Rasch Analysis of the Activities-Specific Balance Confidence Scale in Older Adults Seeking Outpatient Rehabilitation Services.
Background The Activities-specific Balance Confidence (ABC) scale measures confidence in performing various ambulatory activities without falling or experiencing a sense of unsteadiness. Objectives This study (1) examined the ABC scale (0-100) using Rasch analysis, (2) assessed statistically reliable change, and (3) developed a functional staging to guide clinical interpretation of a patient's improvement. Methods The authors examined rating-scale structure, item difficulty hierarchy, item fit, person-item match, separation index, differential item functioning, test precision, and unidimensionality. Additionally, this cross-sectional study of 5012 older patients seeking outpatient rehabilitation therapy in 123 clinics estimated the minimal detectable change and developed a functional staging. Results The item "walk outside on icy sidewalks" was the most difficult item, while the item "reach for a small can off a shelf at eye level" was the easiest item. Overall, average patient ability estimates of 56.2 ± 20.3 were slightly higher than the average item difficulty estimates of 45.9 ± 7.8. With a separation index equal to 3.65, the ABC scale items can differentiate individuals into 5.2 statistically distinct strata. Most ABC scale items were free of differential item functioning. For example, "walk outside on icy sidewalks" was easier for patients who were underweight. Results supported unidimensionality of the ABC scale, with the first factor explaining 77% of the total variance. The estimated minimal detectable change was 15 points. The authors provided an example of functional staging application. Conclusion Results supported sound psychometric properties and clinical usage of the ABC scale for older adults seeking outpatient rehabilitation therapy. J Orthop Sports Phys Ther 2018;48(7):574-583. Epub 30 Mar 2018. doi:10.2519/jospt.2018.8023.


[Reliability of assessment of audible stuttering behavior].
The authors examine the essential aspects of the behaviour of the stutterer as perceived by the ear and discuss the reliability of the appreciation. The method of molecular analysis of speech samples of children aged from 7 to 12 years is described. The conclusion is that using this method, four out of the six categories of children examined show complete concordance and can be repeated as required; this is particularly true insofar as elongations, blockages, repetitions and interjections are concerned. However, one cannot consider as valid criteria the length of the pauses and the quality of breathing during phonation.


Multivoxel 1H-MR Spectroscopy Biometrics for Preoprerative Differentiation Between Brain Tumors.
We investigated multivoxel proton magnetic resonance spectroscopy (1H-MRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-grade glioma (LGG) and high-grade glioma (HGG). In total, 33 patients (HGG, 14; LGG, 9; and 10 MET) were included. 1H-MRS imaging (MRSI) data were assessed and neurochemical profiles for metabolites N-acetyl aspartate (NAA) + NAAG(NAA), Cr + PCr(total creatine, tCr), Glu + Gln(Glx), lactate (Lac), myo-inositol(Ins), GPC + PCho(total choline, tCho), and total lipids, and macromolecule (tMM) signals were estimated. Metabolites were reported as absolute concentrations or ratios to tCho or tCr levels. Voxels of interest in an MRSI matrix were labeled according to tissue. Logistic regression, receiver operating characteristic, and Kaplan-Meier survival analysis was performed. Across HGG, LGG, and MET, average Ins/tCho was shown to be prognostic for overall survival (OS): low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (log rank < 0.007). Lip/tCho and Ins/tCho combined showed 100% sensitivity and specificity for both HGG/LGG (P < .001) and LGG/MET (P < .001) measured in nonenhancing/contrast-enhancing lesional tissue. Combining tCr/tCho in perilesional edema with tCho/tCr and NAA/tCho from ipsilateral normal- appearing tissue yielded 100% sensitivity and 81.8% specificity (P < .002) for HGG/MET. Best single biomarker: Ins/tCho for HGG/LGG and total lipid/tCho for LGG/MET showed 100% sensitivity and 75% and 100% specificity, respectively. HGG/MET; NAA/tCho showed 75% sensitivity and 84.6% specificity. Multivoxel 1H-MRSI provides prognostic information for OS for HGG/LGG/MET and a multibiometric approach for differentiation may equal or outperform single biometrics.


