Unnatural causes of death and suicide among former adolescent psychiatric patients.
Compared with the general population, adolescent psychiatric patients are subject to premature death from all causes, but suicide-specific mortality rates in this population have not been carefully investigated. Therefore, we examined the high mortality due to unnatural causes, particularly suicide, using standardized mortality ratios (SMRs) relative to sex, diagnosis, and type of psychiatric service. A total of 3,029 patients aged 10-19 years presented to the outpatient clinic of a general hospital in Seoul, Korea, or were admitted to that hospital for psychiatric disorders from January 1995 to December 2006. Unnatural causes mortality risk and suicide mortality risk in these patients were compared with those in sex- and age-matched subjects from the general Korean population. The SMR for unnatural causes was 4.6, and for suicide it was 7.8. Female subjects, the young, and inpatients had the highest risks for unnatural causes of death or suicide. Among the different diagnostic groups, patients with psychotic disorders, affective disorders, and personality disorders had significantly increased SMRs for unnatural causes, and those with psychotic disorders, affective disorders, and disruptive behavioral disorders had significantly increased SMRs for suicide. The risks of unnatural death and suicide are high in adolescent psychiatric inpatients in Korea, but not as high in adolescent outpatients. Effective preventative measures are required to reduce suicide mortality in adolescent psychiatric patients, particularly female patients admitted for general psychiatric care.


Prevalence of trachoma in Yemen: results of population-based prevalence surveys of 42 evaluation units in nine governorates.
In suspected trachoma-endemic areas of Yemen, we sought to determine the prevalence of the sign trachomatous inflammation-follicular (TF) in children aged 1-9 years, and the potential individual and household risk factors for TF in that age group. We also sought to determine the prevalence of trichiasis in adults aged ≥15 years. We conducted a cluster-sampled survey in each of 42 evaluation units (EUs) comprising 166 rural districts of nine Governorates (Adh Dhale'a, Al Hodeihah, Al Jawf, Hadramoot, Hajjah, Ibb, Lahj, Ma'rib, Taiz) using the Global Trachoma Mapping Project systems and methodologies. Fieldwork was undertaken from September 2013 to March 2015. Risk factors for TF in children aged 1-9 years were evaluated using multilevel random effects logistic regression. The TF prevalence in children aged 1-9 years was ≥10% in two EUs (7 districts) and 5-9.9% in six EUs (24 districts). In adults aged ≥15 years, trichiasis prevalence was ≥0.2% in five EUs (19 districts). Being older (within the 1-9-year age bracket), being male, living in a household with higher numbers of children, and living in a household that reported the use of open defecation, were each independently associated with higher odds of TF. These surveys provided baseline data to enable planning for trachoma elimination. The World Health Organization Alliance for the Global Elimination of Trachoma by 2020 stands ready to assist Yemen once security considerations permit further surveys and implementation of control activities.


Development of a nurse-led chronic pain clinic in UK primary care.
We describe the development of an innovative, nurse-led chronic pain clinic in primary care. Benefit of the structured intervention was seen in terms of overall patient pain (as measured by the short form McGill-Melzack pain scale) with no overall impact on drug costs. A significant proportion (54%) of patients taking non-steroidal anti-inflammatory drugs were deemed to be at risk of gastropathy and in need of gastroprotection as defined by the clinic protocol. Areas worthy of further study are discussed.


Detection of ophthalmic artery occlusion by visual evoked potential during carotid-ophthalmic artery aneurysm clipping.
We report an intriguing case of carotid-ophthalmic artery (OA) aneurysm surgery, in which the visual evoked potential (VEP) wave diminished during temporary OA occlusion. VEP waves suddenly disappeared after clipping, and repositioning of the clip restored blood flow to the OA and recovered the VEP wave.


Integrated spatial health assessment of yellow perch (Perca flavescens) populations from the St. Lawrence River (QC, Canada), part B: cellular and transcriptomic effects.
Multi-biological level assessments have become great tools to evaluate the health of aquatic ecosystems. Using this approach, a complementary study was designed to evaluate the health of yellow perch (Perca flavescens) populations in the St. Lawrence River (Quebec, Canada). In the present study, stress responses were compared at the transcriptomic, cellular, and tissue levels in yellow perch collected at six sites along the river: Lake St. François, Lake St. Louis (north and south), Beauregard Island and Lake St. Pierre (north and south). These results complement the physiological and chemical parameters as well as pathogen infection investigated in a companion paper published in the present issue. Thiobarbituric acid reactive substance (TBARS) analyses indicated the presence of oxidative stress in fish collected in the southern part of Lake St. Louis and at the downstream sites of Lake St. Pierre. High lipid peroxidation levels were found in the muscle of yellow perch caught at Beauregard Island, located downstream of the Montreal's wastewater treatment plant, suggesting an impact of the municipal effluent on redox homeostasis. Transcriptomic results indicated the down-regulation of genes related to lipid, glucose, and retinoid in southern Lake St. Pierre as well as a decrease in retinoid storage. Overall, biochemical and molecular markers indicated that the health status of yellow perch followed a decreasing gradient from upstream to downstream of the St. Lawrence River. This gradient is representative of the cumulative negative impacts of human activities on water and habitat quality along the river.


Identification of a CE-SDS shoulder peak as disulfide-linked fragments from common CH2 cleavages in IgGs and IgG-like bispecific antibodies.
Fragmentation is a well-characterized degradation pathway of therapeutic antibodies and is usually monitored by capillary electrophoresis-sodium dodecyl sulfate (CE-SDS). Although fragments due to cleavage in CH2 domains linked by intrachain disulfide bonds are common and can be detected by reduced reversed-phase - liquid chromatography mass spectrometry (RP-LCMS) and reduced CE-SDS methods, their separation in nonreduced CE-SDS (nrCE-SDS) has not been reported but speculated as comigrating with intact IgG. A shoulder peak in nrCE-SDS was observed in the stability samples of an IgG-like bispecific antibody and was determined to be mainly caused by fragments from clipping at the C-terminus of leucine (L)306 or L309 (EU numbering) in the CH2 domain of both heavy chains (HCs) and, to a lesser degree, at the C-terminus of L182 in the CH1 domain of the knob HC. Subunit LCMS analysis verified that the crystallizable fragment contained variants with one or multiple mass additions of ~18 Da due to clipping. Further investigation revealed that CH2 clippings at L306 and L309 were largely due to proteolytic activity, and cleavages were present at various levels in all in-house IgG1 and IgG4 molecules studied. Our study shows that CH2 domain cleavages, with complementary fragments still linked by intrachain disulfide, can be electrophoretically resolved as a front shoulder of the main peak in nrCE-SDS. Given the high occurrence of CH2 cleavages in antibodies, these findings will have broad applicability and could help manufacturers of therapeutic antibodies in process improvement, product characterization, investigations, formulation stability, and stability comparability studies.


Genome-wide mapping of allele-specific protein-DNA interactions in human cells.
We describe a high-throughput method, named ChIP-SNP, for the identification of allele-specific protein-DNA interactions throughout the human genome. ChIP-SNP combines chromatin immunoprecipitation (ChIP) with whole-genome single nucleotide polymorphism (SNP) genotyping microarray analysis. We demonstrated that it can be used to accurately identify allele-specific binding of RNA polymerase II (RNAP) in the human fibroblast genome, uncovering imprinted genes and other allele-specific binding events. ChIP-SNP will facilitate the study of mechanisms of allele-specific gene expression.


The stabilizing axial spinal pillar in the lumbar spine.
A theoretical model of spinal stability is proposed. To present a biomechanical study in vitro using flexibility and loading tests of the normal lumbar spine and of two lumbar models of spinal stability in order to determine which of the lumbar middle-column model and the personal suggested model of lumbar central axial pillar is more resistant and stable. Hospital 'Sf.Treime', Iasi, Romania. Twenty-three fresh human cadaveric lumbar spines were tested with flexibility and loading tests of the intact lumbar functional units and of two types of spinal model specimens: 10 lumbar middle-column models and 13 lumbar central pillar model specimens. Parameters of vertebral motion and vertebral compression were compared to determine the differences between the types of spinal models. The flexibility tests show a significant increase in motion of the lumbar middle-column model specimens compared to the lumbar central pillar model specimens. The lumbar central pillar model specimens are three times more stable compared to the middle-column models. The compression tests show that the lumbar central axial pillar model specimens were more resistant, on average by 10% (30% maximum) compared to the other model. The lumbar model formed by the axial overlapping of the posterior half moon of vertebral body continued by the pedicles and the articular processes is more stable and more resistant compared to the middle-column model of the three-columns theory of Denis. In the lumbar spine this central axis spinal pillar is the structure of spinal stability and resistance, and I propose this central axial spinal pillar as the stabilizing structure for all the spine.


Delay Aversion in Attention Deficit/Hyperactivity Disorder: an empirical investigation of the broader phenotype.
Delay-related motivational processes are impaired in children with Attention Deficit/Hyperactivity Disorder (ADHD). Here we explore the impact of ADHD on the performance of three putative indices of Delay Aversion (DAv): (i) the choice for immediate over delayed reward; (ii) slower reaction times following delay; and (iii) increased delay-related frustration-to see whether these tap into a common DAv construct that differentiates ADHD cases from controls and shows evidence of familiality. Seventy seven male and female individuals (age range 6-17) with a research diagnosis combined type ADHD, 65 of their siblings unaffected by ADHD and 50 non-ADHD controls completed three delay tasks. As predicted the size of the correlation between tasks was small but a common latent component was apparent. Children with ADHD differed from controls on all tasks (d=.4-.7) and on an overall DAv index (d=.9): The battery as a whole demonstrated moderate sensitivity and specificity. In general, deficits were equally marked in childhood and adolescence and were independent of comorbid ODD. IQ moderated the effect on the MIDA. Scores on the DAv factor co-segregated within ADHD families. There is value in exploring the broader DAv phenotype in ADHD. The results illustrate the power of multivariate approaches to endophenotypes. By highlighting the significant, but limited, role of DAv in ADHD these results are consistent with recent accounts that emphasize neuropsychological heterogeneity.


