, neurons in Auerbach's myenteric plexus of the small intestine were filled with a number of membranous cytoplasmic bodies, pleomorphic dense bodies and vesicles containing dense materials. Hepatocytes in the liver, and glomerular and tubular epithelial cells in the kidney were also extended by a number of membrane-bound vacuoles. These ultrastructural changes in severe infantile sialidosis closely resemble those in GM1-gangliosidosis type 1.


Multiscale modelling of human hair.
We present a multiscale modelling approach to the mechanics of human hair fibres. On the microscale, a coiled coil of filament proteins was mechanically unfolded in a molecular-dynamics simulation. The force at unfolding was found to be ca. 1 nN, which we estimated to be an order of magnitude above the reversible force. Using the concept of folded/unfolded states, we developed a statistical mechanical model, which predicts a linear decrease of the yield stress with temperature. This was confirmed experimentally by stretching human hair fibres into the yield region at elevated temperatures. The role of correlation between unfolding units has been studied in more detail predicting an energy of ca. 12 kJ mol(-1) for the interface. The composite structure of hair at the nanometre scale was addressed using a particle-based model for a macrofibril. Mesoscale particles representing coiled coils of keratin proteins were assembled to filaments and embedded in a matrix of soft particles cross-linked to a network. The macrofibril was extended in a non-equilibrium computer simulation, while monitoring the tensile force. Thermal properties of the macrofibril in the yield region are in correspondence with the two-state model.