Psychiatric morbidity amongst adolescents in a Nigerian juvenile correctional facility.
The high occurrence of psychiatric disorders amongst adolescents within the Juvenile Justice System (JJS) has been confirmed. Most of the available data are from developed countries and some of them focus on just a single psychiatric disorder which may not be representative of the situation in low-income countries, hence the need for more studies in developing countries, including Nigeria. The study aimed to determine the prevalence of psychiatric disorders amongst adolescent residents of a correctional facility. The study was carried out at a Borstal Institution in North-Central Nigeria. A descriptive cross-sectional study design was used. One hundred and twenty adolescents were assessed using the socio-demographic pro forma questionnaire designed by the researcher and the Kiddies Schedule for Affective Disorders and Schizophrenia (KSADS-PL). Data were analysed using EPI-INFO 4.06 d version 6.04 software. A total of 62.5% of the male respondents were older than 15 years. The percentage of respondents with a psychiatric disorder was 82.5%. The rate of psychiatric disorders was high with disruptive behaviour disorders being the most common at 40.8%, others were substance use disorders (15.8%), anxiety disorders (14.2%), psychosis (6.7%) and mood disorders (5%). This study has established a high prevalence rate of psychiatric disorders amongst incarcerated adolescents. This is in line with the findings of numerous studies worldwide. This study has identified the need to increase awareness and knowledge about the high morbidity of mental disorders in growing juvenile detainee populations. This will allow early identification of adolescents at risk of psychiatric disorders and ensure efficient resource distribution of both JJS service and mental healthcare. Effective and appropriate interventions have shown to improve overall health, quality of life and reduce the rate of recidivism amongst incarcerated juveniles.


Functions of beta2-adrenergic receptor in human periodontal ligament cells.
Adrenergic receptors (ARs) are receptors of noradrenalin and adrenalin, of which there are nine different subtypes. In particular, β2 adrenergic receptor (β2-AR) is known to be related to the restoration and maintenance of homeostasis in bone and cardiac tissues; however, the functional role of signaling through β2-AR in periodontal ligament (PDL) tissue has not been fully examined. In this report, we investigated that β2-AR expression in PDL tissues and their features in PDL cells. β2-AR expressed in rat PDL tissues and human PDL cells (HPDLCs) derived from two different patients (HPDLCs-2G and -3S). Rat PDL tissue with occlusal loading showed high β2-AR expression, while its expression was downregulated in that without loading. In HPDLCs, β2-AR expression was increased exposed to stretch loading. The gene expression of PDL-related molecules was investigated in PDL clone cells (2-23 cells) overexpressing β2-AR. Their gene expression and intracellular cyclic adenosine monophosphate (cAMP) levels were also investigated in HPDLCs treated with a specific β2-AR agonist, fenoterol (FEN). Overexpression of β2-AR significantly promoted the gene expression of PDL-related molecules in 2 to 23 cells. FEN led to an upregulation in the expression of PDL-related molecules and increased intracellular cAMP levels in HPDLCs. In both HPDLCs, inhibition of cAMP signaling by using protein kinase A inhibitor suppressed the FEN-induced gene expression of α-smooth muscle actin. Our findings suggest that the occlusal force is important for β2-AR expression in PDL tissue and β2-AR is involved in fibroblastic differentiation and collagen synthesis of PDL cells. The signaling through β2-AR might be important for restoration and homeostasis of PDL tissue.


Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes.
Human red cell membrane Ca2+-stimulatable, Mg2+-dependent adenosine triphosphatase (Ca2+-ATPase) activity and its response to thyroid hormone have been studied following exposure of membranes in vitro to specific long-chain fatty acids. Basal enzyme activity (no added thyroid hormone) was significantly decreased by additions of 10(-9)-10(-4) M-stearic (18:0) and oleic (18:1 cis-9) acids. Methyl oleate and elaidic (18:1 trans-9), palmitic (16:0) and lauric (12:0) acids at 10(-6) and 10(-4) M were not inhibitory, nor were arachidonic (20:4) and linolenic (18:3) acids. Myristic acid (14:0) was inhibitory only at 10(-4) M. Thus, chain length of 18 carbon atoms and anionic charge were the principal determinants of inhibitory activity. Introduction of a cis-9 double bond (oleic acid) did not alter the inhibitory activity of the 18-carbon moiety (stearic acid), but the trans-9 elaidic acid did not cause enzyme inhibition. While the predominant effect of fatty acids on erythrocyte Ca2+-ATPase in situ is inhibition of basal activity, elaidic, linoleic (18:2) and palmitoleic (16:1) acids at 10(-6) and 10(-4) M stimulated the enzyme. Methyl elaidate was not stimulatory. These structure-activity relationships differ from those described for fatty acids and purified red cell Ca2+-ATPase reconstituted in liposomes. Thyroid hormone stimulation of Ca2+-ATPase was significantly decreased by stearic and oleic acids (10(-9)-10(-4) M), but also by elaidic, linoleic, palmitoleic and myristic acids. Arachidonic, palmitic and lauric acids were ineffective, as were the methyl esters of oleic and elaidic acids. Thus, inhibition of the iodothyronine effect on Ca2+-ATPase by fatty acids has similar, but not identical, structure-activity relationships to those for basal enzyme activity. To examine mechanisms for these fatty acid effects, we studied the action of oleic and stearic acids on responsiveness of the enzyme to purified calmodulin, the Ca2+-binding activator protein for Ca2+-ATPase. Oleic and stearic acids (10(-9)-10(-4) M) progressively inhibited, but did not abolish, enzyme stimulation by calmodulin (10(-9) M). Double-reciprocal analysis of the effect of oleic acid on calmodulin stimulation indicated noncompetitive inhibition. Addition of calmodulin to membranes in the presence of equimolar oleic acid restored basal enzyme activity. Oleic acid also reduced 125I-calmodulin binding to membranes, but had no effect on the binding of [125I]T4 by ghosts. The mechanism of the decrease by long chain fatty acids of Ca2+-ATPase activity in situ in human red cell ghosts thus is calmodulin-dependent and involves reduction in membrane binding of calmodulin.


[The role of magnetolaserotherapy in the correction of the adaptive potential of the brain in the children suffering absence seizures].
We have conducted a course of magnetic laser therapy targeted on the vegetative structures at the neck of the children suffering absence seizures in an attempt to optimize the functioning of the non-specific brain structures. The study has demonstrated that such treatment promotes normalization of the components of the orientation response to sound almost to the level observed in the healthy children. The alpha-index returned to the normal value as well.


The meteorology of cytokine storms, and the clinical usefulness of this knowledge.
The term cytokine storm has become a popular descriptor of the dramatic harmful consequences of the rapid release of polypeptide mediators, or cytokines, that generate inflammatory responses. This occurs throughout the body in both non-infectious and infectious disease states, including the central nervous system. In infectious disease it has become a useful concept through which to appreciate that most infectious disease is not caused directly by a pathogen, but by an overexuberant innate immune response by the host to its presence. It is less widely known that in addition to these roles in disease pathogenesis these same cytokines are also the basis of innate immunity, and in lower concentrations have many essential physiological roles. Here we update this field, including what can be learned through the history of how these interlinking three aspects of biology and disease came to be appreciated. We argue that understanding cytokine storms in their various degrees of acuteness, severity and persistence is essential in order to grasp the pathophysiology of many diseases, and thus the basis of newer therapeutic approaches to treating them. This particularly applies to the neurodegenerative diseases.


Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.
To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)-beta treatment. CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy-debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN-beta (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed. There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI -0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI -0.44, 1.02) before and during regular IFN-beta treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN-beta treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10). IFN-beta treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN-beta.