Influence of the orientation of nest entrance, shading, and substrate on sampling trap-nesting bees and wasps.
The use of trap nests supplies important biological information concerning the biology of bees and wasps. However, the knowledge about the factors that influence the management of these groups is still scarce. Our study aimed to analyze the effects of the orientation of nest entrance, shading, and block material (wood or vermiculite) on the frequency, richness, and composition of trap-nesting species at two agricultural areas in the Atlantic Forest region of the state of Paraiba. Both sites showed similar species richness and composition. However, a higher number of nests was found at the Alhandra site, mainly of the species Trypoxylon aurifrons Shuckard and Centris analis (F.). Regarding the orientation, the number of nest entrances oriented to prevailing wind direction was significantly smaller. Most species nested more frequently in shaded areas than in sunny areas and the wood blocks were more attractive than the vermiculite blocks, especially for bees.


CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity.
CD26 is a multifunctional cell surface glycoprotein expressed by T and B cells. It exhibits a dipeptidyl-peptidase activity (DPP-IV) that cleaves the penultimate proline from the N-terminus of polypeptides, thereby regulating their activity and concentration. Using CD26-/- mice resulting from targeted inactivation of the gene, we examined the consequences of a DPP-IV defect on behavioural response to nociceptive stimuli and concentration of the pain modulator peptides substance P (SP) and endomorphin 2, two DPP-IV substrates. CD26 inactivation induced a three-fold decrease in circulating endopeptidase activity while that found in brain extracts was normal, albeit very weak. CD26-/- mice had high SP concentrations in plasma (3.4+/-1 pg/ml versus 1.5+/-0.3 pg/ml, P<10(-3)) but not in brain extracts (35+/-12 pg/ml versus 32+/-9 pg/ml, P>0.05). Endomorphin-2 levels in the two groups were in the same range for plasma and brain extracts. CD26-/- mice displayed short latencies to nociceptive stimuli (hot plate test: 6.6+/-1.2 s versus 8.6+/-1.5 s, P<10(-4); tail pinch test: 3.1+/-0.6 s versus 4.2+/-0.8 s, P<10(-3)). Administration of an SP (NK1) receptor antagonist or DPP-IV to CD26-/- mice normalised latencies. DPP-IV inhibitors decreased latencies only in CD26+/+ mice. Our observations represent the first fundamental evidence showing that DPP-IV influences pain perception via modulation of the peripheral SP concentration. Our work also highlights the role of peripheral NK1 receptors in nociception.


Comparative studies on the absorption and fluorescence responses of hemicyanine to HSO3-, CN-, HS- and ClO.
A fluorescent probe Hcy-Im bearing an indolium-hemicyanine structure was designed and synthesized to compare its responses to four anions, namely HSO3-, CN-, HS- and ClO-. The results disclosed that Hcy-Im reacted with all these four anions in 5% DMSO-PBS buffer with different speeds and spectral changes. Hcy-Im responded to HSO3- markedly quicker than CN- and HS-, and it responded to CN- a little quicker than HS- while the response to ClO- was much slower than the other three anions. The detection limits for these four anions were calculated to be 0.15 μM, 1.32 μM, 2.07 μM and 2.29 μM, respectively. The characteristic conjugated CN+ and CC bonds in Hcy-Im were responsible for the responses towards these four anions via a Michael addition-rearrangement reaction, a 1, 2-addition reaction or an oxidation reaction. These different sensing mechanisms were verified by 1HNMR and HRMS. Thus, it could be inferred that hemicyanine-based fluorescent probe could detect HSO3- sensitively and selectively while the interference of HSO3- should not be neglected when it was used for the detection of CN-, HS- and ClO-. Moreover, as HSO3-, HS- and ClO- are anions endogenously generated in human bodies, enough attention should be paid to the presence of physiological level of these three anions in certain tissues when hemicyanine-based fluorescent probe is applied for the detection of biorelevant analytes in biological samples.


[Operative therapy of fractures of the distal femur. Predictive factors for a complicated course].
Fractures of the distal femur are rare injuries that are mainly treated operatively. Complication rates remain high. This study aimed to analyse complications following the operative treatment of these fractures and to identify predictive factors that have the potential to identify patients who are at risk for a complicated course of treatment. We retrospectively analysed all fractures of the distal femur that were treated operatively at our institution between 2005 and 2015. Besides patient and fracture-specific data, surgical details and the types of complications that occurred were recorded and analysed. Open soft tissue damage, the polytraumatised patient and the timing of surgery (i.e. emergency surgery) are significant risk factors for the development of a nonunion. A risk factor that predicts a postoperative infection is open soft tissue damage. Type C fractures, stabilisation as emergency surgery and an accompanying polytrauma are risk factors for a postoperative pneumonia. The complication rate is significantly determined by surgical factors. To reduce the rate of nonunion, infection and pneumonia, the optimisation of the patient's general condition before surgery and optimal surgical care is more important than an immediate emergency surgery.


Migration and distribution characteristics of organic and inorganic fractions in condensable particulate matter emitted from an ultralow emission coal-fired power plant.
Condensable particulate matter (CPM) is the main part of total particulate matter (TPM) discharged from coal-fired power plants. In this study, a new analytical method was proposed for accurately quantifying the organic components including n-alkanes and phthalates in CPM that sampled from an ultralow emission coal-fired plant by using the Gas Chromatography-Mass Spectrometer (GC-MS) and the mixed standard solution. The organic fraction made up 53.13%, 50.90%, 52.44% of the CPM tested at the outlet of the low-low temperature electrostatic precipitator (LLT-ESP), the wet flue gas desulfurization (WFGD) and the wet electrostatic precipitator (WESP), respectively. The total concentration of 19 kinds of n-alkanes range from 0.328 mg/Nm3 to 0.854mg/Nm3 with C24-C30 becoming the major n-alkanes compounds in all sampling sites. The chief component of the tested phthalate was the di-n-butyl ortho-phthalate (DBP) which comprised 95.43%, 88.29%, 95.33% of the total of five kinds of phthalates. The WFGD contributed to the reduction of phthalates and the generation of n-alkanes while the effects on WESP were opposite. Furthermore, the existing air pollution control devices (APCDs) had no significant selection for the removal of n-alkanes causing the proportions of different n-alkanes were almost the same in different sampling sites. Also, the mechanism of the APCDs on the removal of CPM organic fraction was proposed primarily. The proportion of organic components measured in the organic fractions was less than 15%. Accurate quantification of other organic compounds and the mechanism of pollutant removal should be studied in the future.


Chronic neurological disorders and related comorbidities: Role of age-associated physiological changes.
Current knowledge indicates that the physiological aging process starts with subclinical changes at the molecular and cellular level, which affect nearly all physiological systems. For example, the age-associated remodeling of the immune system (i.e., immunosenescence) and vascular aging per se can contribute to frailty and vulnerability among older adults. They are also described as being implicated in the pathophysiology of some major chronic comorbid conditions such as age-associated diseases of the central (e.g., stroke, Parkinson's disease, Alzheimer's disease, and related disorders) and peripheral (e.g., polyneuropathy) nervous systems. These neurologic disorders are also among the greatest contributors to geriatric syndromes, which refer to highly prevalent and chronic conditions among aged people of multifactorial origin, such as delirium, falls, incontinence, and frailty. Neurologic disorders can also occur in patients with one or more geriatric syndromes and thus further interfere with the quality of life, physical function, morbidity, and mortality. This chapter presents and discusses in three sections the complex interrelationships between the main determinants of aging with a specific focus on vascular aging, chronic neurologic disorders, and the specific clinical presentation of geriatric syndromes in older people.


Leucine catabolism and incorporation into tissue proteins in thyroparathyroidectomized rats.
We investigated parameters of leucine metabolism in thyroparathyroidectomized (TPX) and pair-fed control rats using a technique of continuous infusion of [l-14C]leucine. The rate of leucine turnover was significantly smaller in TPX than in control rats (42.5 +/- 2.6 vs 35.1 +/- 1.9 mumole/hr/100 g, mean +/- SEM, six rats). There was no significant difference between rates of alpha-decarboxylation of leucine by the two groups of rats. The protein incorporation of leucine was significantly smaller in the muscle of TPX than control rats (39 +/- 5 vs 24 +/- 4 pmole/mg protein, mean +/- SEM, six rats) but in liver it was not significantly different. Thyroparathyroidectomy also had no significant effect on concentration of either leucine or its ketoacid (alpha-ketoisocaproate) in plasma, liver, and muscle. We conclude that hypothyroidism does not alter catabolism of leucine but reduces its incorporation into muscle protein.


Cocarcinogens of the diterpene ester type from Croton flavens L. and esophageal cancer in Curaçao.
From the roots of Croton flavens L., 3 highly irritant and tumor promoting Croton factors F1--F3 and the corresponding 3 cryptic Croton factors F'1--F'3 were isolated and characterized as novel esters of 16-hydroxy- and 4-deoxy-16-hydroxyphorbol, respectively. These findings suggest that tumor promoters of the phorbol ester type, ingested through the widespread and frequent use of Croton flavens according to local habits, may be causally related to the well recognized high rate of esophageal cancer on Curaçao.


In search of novel water soluble forskolin analogues for positive inotropic activity.
Using the novel lead from hydroxy acetyl substituted forskolin analogues, such as 7 beta-hydroxyacetyl-7 beta-deacetyl forskolin or 6 beta-hydroxyacetyl forskolin, a number of water soluble omega-amino acyl derivatives were synthesized. Two such compounds 6 and 18 showed better in vitro activity but failed to show in vivo activity.


El Niño Southern Oscillation (ENSO) effects on local weather, arboviral diseases, and dynamics of managed and unmanaged populations of Aedes aegypti (Diptera: Culicidae) in Puerto Rico.
We investigated the effects of interannual El Niño Southern Oscillation (ENSO) events on local weather, Aedes aegypti populations, and combined cases of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses in 2 communities with mass mosquito trapping and 2 communities without mosquito control in southern Puerto Rico (2013-2019). Gravid adult Ae. aegypti populations were monitored weekly using Autocidal Gravid Ovitraps (AGO traps). Managing Ae. aegypti populations was done using 3 AGO traps per home in most homes. There were drought conditions in 2014-2015 concurrent with the emergence of a strong El Niño (2014-2016), wetter conditions during La Niña (2016-2018), a major hurricane (2017), and a weaker El Niño (2018-2019). The main factor explaining differences in Ae. aegypti abundance across sites was mass trapping. Populations of Ae. aegypti reached maximum seasonal values during the wetter and warmer months of the year when arbovirus epidemics occurred. El Niño was significantly associated with severe droughts that did not impact the populations of Ae. aegypti. Arbovirus cases at the municipality level were positively correlated with lagged values (5-12 mo.) of the Oceanic El Niño Index (ONI), droughts, and abundance of Ae. aegypti. The onset of strong El Niño conditions in Puerto Rico may be useful as an early warning signal for arboviral epidemics in areas where the abundance of Ae. aegypti exceeds the mosquito density threshold value.


Exercise: the data on its role in health, mental health, disease prevention, and productivity.
How would you define exercise? If you look up exercise in the dictionary, it is defined as physical activity used for the purpose of conditioning any part of the body. Exercise is an important topic because in the United States less than 50% of the total population exercises on a regular basis. The lack of regular physical activity is linked to an increased rate of obesity, development of chronic diseases, and an overall decline in health. This article uses an evidence-based approach to demonstrate how exercise affects health, mental health, disease prevention, and productivity.


Improving outcome in meningococcal disease: don't forget compartment syndrome!
To advocate a surgical intervention that can prevent the loss of limbs in patients with meningococcal disease. Case report. Pediatric intensive care unit. A 4-month-old male infant presenting with acute circulatory failure due to meningococcal disease. Measurements of compartment pressures of all extremities and echo-Doppler of peripheral arteries were performed at regular intervals, starting at admittance to the pediatric intensive care unit. After compartment syndrome in the lower extremities was diagnosed, emergency surgical intervention (fasciotomy and arteriolysis) was performed in the intensive care unit. During surgery, the compartments initially revealed pale, poorly perfused tissue. After decompression, immediate bulging of the muscles and restoration of microcirculation were seen. All digits were spared, and muscle compartments remained vital with exception of the tibialis anterior and extensor hallucis longus muscles in the left leg. Several ecchymoses and purpura of the lower extremities caused skin necrosis, necessitating skin transplants. No other surgical intervention was required. In meningococcal disease, compartment syndrome can occur within hours after initial presentation due to massive capillary leakage and circulatory failure. Immediate surgical intervention is the gold standard in treatment, making early recognition vital. In all patients presenting with meningococcal disease, compartment syndrome should be considered and early monitoring included in the initial evaluation.


Pigmented central neurocytoma.
Central neurocytoma is a low-grade neuronal neoplasm that occurs most often within the lateral ventricles. We report the case of a 60-year-old woman who presented with gait problems, headache and memory loss. Preoperative evaluation demonstrated a heterogeneous, hypervascular and partially cystic mass in the left lateral ventricle. Histopathological examination revealed characteristic features of central neurocytoma, including immunoreactivity for synaptophysin, as well as the unusual feature of abundant pigment in the cytoplasm of tumor cells. Special stains revealed iron, consistent with hemosiderin, but found no evidence of melanin or melanosomes. Previous reports of pigmented central neurocytoma have described the presence of lipofuscin or neuromelanin. To our knowledge, the present case represents the first example of pigmented central neurocytoma secondary to hemosiderin deposition.


Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.
Whereas regular exercise is associated with lower risk of cardiovascular disease and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans. Cardiopulmonary exercise testing and metabolite profiling was performed on Framingham Heart Study participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411). We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate. Changes included reductions in metabolites implicated in insulin resistance (glutamate, -29%; P=1.5×10-55; dimethylguanidino valeric acid [DMGV], -18%; P=5.8×10-18) and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%; P=6.1×10-67), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%; P=2.8×10-169), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%; P=7.4×10-38), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate Framingham Heart Study replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% false discovery rate. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index. There was attenuation of favorable excursions in some metabolites in individuals with higher body mass index and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct preexercise metabolite levels were associated with different physiologic dimensions of fitness (eg, ventilatory efficiency, exercise blood pressure, peak Vo2). We identified 4 metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), 2 of which were associated with overall mortality over median follow-up of 23.1 years (P≤0.003 for both). In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, cardiovascular disease, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study.


Flipping a Single Lecture in a Survey Course to Active Learning: Do the Benefits Justify the Costs?
Health education has seen a surge of interest in active learning strategies like the flipped classroom. In response to the need for physical distancing in the age of COVID-19, schools are rapidly shifting to web-based and video technology, sometimes without being able to predict the outcomes of this change. The objectives of this pilot experiment were to (1) compare active learning (AL) methods versus traditional lecture for transmitting and retaining knowledge in the introductory pre-clinical medical school curriculum and (2) weigh whether the costs required to flip instruction were justified by learning gains. The authors took a 2 h lecture for first-year medical students and converted half of it into an AL format. In-person lecture and active learning groups were compared in terms of student knowledge at pre-intervention, immediately post-intervention, and 6 months post-intervention. Costs for first-time delivery and anticipated costs for repeat delivery of each format were calculated. Students' gains in knowledge increased in both groups, though more by lecture (control) than via AL. Delivering a single hour of new AL costs 3.4 times that of a new lecture. Repeat offerings of the AL intervention were estimated to cost 5.4 times that of the repeat lecture. The 1 h AL session was less effective than the 1 h lecture for knowledge acquisition and retention at 6-month follow-up. The AL was more expensive to produce and to repeat. Future research needs to evaluate the impact of AL with a larger N, control group, structured faculty/resident procedures, and assessment of gaining and applying attitudes and skills in addition to knowledge.


[The role of the blood viscosity and hematocrit value in acute stroke. Experimental considerations].
The link between blood viscosity, Ht and the onset of stroke is highlighted and reports in the literature are examined. On this basic, the paper proposes an experimental model of cerebral ischaemia in the rabbit as providing a better insight into this aspect which may be highly significant, particularly in the prevention of strokes.


[Classification of results of studying blood plasma with laser correlation spectroscopy based on semiotics of preclinical and clinical states].
The usage of laser correlation spectroscopy for verification of preclinical and clinical states is substantiated. Developed "semiotic" classifier for solving the problems of preclinical and clinical states is presented. The substantiation of biological algorithms as well as the mathematical support and software for the proposed classifier for the data of laser correlation spectroscopy of blood plasma are presented.


Mechanism for transport of ivermectin to the stratum corneum in rats.
Ivermectin (IVM) is used as an oral medication for scabies, a skin infection caused by a mite, sarcoptes scabiei, which parasitizes in the stratum corneum. After oral administration IVM is absorbed from the intestine, and finally distributed to the stratum corneum to eliminate the mites. However its transport mechanism remains unclear. A pharmacokinetic study was performed using hairless Wistar Yagi (HWY) rats, which have no or atrophied sebaceous glands, and Wistar rats as a reference. After oral administration of IVM to both groups, the area under the concentration-time curve of IVM in the dermis and epidermis (dermis-epidermis) of HWY rats were about 60% lower than that of Wistar rats, even though the plasma concentration profiles were comparable in both groups. In addition at 12 h after the administration, IVM concentration in the outer stratum corneum, the shallower layer of the dermis-epidermis, was higher compared to that in the deeper layer. In the dermis-epidermis of the skin from various locations, the concentrations of IVM and squalene, the latter of which is secreted to the skin surface via the sebaceous gland, were positively well correlated. Those results suggest that IVM is transported to the stratum corneum via the sebaceous glands.


Effect of dust load on the leaf attributes of the tree species growing along the roadside.
Dust is considered as one of the most widespread air pollutants. The objective of the study was to analyse the effect of dust load (DL) on the leaf attributes of the four tree species planted along the roadside at a low pollution Banaras Hindu University (BHU) campus and a highly polluted industrial area (Chunar, Mirzapur) of India. The studied leaf attributes were: leaf area, specific leaf area (SLA), relative water content (RWC), leaf nitrogen content (LNC), leaf phosphorus content (LPC), chlorophyll content (Chl), maximum stomatal conductance (Gs(max)), maximum photosynthetic rate (A (max)) and intrinsic water-use efficiency (WUEi). Results showed significant effect of sites and species for DL and the leaf attributes. Average DL across the four tree species was greater at Chunar, whereas, the average values of leaf attributes were greater at the BHU campus. Maximum DL was observed for Tectona grandis at Chunar site and minimum for Syzygium cumini at BHU campus. Across the two sites, maximum value of SLA, Chl and Gs(max) were exhibited by S. cumini, whereas, the greatest value of RWC, LNC, LPC, A (max) and WUEi were observed in Anthocephalus cadamba. A. cadamba and S. cumini exhibited 28 and 27 times more dust accumulation, respectively, at the most polluted Chunar site as compared to the BHU campus. They also exhibited less reduction in A (max) due to dust deposition as compared to the other two species. Therefore, both these species may be promoted for plantation along the roadside of the sites having greater dust deposition.


The influence of hydration on the conformation of bovine serum albumin studied by solid-state 13C-NMR spectroscopy.
13C proton-decoupled cross-polarization magic-angle spinning nmr spectra of bovine serum albumin are reported as a function of hydration. Increases in hydration level enhance the resolution of the peak centered at about 40 ppm but has little or no effect on the other spectral peaks. Hydration has little effect on either the rotating frame proton spin-lattice relaxation time or the cross-relaxation time for any of the peaks, suggesting that the efficiency of dipolar coupling is largely preserved on hydration of the protein. Resolution enhancement of the peak at 40 ppm is not understood, but possible sources of the behavior include a decrease in the line width of contributing resonances from lysine epsilon carbons due to increased motional averaging on hydration, reordering of disulfide bridges, and titration shifts induced by hydration. Hydration of bovine serum albumin appears to have little effect on the distribution of conformations sampled by the protein so that the broad distribution of conformations observed in the dry state is also observed in the fully hydrated state. This is in contrast to lysozyme where significant ordering of the conformation is seen on hydration.