An integrated approach to assess air pollution threats to cultural heritage in a semi-confined environment: the case study of Michelozzo's Courtyard in Florence (Italy).
An example of an integrated approach to assess air pollution threats to cultural heritage in a semi-confined environment is presented in this work, where the monitoring campaign carried out at the Michelozzo's Courtyard (in Palazzo Vecchio, Florence, Italy) is used as a case study. A wide research project was carried out, with the main aim of obtaining the first quantitative data on air quality and microclimate conditions inside the Courtyard, and, if possible, identifying the main causes of degradation and suggesting appropriate conservation strategies. The investigation adopted a holistic approach involving thermographic measurements on the wall paintings, microclimatic analysis, gaseous pollutant monitoring, atmospheric particles characterisation and dry deposition compositional analysis. Attention was focused on the wall painting depicting the city of Hall because of its anomalous and critical conservation conditions, which are visible at a glance, due to the contrast between a wide darker zone around the central subject of the painting and external lighter areas.


The epizootiology of nematode parasites of sheep in a high-rainfall area of Zimbabwe.
Fifty-two untreated lambs from a contaminated flock were slaughtered at regular intervals throughout the year, and their gastro-intestinal tracts were examined for the presence of nematode parasites. Haemonchus contortus and Oesophagostomum columbianum were found to be of major importance. The incidence of Haemonchus rose to a peak and remained at a high level throughout the winter through the fourth larval stages of the parasite predominated at this stage. Oesophagostomum columbianum was recovered in numbers unusually high for this species, the incidence of which remained at a relatively high level from March until October. The minor genera recovered were Trichostrongylus spp., Cooperia spp., Strongyloides papillosus and Trichuris ovis.


Primary cesarean section: factors related to postpartum infection.
Four hundred sixty-five primary cesarean sections (10.4% of total deliveries) performed during 1977 and 1978 were reviewed and compared with 465 vaginal deliveries to ascertain factors that may be related to postpartum infection. The overall morbidity (19.7%) related to postpartum infection in the primary cesarean section group was statistically different from the 2.4% morbidity in the vaginal group. Cross comparisons of the effect of membrane status, use of internal electronic monitoring, development of postpartum anemia, duration of active labor, and difference in patient populations showed that internal monitoring had little or no effect on the development of postpartum endometritis. However, the development of postpartum anemia, increased time between membrane rupture and delivery, and, most important, a significant difference in patient populations were believed to be related to the development of postpartum endometritis in both groups.


Functional Magnetic Resonance Imaging Study of Electroacupuncture Stimulating Uterine Acupoints.
Based on resting-state functional magnetic resonance imaging (rs-fMRI), to observe the changes of brain function of bilateral uterine points stimulated by electroacupuncture, so as to provide imaging basis for acupuncture in the treatment of gynecological and reproductive diseases. 20 healthy female subjects were selected to stimulate bilateral uterine points (EX-CA1) by electroacupuncture. FMRI data before and after acupuncture were collected. The ReHo values before and after acupuncture were compared by using the analysis method of regional homogeneity (ReHo) of the whole brain, so as to explore the regulatory effect of acupuncture intervention on brain functional activities of healthy subjects. Compared with before acupuncture, the ReHo values of the left precuneus lobe, left central posterior gyrus, calcarine, left lingual gyrus, and cerebellum decreased significantly after acupuncture. Electroacupuncture at bilateral uterine points can induce functional activities in brain areas such as the precuneus, cerebellum, posterior central gyrus, talform sulcus, and lingual gyrus. The neural activities in these brain areas may be related to reproductive hormone level, emotional changes, somatic sensation, and visual information. It can clarify the neural mechanism of acupuncture at uterine points in the treatment of reproductive and gynecological diseases to a certain extent.


Editorial: targeted drug delivery for cancer.
Cancer drug delivery is no longer simply wrapping the drug in new formulations for different routes of delivery. Knowledge and experience from other technologies such as nanotechnology, advanced polymer chemistry, and electronic engineering, are being brought together in developing novel methods of drug delivery. Advances in our knowledge of molecular biology of cancer and pathways involved in malignant transformation of cells are revolutionizing the approach to cancer treatment with a focus is on targeted cancer therapy. The newer approaches to cancer treatment not only supplement the conventional chemotherapy and radiotherapy but also aim to prevent damage to the normal tissues and overcome drug resistance. Innovative methods of cancer treatment require new concepts of drug delivery in cancer.