The thoracic windows for electrical ventricular defibrillation current.
The thoraces of dogs were mapped out to identify those areas where defibrillating current gains easiest access to the heart. Of all of the transchest and chest-to-back electrode locations, the lowest current dose (0.6 amp. per kilogram of body weight) was found with one electrode over the apex-beat area with transchest electrodes and slightly anterior to the apex-beat area with chest-to-back electrodes.


Potential possibilities of using phage typing in elimination of multidrug resistant staphylococci.
Coagulase-negative staphylococci (CoNS) have become the most often isolated bacteria from blood culture, spinal fluid and respiratory tracts of neonates. These nosocomial strains are often resistant to oxacillin and other antibiotics (macrolides, aminoglycosides and fluorochinolones). 50 multidrug resistant CoNS strains isolated from bloodstream neonatal infections were tested for sensitivity to 23 lytic staphylococcus bacteriophages. No lytic patterns for 19 of the phages were observed. Phages P4, A3R and 676/Z were active against 46%, 54% and 56% of the strains, respectively. In general, 60% of CoNS isolates were susceptible to one or more of the staphylococcus bacteriophages.


Bayesian estimation on diagnostic performance of Face, Legs, Activity, Cry, and Consolability and Neonatal Infant Pain Scale for infant pain assessment in the absence of a gold standard.
Nonverbal pediatric patients such as infants are unable to describe their pain, which leads to the lack of a gold standard scale for their pain assessment. The aim of this study was to estimate the diagnostic performance of Face, Legs, Activity, Cry, and Consolability (FLACC) scale and Neonatal Infant Pain Scale (NIPS) for infants' pain in the absence of a gold standard. This prospective observational study recruited 202 postoperative infants, aged <12 months. Postoperative pain intensity was evaluated using FLACC and NIPS scales. The diagnostic performance of these two scales was to estimate using a Bayesian latent class model with conditional dependence. McNemar's test was applied to test whether NIPS and FLACC tests differ from each other. Under a combined model with conditional dependence, the median posterior sensitivity and specificity of the FLACC were 89.94% (95% CI: 78.48-96.83%) and 87.82% (95% CI: 78.6-95.23%), respectively. The sensitivity and specificity of the NIPS were 85.94% (95% CI: 72.15-95.6%) and 92.61% (84.05-97.52%), respectively. McNemar's test demonstrated no significant difference between FLACC and NIPS in either sensitivity or specificity. Both the FLACC and NIPS have excellent sensitivity and specificity for pain assessment in infants. The comparison test showed that the FLACC scale was no different to the NIPS scale in sensitivity and specificity.


Crystallographic analysis of RsmA, a ribosomal RNA small subunit methyltransferase A from Staphylococcus aureus. Corrigendum.
The paper by Liu et al. [(2015), Acta Cryst. F71, 1063-1066] is corrected.


Tuberculosis diagnosis using immunodominant, secreted antigens of Mycobacterium tuberculosis.
Tuberculosis (TB) remains a major public health concern in most low-income countries. Hence, rapid and sensitive TB diagnostics play an important role in detecting and preventing the disease. In addition to established diagnostic methods, several new approaches have been reported. Some techniques are simple but time-consuming, while others require complex instrumentation. One prominent and readily available approach is to detect proteins that Mycobacterium tuberculosis secretes, such as Mpt64, the 6-kDa early secreted antigenic target (Esat6), the 10-kDa culture filtrate protein (Cfp10), and the antigen 85 (Ag85) complex. Although their functions are not fully understood, a growing body of molecular evidence implicates them in M. tuberculosis virulence. Currently these biomarkers are either being used or investigated for use in skin patch tests, biosensor analyses, and immunochromatographic, immunohistochemical, polymerase chain reaction-based, and enzyme-linked immunosorbent assays. This review provides a comprehensive discussion of the roles these immunodominant antigens play in M. tuberculosis pathogenesis and compares diagnostic methods based on the detection of these proteins with more established tests for TB.


Wave-like patterns in parameter space interpreted as evidence for macroscopic effects resulting from quantum or quantum-like processes in the brain.
Data from eight numerosity estimation experiments reliably exhibit wave-like patterns in plots of the standard deviations of the response times along the abstract parameter of the magnitude of the error in the numerosity estimation. An explanation for this phenomenon is proposed in terms of an analogy between response times and error magnitude on one hand, and energy and position of quantum particles on the other, constructed using an argument for an overlap between the mathematical apparatus describing Hopfield-type neural networks and quantum systems, established by some researchers. Alternative explanations are presented within the traditional explanatory framework of oscillations due to neural firing, involving hypothetical mechanisms for converting oscillation patterns in time to oscillation patterns in the space of an abstract parameter, such as the magnitude of the error during numerosity estimation. The viability of the proposal of causal influences propagating from the microscale of quantum phenomena to the macroscale of human behavior, needed for the first type of explanation, is exemplified by the phenomenon of magnetoreception in some species of birds, which is allegedly quantum in nature.


The place of solar power: an economic analysis of concentrated and distributed solar power.
This paper examines the cost and benefits, both financial and environmental, of two leading forms of solar power generation, grid-tied photovoltaic cells and Dish Stirling Systems, using conventional carbon-based fuel as a benchmark. First we define how these solar technologies will be implemented and why. Then we delineate a model city and its characteristics, which will be used to test the two methods of solar-powered electric distribution. Then we set the constraining assumptions for each technology, which serve as parameters for our calculations. Finally, we calculate the present value of the total cost of conventional energy needed to power our model city and use this as a benchmark when analyzing both solar models' benefits and costs. The preeminent form of distributed electricity generation, grid-tied photovoltaic cells under net-metering, allow individual homeowners a degree of electric self-sufficiency while often turning a profit. However, substantial subsidies are required to make the investment sensible. Meanwhile, large dish Stirling engine installations have a significantly higher potential rate of return, but face a number of pragmatic limitations. This paper concludes that both technologies are a sensible investment for consumers, but given that the dish Stirling consumer receives 6.37 dollars per watt while the home photovoltaic system consumer receives between 0.9 and 1.70 dollars per watt, the former appears to be a superior option. Despite the large investment, this paper deduces that it is far more feasible to get few strong investors to develop a solar farm of this magnitude, than to get 150,000 households to install photovoltaic arrays in their roofs. Potential implications of the solar farm construction include an environmental impact given the size of land require for this endeavour. However, the positive aspects, which include a large CO2 emission reduction aggregated over the lifespan of the farm, outweigh any minor concerns or potential externalities.


Electrically-induced mechanical activity of the isolated guinea-pig sciatic nerve. Influences of calcium and anoxia.
The electrically-induced motility of isolated segments of guinea-pig sciatic nerves is reported. This motility was characterized by waves of tensional variations. The removal of Ca2+ from the suspending solution, the addition of EDTA as well as anoxia, resulted in a decrement of tension accompanied by a prolonged duration of the cycles of mechanical activity.


Defects in the prostaglandin-system--heredity, prevalence and vascular risk analysis.
2180 healthy adults, 620 patients (90% with cardiovascular disease, 10% others), 143 newborns and 351 relatives of persons in whom any abnormality of the prostaglandin (PG)-system had been discovered were involved in the Viennese Initiative for Prostaglandin (VIP)-Screening from 1984 through May 1989. The defects discovered were either inborn or acquired ones and were either familial or non-familial. The highest number of defects (54.8% of the total) identified were associated with PGI2. They indicated a lack of the PGI2-synthesis stimulating plasma factor (PF)-activity (n = 17) and PGI2-stabilizing capacity in plasma (defect 'Vienna-Döbling', n = 4, 12.9% of total), absence of high-affinity PGI2-binding sites on platelet membranes and lack of response of platelets to PGI2 (defect 'Vienna-Hietzing', n = 2, 6.5% of total). Furthermore, a lack of cyclooxygenase (n = 2, 6.5% of total), 12-lipoxygenase (defect 'Vienna-Penzing', n = 3, 9.7% of total) and thromboxane synthetase (n = 3, 9.7% of total) activities were diagnosed. In newborn screening, the PF-absence amounted to 2.8% (4/143), the lack of PGI2-stabilizing capacity to 0.7% (1/143). In adults, the prevalence is difficult to assess. Nevertheless, our findings indicate a frequency of 0.93% (26/2800) of defects in the PG-system among the adult Viennese population. The lack of PF-activity seems to be by far the most frequent one (0.46%, 13/2800). Other defects are much less common. It is not clear whether the incidence in healthy subjects or in patients with cardiovascular disease is different from each other. Further, it remains to be assessed whether there is a causative relation to vascular events or just an association. More intensive screening activities should validate the diagnostic, pathogenetic and therapeutic impact of the various defects in the PG-system.


Characterization of area radioactive contamination of near-surface soil at the Sary-Uzen site in the Semipalatinsk test site.
The paper provides study of the radioactive contamination of near-surface soil at the Sary-Uzen site in the Semipalatinsk test site (STS). Increased values of natural radionuclides in the studied area were not detected, which indicates the absence of possible geochemical anomalies that could create an elevated radiation background. Radioactive contamination by technogenic radionuclides is caused by two factors. The first factor is fallout of radioisotopes from the atmosphere because of an explosion on September 24, 1951 at the "Experimental field" site. The fallout plume extended from the north-western part of the site to the very south. The range of activity concentration values for 241Am in soil varies from <0.3 Bq/kg to 390 Bq/kg, with an average value of 5 Bq/kg; for 137Cs from <1.1 Bq/kg to 330 Bq/kg, with an average value of 55 Bq/kg. A second, but more significant factor is the fallout of radioisotopes due to underground nuclear tests with radioactive release that took place in boreholes on the site itself. The largest area of contamination (about 8 km) is the fallout from testing borehole No. 101 (241Am to 920 Bq/kg and 137Cs to 12150 Bq/kg).


The association of obesity with cardiovascular events in patients with peripheral artery disease.
This systematic review aimed to summarise published evidence that has assessed the association of obesity with major cardiovascular events (CVEs) (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death) in patients with peripheral artery disease (PAD). Studies investigating the association of markers of obesity with CVEs were identified by searching the PUBMED database. To be eligible for inclusion studies had to report an established measure of adiposity, i.e. body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) or an imaging technique to quantify adipose distribution. A total of 9319 patients with PAD were followed for a mean of 1.0-5.7 years in the 7 studies identified. Four studies assessed BMI; one study assessed BMI and WC; one study assessed BMI, WC and WHR; one study assessed WHR. Both of the studies which assessed multiple adipose measures reported a more powerful positive association of WC with CVEs than BMI; one study reported less CVEs in obese subjects as defined by BMI; one study reported a negative association of overweight but not obesity, defined by BMI, with CVEs; one study reported an inverse association of BMI >20 with CVEs; one study did not find a significant association between WHR and cardiovascular death; one study did not find a significant association between BMI and CVEs. Meta-analysis of reported risk ratios found a mild positive association between combined measures of obesity and CVEs in patients with PAD (RR 1.09; 95%CI 1.03-1.16, P = 0.006; random effects model). This meta-analysis suggests that obesity is an independent risk factor for CVEs in patients with PAD however larger and more homogeneous studies using equivalent anthropometric measures are needed for more definitive evidence.


[Nutrition in dementia].
Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. In an international expert group, initiated by the European Society for Clinical Nutrition and Metabolism (ESPEN), 26 evidence-based recommendations for nutritional care of older persons with dementia have been developed, covering the topics of screening and assessment of malnutrition, strategies to support oral nutrition, oral supplementation and artificial nutrition. This article is a short version of the guideline.


Genetic susceptibility, predicting risk and preventing cancer.
A polygenic approach to disease prevention has become a realistic goal that has arisen from the sequencing of the human genome. Some believe it will be possible to identify individuals as susceptible by their genotype and to prevent disease by targeting interventions to those at risk. However, doubts have been expressed about the magnitude of these genetic effects, and hence the potential to apply them either to individuals or to populations. Published data suggest that the familial aggregation of breast cancer not due to the known high penetrance genes is polygenic, which implies that the distribution of risk in the population is continuous. This model is likely to apply to other common cancers. The utility of a continuous distribution for identifying a high-risk group of the population for targeted preventive intervention depends on the spread of that risk distribution. For breast cancer, the data are compatible with a log-normal distribution of genetic risk in the population which is sufficiently wide to provide useful discrimination of high- and low-risk groups. Assuming all the susceptibility genes could be identified, the half of the population at highest risk would account for 88% of all cases. In contrast, if currently identified risk factors for breast cancer were used to stratify the population, the half of the population at highest risk would account for only 62% of all cases. These results suggest that in the future the construction and use of genetic risk profiles may provide significant improvements in the efficacy of population-based programmes of intervention for cancers and other diseases.


Therapeutic approaches to achieve desired blood pressure goals: focus on calcium channel blockers.
The new guidelines for blood pressure control recommended by the World Health Organisation, the International Society of Hypertension, and the JNC VI require that blood pressure be lowered to levels of < 130/85 mmHg in persons with either diabetes or renal insufficiency. A review of over 20 clinical trials performed over the last two decades indicates that an average of 62% of the participants required more than two medications to achieve a goal of < 140/90 mmHg. Thus, with the new guidelines it is clear that an even higher proportion of people will require at least two different medications to achieve this lower goal. Certain classes of antihypertensive medications are relatively more efficacious for lowering blood pressure in certain ethnic and racial groups, thus reducing the probability that two or more agents will be needed to achieve a stated blood pressure goal. This is exemplified by the effects of calcium channel blockers in African-Americans. However, even in these groups many require at least two different antihypertensive agents to achieve the blood pressure goal. The fixed-dose combinations of a calcium channel blocker and ACE inhibitor offer the advantages of complementary physiologic action, improved tolerability, lower side-effect profile, enhanced salutary effects on target organs, better compliance, and lower cost. Varieties of fixed-dose combination regimens for blood pressure lowering are available for clinical use. This article focuses on the subclasses of calcium channel blockers and their role in altering the natural history of both cardiovascular and renal disease. The article further discusses the role of fixed-dose agents with regard to their place in the antihypertensive armamentarium.


Differential effectiveness of EMG-feedback versus combined EMG-feedback and relaxation instructions in the treatment of tension headache.
After a 2 1/2 week baseline period 18 muscle tension headache patients were randomly assigned to one of three conditions: waiting list, formal EMG-feedback training, combined training of EMG-feedback and progressive relaxation. Patients in the two treatment conditions obtained 12 training sessions and returned 3 months after treatment for a follow-up session. Both treatment conditions were equivalent in their effect on EMG of m. frontalis and on headache scores, against stability for waiting list patients as observed in a separate analysis. Changes over treatment in both parameters were significantly correlated. Among changes in headache subparameters, the only significant correlation with changes in frontalis EMG was found for duration of pain. In both treatment conditions a generalizing effect to neck muscles was observed. Among personality variables decreases were found in neuroticism and somatization at follow-up for the combined training conditions, whereas the EMG-feedback alone condition remained unaltered. The combined training condition also proved superior in reducing operant pain behavior.


Assessment of safety of non-anesthesiologist-assisted endoscopic retrograde cholangiopancreatography based on performance status in elderly patients.
Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly performed in the elderly patients, yet little is known concerning objective criteria of safety. This study aimed to determine the potential predictors for the procedure-related outcomes. Two hundred eighty-one patients older than 70 years who were indicated for ERCP (group A [n = 195], 70-79 years of age; group B [n = 86], ≥ 80 years of age) were prospectively enrolled and analyzed for the development of serious adverse events related to ERCP. ERCP was not performed in six patients at high risk for the procedure. There were significant differences between group A and B in Duke Activity Status Index (DASI) (23.1 vs 14.9, P < 0.01) and Eastern Cooperative Oncology Group performance status (3 and 4, 49/195 vs 33/86, P < 0.05). Major ERCP-related complications (hypotension, severe bradycardia, hypoxia, myocardial infarction, cerebral infarction) occurred in five patients from group B and three from group A. Post-ERCP pancreatitis occurred in one patient from group A and bleeding in one from group B. In univariate analysis, old age (≥ 80 years), American Society of Anesthesiologists score ≥ 3, and DASI < 10 were statistically significant predictors for overall serious events related to ERCP. In the multivariate analysis, DASI < 10 (only manage to ambulate) was independent predictor for overall serious events related to ERCP. DASI score is useful predictor for the feasibility assessment of safe ERCP in the elderly patients.


Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.
Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.


Cloning of adriamycin-resistant related (arr) gene in an adriamycin-resistant L1210 variant.
A partial fragment of novel sequence (arr, adriamycin-resistant related) was previously identified using the differential display (DD)-PCR technique with adriamycin-resistant L1210 variant (L1210AdR), which shows a typical multidrug resistant (MDR) phenotypes. The present research shows the isolation of full length arr cDNA sequence. To clone the full length cDNA of arr gene, DD-PCR fragments were subjected to 5'- and 3'-Rapid Amplification of cDNA End (RACE) method. The cloned arr cDNA consisted of 770 bases and contained an open reading frame of 153 bases, encoding a protein of 51 amino acid with the molecular mass of 4 kDa by in vitro translation reactions. Northern blot analysis showed that a 770 bases transcript arr gene was overexpressed in adriamycin-resistant L1210 variant, but not in the parent suggesting that the arr gene may be involved in the adriamycin-resistant phenotypes.


Deep Learning-Assisted Quantitative Susceptibility Mapping as a Tool for Grading and Molecular Subtyping of Gliomas.
This study aimed to explore the value of deep learning (DL)-assisted quantitative susceptibility mapping (QSM) in glioma grading and molecular subtyping. Forty-two patients with gliomas, who underwent preoperative T2 fluid-attenuated inversion recovery (T2 FLAIR), contrast-enhanced T1-weighted imaging (T1WI + C), and QSM scanning at 3.0T magnetic resonance imaging (MRI) were included in this study. Histopathology and immunohistochemistry staining were used to determine glioma grades, and isocitrate dehydrogenase (IDH) 1 and alpha thalassemia/mental retardation syndrome X-linked gene (ATRX) subtypes. Tumor segmentation was performed manually using Insight Toolkit-SNAP program (www.itksnap.org). An inception convolutional neural network (CNN) with a subsequent linear layer was employed as the training encoder to capture multi-scale features from MRI slices. Fivefold cross-validation was utilized as the training strategy (seven samples for each fold), and the ratio of sample size of the training, validation, and test dataset was 4:1:1. The performance was evaluated by the accuracy and area under the curve (AUC). With the inception CNN, single modal of QSM showed better performance in differentiating glioblastomas (GBM) and other grade gliomas (OGG, grade II-III), and predicting IDH1 mutation and ATRX loss (accuracy: 0.80, 0.77, 0.60) than either T2 FLAIR (0.69, 0.57, 0.54) or T1WI + C (0.74, 0.57, 0.46). When combining three modalities, compared with any single modality, the best AUC/accuracy/F1-scores were reached in grading gliomas (OGG and GBM: 0.91/0.89/0.87, low-grade and high-grade gliomas: 0.83/0.86/0.81), predicting IDH1 mutation (0.88/0.89/0.85), and predicting ATRX loss (0.78/0.71/0.67). As a supplement to conventional MRI, DL-assisted QSM is a promising molecular imaging method to evaluate glioma grades, IDH1 mutation, and ATRX loss. The online version contains supplementary material available at 10.1007/s43657-022-00087-6.