Spatial and temporal dynamics of Puumala hantavirus infection in red bank vole (Clethrionomys glareolus) populations in Belgium.
Dynamics of hantavirus infection and population densities in rodents were investigated from 1996 to 1999 in southern Belgium. Evidence of Puumala infection was restricted to Clethrionomys glareolus. Although the serotype was not determined, antibodies against hantavirus were also found in eight Apodemus sylvaticus. In fall 1996, the seroprevalence in C. glareolus was high (20.1%, 37 of 184) and the infection was widely distributed in the area studied whereas a focal occurrence of positive rodents and lower seroprevalence rates were recorded in spring 1997 (14.3%, six of 42), fall 1997 (6. 6%, 11 of 166), spring 1998 (6.4%, three of 47) and fall 1998 (6.7%, 11 of 165). A pullulation of rodents was observed in spring 1999 and was associated with a markedly higher seroprevalence in C. glareolus (47.7%, 189 of 396). In all seasons, infection rates in adults were higher than in juveniles and subadults. No significant difference of prevalence was recorded between males and females. In two trapping sites, the temporary disappearance of positive animals after a crash in rodent populations suggests that a threshold in density is necessary for the maintenance of the enzootic cycle.


Effects of endogenous ouabain on the development of hypertension in 1k1c hypertensive rats.
This study was designed to evaluate the role of endogenous ouabain (EO) in the development of hypertension in 1ktc (one kidney, one clip) hypertensive rats. First, the EO content of the serum of 1k1c hypertensive rats and normal Sprague-Dawley (SD) rats was detected by the enzyme linked immunosorbent assay method (ELISA). Second, blood pressure changes in the 1k1c rats were recorded directly after the 1k1c rats were injected randomly with anti-ouabain antibody, normal rabbit IgG, and normal saline, respectively. The results showed that EO levels in the serum of 1k1c hypertensive rats were significantly higher than those of normal SD rats (2.25 +/-0.92 microg/l vs. 1.12 +/- 0.17 microg/l, p< 0.01), and correlated significantly with systolic blood pressure (r= 0.59, p< 0.05). Anti-ouabain antibody was able to significantly decrease the blood pressure of 1k1c hypertensive rats in a dose-dependent manner, while normal rabbit IgG or normal saline was not. These results indicate that endogenous ouabain might play an important role in the development of hypertension in 1k1c hypertensive rats.


Using Neuropsychometric Measurements in the Differential Diagnosis of Specific Learning Disability.
The aim of this study was to develop a neuropsychometric battery for the differential diagnosis of specific learning disability (SLD), with specific respect to attention deficit hyperactivity disorder (ADHD), and to help resolve the conflicting results in the literature by an integrative utilization of scores on both the Bannatyne categories and neuropsychological tests. The sample included 168 primary school boys who were assigned to SLD (n=21), ADHD (n=45), SLD and ADHD (n=57), and control groups (n=45). The exclusion criteria were a neurological or psychiatric comorbidity other than ADHD, a level of anxiety and/or depression above the cutoff score, medication affecting cognitive processes, visual and/or auditory disorders, and an intelligence level outside the IQ range of 85-129. Psychometric scores were obtained from the SLD Battery and Wechsler Intelligence Scale for Children-Revised in the form of Bannatyne category scores. Neuropsychological scores were from the Visual-Aural Digit Span Test-Form B, Serial Digit Learning Test, Judgment of Line Orientation, and Mangina Test. The battery was called the Integrative Battery of SLD. The correctness of estimation for classifying cases into the diagnostic dyads (SLD/ADHD, SLD/SLD+ADHD, and SLD+ADHD/ADHD) by an integrative utilization of both the Bannatyne category scores (n=4) and scores from the four neuropsychological tests (n=10) was 92.4%, 81.4%, and 71.8%, respectively. These proportions were generally higher than those obtained using the Bannatyne category scores alone (86.4%, 75.5%, and 73.1%, respectively). The same trend was seen in the classification of children into diagnostic and control groups. However, the proportion of the correctness of estimation was higher than that obtained for the diagnostic dyads. When conducted using appropriately chosen research designs and statistical techniques and if confounding variables are sufficiently controlled, a neuropsychometric battery that includes capacities that relate to intelligence (Bannatyne categories) and those that relate to neurocognitive processes (neuropsychological tests) can be useful in the differential diagnosis of SLD.