Estrogen activates raf-1 kinase and induces expression of Egr-1 in MCF-7 breast cancer cells.
We have investigated whether the raf-1 kinase, a downstream mediator of both receptor tyrosine kinase and protein kinase C signalling, is activated by estrogen (E2) in an estrogen receptor positive human breast cancer cell line. Autophosphorylation of raf-1 kinase was studied after treatment of MCF-7 cells with E2. E2-deprived cells contained low levels of raf-1 kinase activity. Treatment of cells for 1 min with E2 resulted in raf-1 autophosphorylation which was maximal within 5 min. Western blot analysis showed that raf-1 undergoes an electrophoretic mobility shift following E2 treatment. Egr-1 is a zinc finger-containing transcription factor which is expressed in association with raf-1 activation. Untreated MCF-7 cells expressed low levels of Egr-1 while E2 treatment resulted in an induction of egr-1 mRNA expression. These kinetics followed closely behind the E2 induction of c-myc mRNA. Egr-1 protein was similarly low in E2-deprived MCF-7 cells and was transiently increased following E2 treatment. Several studies have suggested that kinase activity may play a role in estrogen receptor (ER) activation. While activated v-raf failed to augment ER activation of transcription in transient transfection assays, a dominant negative mutant of raf-1 inhibited E2-induced transcription by 50% primarily as a result of increased baseline levels of E2 independent transcription. The results show that E2 can induce raf-1 kinase activity in MCF-7 breast cancer cells associated with the expression of an early growth response gene and modulation of ER signalling.


Renal response to metabolic alkalosis induced by isovolemic hemofiltration in the dog.
We describe a new model of chloride-depletion alkalosis (CDMA), in which the method of induction of alkalosis does not itself cause a direct alteration in sodium and fluid balance. We have used this model, which is based on hemofiltration techniques in the dog, to study the immediate response of the kidney to the induction of CDMA. Normal dogs maintained with a NaCl-free diet for several days underwent hemofiltration of 50 ml/kg over a 35 minute period. The hemofiltrate was replaced ml for ml with a solution containing sodium and potassium in the same concentrations as found in each animal's plasma water. In control animals, the replacement solution contained chloride and bicarbonate in the same ratio as in the plasma; in the experimental (CDMA) animals the replacement solution contained bicarbonate as the only anion. In the control group, the procedure of hemofiltration coupled with isovolemic replacement caused no appreciable changes in plasma composition, urinary excretion rates, GFR, or tubular handling of bicarbonate. In the CDMA group, 106 +/- 8.4 mEq of chloride were removed in exchange for bicarbonate. A marked metabolic alkalosis resulted, plasma bicarbonate concentration increasing from 21.9 +/- 0.6 to 33.3 +/- 0.6 mEq/liter. The hemofiltration procedure itself, by design, did not alter sodium or fluid balance. Nevertheless, cumulative urinary sodium excretion increased over 2.5 hours by 23.0 +/- 6.4 mEq. A natriuresis of this magnitude is equivalent to a loss of ECF volume of approximately 200 ml. GFR did not change significantly. The rate of tubular reabsorption of bicarbonate increased significantly from 1209 +/- 82 to 1559 +/- 148 mu Eq/min in CDMA animals.(ABSTRACT TRUNCATED AT 250 WORDS)


A Longitudinal Study of Well-being of Older Europeans: Does Retirement Matter?
We examine determinants of financial and subjective well-being, in particular poverty and depression, among older individuals in Europe. We do so using the 2004, 2006, and 2010 waves of the Survey of Health Ageing and Retirement in Europe and estimating dynamic panel data and binary choice transition models. We find a number of common effects across financial and subjective well-being. Unemployment, disabilities, serious health conditions, lower education, being female, and not being married increase the probability of poverty or depression. Conversely, healthy individuals, those with higher levels of education, males, and married individuals have higher probabilities of exiting poverty or depression. The effect of retirement is of special policy interest. It turns out to be crucial to control for endogeneity (i.e. the possibility of reverse causality) of retirement. If we don't control for endogeneity, retirement appears to increase both the risk of poverty and of depression. Once we control for endogeneity using instrumental variables, these negative effects disappear and point to weak evidence that retirement induced through eligibility for retirement pensions may be protective against poverty and depression.


Clinical evaluation of β-TCP in the treatment of lacunar bone defects: a prospective, randomized controlled study.
The aim of this study was to investigate the potential wide application of beta tricalcium phosphate (β-TCP) only for bone defects as compared to allograft. 95 patients with a solitary bone cyst were randomly assigned to the treatment. A new radiographic scoring system was employed to calculate the biodegradation of bone graft and to evaluate the influence of multiple factors. At an average of 28.43 months after surgery, a radiographic semi-quantitative analysis revealed that the degradation rates of β-TCP and the allograft were comparable (p>0.05). Age, complication, packing methods and granule diameters have a significant influence on β-TCP degradation. The loose packing method and 3-5mm granule size should be employed in clinical practice. A histological analysis of biopsy showed that β-TCP supported the growth of fibrous tissue, vascular tissue, as well as bone tissue into the implants. The results proved that single β-TCP is an advantageous alternative to allografts for lacunar bone defect repair and would well guide the design and clinical application of the β-TCP.


Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial.
A single low dose (0.25 mg/kg) of primaquine is recommended as a gametocytocide in combination with artemisinin-based combination therapies for Plasmodium falciparum but its effect on post-treatment gametocyte circulation and infectiousness to mosquitoes has not been quantified. In this randomised, double-blind, placebo-controlled trial, 360 asymptomatic parasitaemic children aged 2-15 years were enrolled and assigned to receive: artemether-lumefantrine (AL) and a dose of placebo; AL and a 0.25 mg/kg primaquine dose; or AL and a 0.40 mg/kg primaquine dose. On days 0, 2, 3, 7, 10 and 14, gametocytes were detected and quantified by microscopy, Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA), and quantitative reverse-transcriptase PCR (qRT-PCR). For a subset of participants, pre- and post-treatment infectiousness was assessed by mosquito feeding assays on days -1, 3, 7, 10 and 14. Both primaquine arms had lower gametocyte prevalences after day 3 compared to the placebo arm, regardless of gametocyte detection method. The mean (95% confidence interval) number of days to gametocyte clearance in children with patent gametocytes on day 0 (N = 150) was 19.7 (14.6 - 24.8), 7.7 (6.3 - 9.1) and 8.2 (6.7 - 9.6) for the AL-placebo, the 0.25 mg/kg primaquine dose and the 0.40 mg/kg primaquine dose arms, respectively. While 38.0% (30/79) of selected gametocytaemic individuals were infectious before treatment, only 1/251 participant, from the AL-placebo group, infected mosquitoes after treatment. We observed similar gametocyte clearance rates after 0.25 and 0.40 mg/kg primaquine doses. Infectivity to mosquitoes after AL was very low and absent in primaquine arms. CLINICALTRIALS. NCT01935882.


Downregulation of transposable elements extends lifespan in Caenorhabditis elegans.
Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.


Compositionality and the angular gyrus: A multi-voxel similarity analysis of the semantic composition of nouns and verbs.
The cognitive and neural systems that enable conceptual processing must support the ability to combine (and recombine) concepts to form an infinite number of ideas. Two candidate neural systems for conceptual combination-the left anterior temporal lobe (ATL) and the left angular gyrus (AG)-have been characterized as "semantic hubs" due to both functional and anatomical properties; however, these two regions likely support different aspects of composition. Here we consider two hypotheses for the role of AG in conceptual combination, both of which differ from a putative role for the ATL in "feature-based" combinatorics (i.e., meaning derived by combining concepts' features). Firstly, we examine whether AG is more sensitive to function-argument relations of the sort that arise when a predicate is combined with its arguments. Secondly, we examine the non-mutually exclusive possibility that AG represents information carried on a verb in particular, whether this be information about event composition or about thematic relations denoted uniquely by verbs. We identified voxels that respond differentially to two-word versus one-word stimuli, and we measured the similarity of the patterns in these voxels evoked by (1) pairs of two-word phrases that shared a noun that was an argument, thus sharing function-argument composition (e.g. eats meat and with meat), in comparison with two-word phrases that shared only a noun, not an argument (e.g., eats meat and tasty meat); and (2) stimulus pairs that shared only an event (operationalized here as sharing a verb; e.g. eats meat and eats quickly), in comparison to both of the above. We found that activity patterns in left AG tracked information relating to the presence of an event-denoting verb in a pair of two-word phrases. We also found that the neural similarity in AG voxel patterns between two phrases sharing a verb correlated with subjects' ratings of how similar the meanings of those two verb phrases were. These findings indicate that AG represents information specific to verbs, perhaps event structure or thematic relations mediated by verbs, as opposed to argument structure in general.


Spin-orbit Ab initio investigation of the photodissociation of dibromomethane in the gas and solution phases.
A clear and reliable theoretical investigation on dibromomethane (CH(2)Br(2)) photodissociation is desired. The calculation must consider: (i) relativistic effects; (ii) the potential energy curves (PECs) of spin-orbit coupling states; (iii) geometry optimization by the method with both static and dynamic electron correlations; (iv) solvent effects on the photodissociation in the solution. All these have been considered in this study by state-of-the-art quantum chemical calculations. The experimentally observed photodissociation in the gas phase with products of spin-orbit-coupled states, Br((2)P(3/2)) and Br*((2)P(1/2)), was assigned by multi-state second order multiconfigurational perturbation theory in conjunction with spin-orbit interaction through complete active space state interaction (MS-CASPT2/CASSI-SO) PECs. The mechanisms of the experimentally observed photodissociation and photoisomerization in solvent were elucidated by the MS-CASPT2/CASSI-SO method combined with polarized continuum model of the solvent.