Sociocultural influences on infant feeding decisions among HIV-infected women in rural Kwa-Zulu Natal, South Africa.
The promotion of exclusive breastfeeding for 6 months, followed by rapid transition to alternative food sources may be an important public health approach to the reduction of mother-to-child transmission of HIV through breastmilk. The basic ethical principle of 'informed choice' requires that HIV positive women are provided with adequate information about their options. However, information is only one factor that affects their decisions. The objective of this ethnographic study was to identify sociocultural influences on infant feeding decisions in the context of a large cohort study designed to assess the impact of a breastfeeding counselling and support strategy to promote exclusive breastfeeding on postnatal transmission of HIV in African women. Following an initial period of exploratory interviewing, ethnographic techniques were used to interview 22 HIV positive women about their views on infant feeding and health. Interviews were tape-recorded, transcribed and analysed with a text analysis program. Five themes of influences on feeding decisions emerged: (1) social stigma of HIV infection; (2) maternal age and family influences on feeding practices; (3) economic circumstances; (4) beliefs about HIV transmission through breastmilk; and (5) beliefs about the quality of breastmilk compared to formula. The study highlights the role of cultural, social, economic and psychological factors that affect HIV positive women's infant feeding decisions and behaviour.


A Biclique Approach to Reference-Anchored Gene Blocks and Its Applications to Genomic Islands.
We formalize a new problem variant in gene-block discovery, denoted Reference-Anchored Gene Blocks (RAGB), given a query sequence Q of length n, representing the gene array of a DNA element, a window size bound d on the length of a substring of interest in Q, and a set of target gene sequences [Formula: see text]. Our objective is to identify gene blocks in [Formula: see text] that are centered in a subset q of co-localized genes from Q, and contain genomes from [Formula: see text] in which the corresponding orthologs of the genes from q are also co-localized. We cast RAGB as a variant of a (colored) biclique problem in bipartite graphs, and analyze its parameterized complexity, as well as the parameterized complexity of other related problems. We give an [Formula: see text] time algorithm for the uncolored variant of our biclique problem, where m is the number of areas of interest that are parsed from the target sequences, and n and d are as defined earlier. Our algorithm can be adapted to compute all maximal bicliques in the graph within the same time complexity, and to handle edge weights with a slight [Formula: see text] increase to its time complexity. For the colored version of the problem, our algorithm has a time complexity of [Formula: see text]. We implement the algorithm and exemplify its application to the data mining of proteobacterial gene blocks that are centered in predicted proteobacterial genomic islands, leading to the identification of putatively mobilized clusters of virulence, pathogenicity, and resistance genes.


Comprehensive assessment of the genetic characteristics of small for gestational age newborns in NICU: from diagnosis of genetic disorders to prediction of prognosis.
In China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors. A cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children's Hospital of Fudan University, Shanghai, China. Among the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84-0.96] vs. AUC=0.74 [0.64-0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6-0.93] vs. AUC=0.53[0.29-0.76]; P=0.0117). SGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.


Impact of obesity on metabolic syndrome components and adipokines in prepubertal children.
To verify the impact of obesity on metabolic syndrome components and adipokine levels in prepubertal children. This cross-sectional study compared 30 obese, 31 overweight and 33 eutrophic children attending a university hospital-based outpatient pediatric clinic. Parameters assessed included glucose, serum lipids, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), glucose/insulin relation, adiponectin, and leptin. We compared the frequency of acanthosis nigricans and changes in waist, blood pressure, glucose, serum lipids, and insulin. The correlation between body mass index (BMI) z score and adipokines was evaluated. Among obese children, there was a difference in the mean values of HDL cholesterol and adiponectin, whereas among the eutrophic children, there was a difference in the mean values of insulin, HOMA-IR, glucose/insulin relation, and leptin (p < 0.001). A difference was also observed regarding the frequency of acanthosis nigricans and alteration in waist and HDL cholesterol (p < 0.005) in the obese group. The BMI z score showed a positive correlation with leptin (p < 0.001) and a negative correlation with adiponectin (p = 0.001). In multiple linear regression, this correlation was maintained only for leptin; HDL-cholesterol correlated with adiponectin (p = 0.007) and HOMA-IR correlated with both variables (p < 0.05). These findings provide evidence of the influence of obesity on metabolic syndrome components and on adipokine levels in prepubertal children, indicating that these components may contribute to the beginning of cardiovascular diseases.