Social, emotional, and behavioral functioning in young childhood cancer survivors with chronic health conditions.
The cancer diagnosis and its intensive treatment may affect the long-term psycho-social adjustment of childhood cancer survivors. We aimed to describe social, emotional, and behavioral functioning and their determinants in young childhood cancer survivors. The nationwide Swiss Childhood Cancer Survivor Study sends questionnaires to parents of survivors aged 5-15 years, who have survived at least 5 years after diagnosis. We assessed social, emotional, and behavioral functioning using the Strengths and Difficulties Questionnaire (SDQ). The SDQ includes four difficulties scales (emotional, conduct, hyperactivity, peer problems), a total difficulties indicator, and one strength scale (prosocial). We compared the proportion of survivors with borderline and abnormal scores to reference values and used multivariable logistic regression to identify determinants. Our study included 756 families (response rate of 72%). Thirteen percent of survivors had abnormal scores for the total difficulties indicator compared to 10% in the general population. The proportion of survivors with abnormal scores was highest for the emotional scale (15% vs. 8% in the general population), followed by the peer problems scale (14% vs. 7%), hyperactivity (8% vs. 10%), and conduct scale (6% vs. 7%). Few survivors (4% vs. 7%) had abnormal scores on the prosocial scale. Children with chronic health conditions had a higher risk of borderline and abnormal scores on all difficulties scales (all p < 0.05). Most childhood cancer survivors do well in social, emotional, and behavioral life domains, but children with chronic health conditions experience difficulties. Therefore, healthcare professionals should offer specific psycho-social support to these survivors.


Intestinal hypomotility due to longitudinal enterotomy can be alleviated by transverse closure.
Heineke-Mikulicz (HM) strictureplasty is commonly used to treat short stenoses in Crohn's disease. However, the degree to which intestinal motility is maintained remains unclear. We compared the peristalsis and transport capacity of the sutured intestines with HM configuration and transverse (TS) and longitudinal (LS) incisions. The intestinal diameter, intraluminal pressure, and bead transit time of each sutured group were compared with that of the non-treatment (NT) group in the isolated proximal colon of rats. Propulsive contractions were induced using hydroxy-?-sanshool (HAS), a constituent of Japanese pepper. There was no change in the intestinal diameter between HM, TS, and NT groups ; however, it was significantly narrowed at the suture site and its distal side in the LS group. After HAS administration, the intestinal diameter at the suture site in the HM group was higher than that in the LS group. The intraluminal pressure was higher and the transit time was shorter in the HM group compared to those in the LS group. The HM configuration, which widens the incision site and distal diameter and shortens the cut surface of the circular muscle in the longitudinal direction, may help maintain basal and HAS-induced intestinal peristalsis and motility. J. Med. Invest. 70 : 180-188, February, 2023.


Reference values and determinants for handgrip strength in healthy subjects.
To determine reference values and associated factors for handgrip strength among healthy adults. Three hundred well nourished (SGA category A) subjects were studied, aged 18-90 years. Handgrip strength (HS) was determined using a hand dynamometer. Adductor pollicis muscle (APM) thickness and other anthropometric variables were also measured. Results were analyzed according to gender and age group. We carried out multiple linear regression in order to identify significant determinants of handgrip strength. HS is significantly associated with gender and decreases after age 60 years (p<0.001). Different reference values for each gender and age category are presented, for both dominant (DHS) and non-dominant hands (NDHS). APM showed a strong correlation with HS (R(2)=0.71 and 0.70, for DHS and NDHS, respectively). This association remained significant after adjustment for other variables such as gender, age and body mass index. Reference values are needed to allow the use of HS as a muscular function assessment tool. Values should be stratified by gender and age group. The combined use of HS and APM may be useful as a method for nutritional assessment.


Trends in incidence of primary malignant brain tumors in USA, 1981-1990.
There has been considerable controversy regarding whether a recent observed rise in brain tumor incidence is real and so suggestive of increasing exposure to environmental carcinogens, or whether it is largely explainable by changes in diagnostic technology, particularly the introduction of computerized axial tomography (CT) scans in the 1970s. We analysed data from the US Surveillance, Epidemiology, and End Results (SEER) Program to investigate whether there was a rise of brain tumor incidence during 1981-1990, the period after CT scans became extensively available, and if so, the rates of which specific histologic subtypes have risen. Age- and sex-specific, as well as age-adjusted incidence rates were calculated for each brain tumor histologic subtype. Regression analysis was used to estimate age-adjusted incidence rate ratios (RR) for different periods and to examine time trends. For all histologic subtypes, the incidence rates increased with age. Regarding time trends, lymphomas in men increased in all age groups during the study period with the age-adjusted rate ratio reaching 5.6 (95% CI: 3.7-8.3) for 1989-1990 as compared to 1981-1982. Lymphoma in women and glioblastoma multiforme in both sexes also appear to have increased, particularly in the elderly. Other histologies did not show any time trends in the age-specific or age-adjusted analyses. Our histology-specific analysis is not suggestive of any significant increase in the incidence of brain tumors during 1980-1990, except for lymphomas in men.


Surgical Management of Gastrogastric Fistula After Roux-en-Y Gastric Bypass: 10-Year Experience.
Gastrogastric fistula (GGF) occurs in 1-6% of patients who undergo Roux-en-Y gastric bypass (RYGB) for morbid obesity. The pathophysiology may be related to gastric ischemia, fistula, or ulcer. The purposes of the study are to describe the principles of management and to review the literature of this uncommon complication. The setting of this study is University Hospital, France. We conducted a retrospective review of all patients' records with a diagnosis of GGF after RYGB between January 2004 and November 2014. During the study period, 1273 patients had RYGB for morbid obesity. Fifteen patients presented with a symptomatic GGF (1.18%). The average interval from surgery to presentation was 28 months (22-62). A history of marginal ulcer or anastomotic leak was present in nine patients (60%). The most common presentation was weight regain (80%), followed by pain (73.3%). Two types of fistulas were identified, an exclusively GGF (high) and a gastro-jejuno-gastric fistula (low). High GGF, frequently associated with dilatation of the gastric pouch, was treated by a sleeve of the pouch and sleeve resection of the remnant stomach (nine patients). Low GGF was treated with gastric resection coupled with a revision of the gastrojejunal anastomosis (six patients). All patients were treated laparoscopically with no conversion to laparotomy. The average length of postoperative hospital stay was 5.2 days (range 3-10). GGF after RYGB is a rare complication. Its pathophysiology remains unclear. Surgical management is the definitive treatment.


Antipeptide antibodies toward the extracellular domain of insulin receptor beta-subunit.
In order to investigate structure and function of beta-subunit extracellular portion, four polyclonal antibodies (AP1, AP2, AP3 and AP4) toward peptides comprised in this region were generated. None of them recognizes native human and rat insulin receptor both in vitro and in whole cells. Two antibodies, AP1 and AP2, immunoprecipitate isolated (DTT-reduced) human beta-subunits and bind to human IM-9 cell after alpha-subunit tryptic cleavage. Only AP1 recognizes rat beta-subunit both in vitro and in trypsin treated rat FAD cells. These findings suggest that: (i) the extracellular portion of the insulin receptor beta-subunit is partially covered by the alpha-subunit in human and rat native insulin receptors; (ii) human and rat beta-subunit extracellular domains are different, at least in the amino acid sequence corresponding to residues 785-796 of the human insulin receptor.


Transosseous versus transmuscular repair of the posterior soft tissue in primary hip arthroplasty: a meta-analysis.
During the posterior approach, it has been shown that a significant reduction in dislocation rate can be achieved with the repair of the posterior soft tissue. However, no consensus exists about the best way to perform this repair. This review aimed to compare the transosseous with transmuscular repair of the posterior soft tissue in total hip arthroplasty (THA). We conducted a meta-analysis to identify studies involving transosseous versus transmuscular repair of the posterior soft tissue in THA in electronic databases, including Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, Wanfang database, up to July 2020. Finally, we identified 1417 patients (1481 hips) assessed in seven studies. Compared with transmuscular repair, transosseous repair resulted in less incidence of dislocation (P = 0.003), less blood loss during operation (P < 0.00001) and lower VAS score within 3 months (P = 0.02). There were no significant differences in terms of trochanteric fracture rate (P = 0.56), Harris hip score at 3 months (P = 0.35) and 6 months (P = 0.89), VAS score within 6 months (P = 0.53), and operation time (P = 0.70) between two groups. The lower dislocation rate, less blood loss, and lower VAS scores after operation supported transosseous repair's superiority to transmuscular repair. Besides, no additional medical cost and operating time were associated with transosseous repair compared with transmuscular repair. Hence, we recommend that transosseous repair be chosen first by orthopedists when performing reconstruction of the posterior soft tissue in THA via a posterolateral approach. Given the relevant possible biases in our meta-analysis, we required more adequately powered and better-designed RCT studies with long-term follow-up to reach a firmer conclusion.


SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report.
Twenty-eight patients with drug resistant temporal lobe epilepsy (DRTLE) were studied using single photon emission computed tomography (SPECT) using xenon-133 inhalation and Tc99m-d, 1-HMPAO with TOMOMATIC 64 as part of a presurgical evaluation programme. The visually evaluated flow-images were studied after blinding and the results subsequently compared to the EEG, MRI and CT scanning studies. In 24 patients a significant low flow region was seen in one temporal lobe. The SPECT result corresponded to the EEG findings in all but 6 patients. In 2 of these patients no side localization was indicated by EEG, while in four patients the EEG suggested that the opposite side was epileptogenic. Ictal SPECT and MRI/CT agreed with the resting SPECT study in three patients, while one patient has remained undiagnosed with respect to side-localization. In 14 patients discordance between SPECT and the CT scan was observed, but in 11 of these patients the SPECT study correlated with the other focal diagnostic tools. In 11 of the 21 patients studied by MRI, the results corresponded to SPECT; in 7 of the 10 which did not correspond, ictal studies of EEG and SPECT defined the side, in four of these 7 patients. Using the neuroimaging tools in concert 16 patients have been selected for surgery. All patients have benefited from surgery. These preliminary results correspond favourably with earlier studies comparing SPECT and PET with CT, MR and EEG.


Homology modeling, functional annotation and comparative genomics of outer membrane protein H of Pasteurella multocida.
Pasteurella multocida is an important pathogen of animals and humans. Outer Membrane Protein (Omp) H is a major conserved protein in the envelope of P. multocida and has been commonly targeted as a protective antigen. However, not much is known about its structure and function due to the difficulties that are typically associated with obtaining sufficient amounts of purified prokaryotic transmembrane proteins. The present work is aimed at studying the OmpH using an in silico approach and consolidate the findings in light of existing experimental evidences. Our study describes the first 3D model of the P. multocida OmpH obtained through a combination of several in silico modeling approaches. From our results, OmpH of P. multocida could be classified as a homotrimeric, 16 stranded, β-barrel porin involved in the non-specific transport of small, hydrophilic molecules, serving essential osmoregulatory function. Moreover, very small homologous sequences could be identified in the host proteome, strengthening the probability of a successful OmpH-based vaccine against the pathogen with remote chances of cross-reaction to host proteins.


Development of a diphasic dialysis method for the extraction/purification of residues of ethinylestradiol in hair of cattle, and determination by gas chromatography-tandem mass spectrometry.
A confirmatory method for the analysis of ethinylestradiol extracted from cattle hair was developed. After the extraction of the xenobiotic from the hair, by using alkaline digestion, the purification of the extract was carried out by employing diphasic dialysis. For the optimization of the technique several parameters was evaluated such as pH, extraction solvents, temperatures, times and agitation speeds. The detection and confirmation of the steroid was accomplished by using a GC-MS2 ion trap system after trimethylsilylation. The calibration curve was linear over the range of 4-20 ng/g. The detection and quantification limit were 0.52 and 0.80 ng/g respectively; with recoveries up to 94%.


Low polarity ligands of sex hormone-binding globulin in pregnancy. Part I--Characterization.
Certain previously unidentified substances of low polarity binding to the sex hormone binding globulin (SHBG) in pregnancy were investigated. This material consisted of four major peaks (designated 1a, 1b, 2 and 3) as defined in maternal serum on Sephadex LH-20 chromatography. They were characterized with respect to changes in their concentration at various gestational ages and at premature and term labour in maternal serum, cord serum, placenta and maternal urine. Levels were much higher in placenta than in serum, suggesting that all four peaks were of placental origin. In the serum of mothers not in labour, while there was a significant increase in the mean serum concentration of peak (1a + 1b) and peak 3 for 12-24 weeks to 30-38 weeks gestation, there was no significant difference in the mean level of peak 2. However, there was a significant decrease in the serum levels of peak 2, but not peaks (1a + 1b) and 3, from 30-38 weeks gestation to 39-41 weeks gestation (P less than or equal to 0.05). In the serum of mothers in premature labour (30-38 weeks gestation), the levels of peak 2 but not those of peak (1a + 1b) and 3, were decreased (P less than or equal to 0.01) compared to those not in labour. These findings are consistent with the identification of peak 1a as 5 alpha-dihydroprogesterone, peak 1b as progesterone and peak 3 as 2-methoxyestrone as described in part 2. The decrease in the levels of peak 2 (for which the identification remains unconfirmed) in association with premature and impending term spontaneous labour suggest that it may be involved in the maintenance of pregnancy.


Interaction between rat alpha 1 fetoprotein and fluorescent derivatives of estrone in relation to the position and type of the fluorescent label.
A series of derivatives of estrone with fluorescent dyes (dansyl or coumarin) coupled at different positions on the steroid molecule, have been synthesized. These derivatives were tested for their quantum yields and their binding properties were determined with respect to rat alpha 1 fetoprotein. Derivatives at C-3 (estrone-3-hemisuccinate-dansyl-cadaverine and estrone-3-dansyl) compete with estrone for binding to the fetal protein; however derivates of estrone at C-6 (estrone-6-carboxymethyloxime-dansyl-cadaverine) and at C-17 (estrone-17-carboxymethyloxime-coumarine, estrone-17-carboxymethyloxime-dansyl-cadaverine and estrone-17-dansyl-hydrazine) compete poorly or not at all. The association constant of the radioactive derivative estrone-3-dansyl [3H] with rat alpha 1 fetoprotein was measured directly: the same number of high affinity binding sites (0.6) as that for estrone was found with an apparent association constant of 3.7 X 10(6) M-1. In addition to the high affinity binding sites, a low affinity class of binding sites was found which corresponds to the binding of the dansyl fraction of the fluorescent steroid derivative.


Is There a Cognitive Decline in Pediatric Patients Following Epilepsy Surgery?
Epilepsy surgery is currently the only way to cure drug-resistant epilepsy (DRE). The loss of epileptic activity or its propagation in the developing brain may not only result in seizure freedom but also be associated with further positive effects. Here, we analyzed the cognitive development of children and adolescents with DRE after epilepsy surgery. We evaluated retrospectively the cognitive development of children and adolescents before and after epilepsy surgery. Fifty-three children and adolescents underwent epilepsy surgery at a median age of 7.62 years. Overall seizure freedom was 86.8% at a current median observation period of 20 months. Presurgically, 81.1% had the clinical diagnosis of cognitive impairment, which was confirmed by standardized tests in 43 of 53 patients (76.7%). Further 10 patients had severe cognitive impairment rendering a standardized test impossible. The median intelligence quotient (IQ)/development quotient value was 74. After surgery, caretakers reported developmental progress in all patients, whereas the median IQ decreased slightly (P = 0.404). In eight patients the IQ points decreased after surgery; however, their individual raw scores increased in line with their reported increase in cognitive abilities. We did not detect any cognitive deterioration in children following epilepsy surgery. A loss of IQ points did not correspond to a real loss of cognitive abilities. These patients developed more slowly than age-matched peers with an average development speed but profited individually as seen in their raw scores. Therefore, an individual analysis of raw scores is relevant to assess the cognitive development after surgery.


[Health and illness in the country, state NRW, and its communities. Results from the 2009 German Microcensus].
The health-for-all policy framework needs data for action. Results from the German Microcensus can be extrapolated to the population at the country, state ("Bundesländer"), and community levels. Most of the information in the 2009 Microcensus was given under the statutory obligation; providing health information in the supplementary program was optional. The selection rate was 1% of the population. The Microcensus' continuous sampling method during the year, thus, determines illness rates as an average for the year. There are distinct health disparities between not only the states but also between communities in North Rhine-Westphalia. Annual average illness rates for 2009 are associated in NRW with influencing social factors, e.g., education. Illness rates rise with decreasing net income for the past month. Blue-collar workers suffered more often from illness or accident injuries at the time. The levels of illness in the overall employable population increase in the communities of NRW with the proportion of inhabitants who receive governmental financial aid or unemployment benefits to secure their basic livelihood. The Microcensus has the potential to be a source for systematic and harmonized monitoring concerning health in the country, states, and communities of Germany.


Effects of anterior lumbar spinal fusion on the distribution of nerve endings and mechanoreceptors in the rabbit facet joint: quantitative histological analysis.
The purpose of this study was to investigate the density and distribution of neural endings in rabbit lumbar facet joints after anterior spinal fusion and to evaluate the effects of intervertebral immobilization. An extraperitoneal approach was applied, and L5/6 was fixed with a plate and screws. Bilateral L4/5, L5/6, and L6/7 facet joint capsules were harvested from the rabbits 4, 8, and 16 weeks postoperatively. Capsular tissues were processed using a modified gold chloride staining method, and the specimens were sliced into 15-micro m sections. All sections were analyzed microscopically, and neural ending numbers per unit volume were calculated. Three types of neural ending were identified in each specimen: Pacinian corpuscles, Ruffini corpuscles, and free nerve endings. In the L5/6 fusion segment there was a significant decrease in the number of Pacinian corpuscles at 4 weeks and of Ruffini corpuscles at 4, 8, and 16 weeks after the fusion compared with the control; and in the L4/5 upper adjacent segment there was a significant increase in the number of free nerve endings. The number of Ruffini endings for the L6/7 lower adjacent segment was significantly lower more than 8 weeks after the fusion. These results suggest that immobilization of the intervertebral segment causes a reduction in the number of mechanoreceptors in the facet joint capsules because of the reduction in mechanical stimulation. Moreover, in the upper adjacent facet joint there may be neural sprouting caused by nociceptive stimulation.


Cellular Fatty Acid Analysis in Macrophage Using Stable Isotope Labeling.
Fatty acids (FAs) are essential for building complex lipids, posttranslational modifications, and energetics. FAs can be imported from extracellular sources or synthesized by cells. The analysis of fatty acid methyl esters (FAMEs) by gas chromatography-mass spectrometry (GC-MS) allows for the quantitative analysis of long-chain and very-long-chain fatty acid content of cells. When coupled with isotopic labeling, this approach can elucidate the synthetic pathways being engaged by the cells, and the relative contribution of synthesis and import to maintain lipid content. Here, we describe a method for total cellular fatty acid analysis in macrophages.


Biomechanical testing of rectangular humeral shaft prosthesis: higher torsional stability without increased fracture risk.
Rectangular cementless femur shaft prostheses have a higher primary stability than round shafts. A novel rectangular humeral shaft design was tested with two questions: does the rectangular design cause a higher fracture risk during implantation than round designs, and does it increase the torsional stiffness? Two series with six paired human humeri (total 24) were tested on one side with the rectangular shaft and on the contralateral side with a round shaft. In the first series, the shaft implantation was carried out with a constant speed of 100 mm/min and the maximum force was measured when the fracture occurred. In the second series, the implants were preloaded with 50 N and then rotated at 2° per second with monitoring of the torsional torque. The maximum force at fracture showed no significant difference for the two designs (p = 0.34). Higher age and low bone density reduced the force required for fracture. The rectangular shaft showed significant higher torsional moments (p < 0.05). In biomechanical testing, the rectangular shaft had a significantly higher primary torsional stability than the round shaft without a higher risk of fracture during cementless implantation. Fracture risk and torsional stability are influenced by age and bone density.