Microfluidic monitoring of the growth of individual hyphae in confined environments.
Soil fungi have the ability to form large mycelial networks. They rely on the resources available in the soil to produce biomass and are able to degrade complex biomolecules. Some of them can even degrade recalcitrant organic pollutants and are considered as promising candidates for soil bioremediation strategies. However, the success of this approach depends on the ability of fungi to colonize the soil matrix, where they encounter spatial and temporal variations of confinement, humidity and nutrient concentration. In this paper, we present a study of fungal growth at the scale of single hyphae in a microfluidic device, allowing fine control of nutrient and water supply. Time-lapse microscopy allowed simultaneous monitoring of the growth of dozens of hyphae of Talaromyces helicus, a soil isolate, and of the model fungus Neurospora crassa through parallel microchannels. The distributions of growth velocity obtained for each strain were compared with measurements obtained in macroscopic solid culture. For the two strains used in the study, confinement caused the growth velocity to drop in comparison with unconfined experiments. In addition, N. crassa was also limited in its growth by the nutrient supply, while the microfluidic culture conditions seemed better suited for T. helicus. Qualitative observations of fungi growing in microfluidic chambers without lateral confinement also revealed that side walls influence the branching behaviour of hyphae. This study is one of the first to consider the confinement degree within soil microporosities as a key factor of fungal growth, and to address its effect, along with physicochemical parameters, on soil colonization, notably for bioremediation purposes.


Comparisons of brain, uterus, and liver mRNA expression for cytochrome p450s, DNA methyltransferase-1, and catechol-o-methyltransferase in prepubertal female Sprague-Dawley rats exposed to a mixture of aryl hydrocarbon receptor agonists.
Non-ortho polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) are ubiquitous environmental contaminants that exert their toxicity mostly through activation of the aryl-hydrocarbon receptor (AhR), and are referred to as AhR agonists. The objective was to study, by real time reverse-transcriptase-polymerase chain reaction (RT-PCR), the effects of postnatal exposure to a reconstituted mixture of AhR agonists present in breast milk (3 non-ortho PCBs, 6 PCDDs, and 7 PCDFs, referred to here-in-after as AhRM) on mRNA expression of estrogen receptor (ERalpha), enzymes involved with the metabolism of estrogens [catechol-o-methyltransferase (Comt), cytochrome P450 (Cyp)1A1, 1B1 and 2B1], and DNA methyltransferase-1 (Dnmt1), in brain areas, liver and uterus of immature female rats. Neonates were exposed by gavage during postnatal day (PND) 1-20 with dosages equivalent to 1, 10, 100, and 1000 times the estimated average human exposure level, and were sacrificed at PND 21. None of the end points were affected in uterine cross-sections, or in samples of uterine tissue layers collected by laser capture microdissection. At 1000x, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32% of control in the liver and hypothalamus, respectively. In the brain, Cyp1A1 was increased (409%) but ERalpha was reduced (66%). Similarly, mRNA abundance for Comt isoforms was reduced in the liver (45%) and brain areas (55-70%). AhRM at 100x, the lowest effective dose, exerted a 220% increase in brain cortex Comt [membrane bound (Mb)], a 219% increase in hepatic Cyp1B1, and a 63% decrease in hepatic Comt (soluble (S)+Mb). These results support the possibility that early exposure to environmental contaminants could lead to effects mediated by changes in DNA methylation and/or estrogen metabolism and signaling.


Third party monitoring for health in Afghanistan: the good, the bad and the ugly.
Third party monitoring (TPM) is used in development programming to assess deliverables in a contract relationship between purchasers (donors or government) and providers (non-governmental organisations or non-state entities). In this paper, we draw from our experience as public health professionals involved in implementing and monitoring the Basic Package of Health Services (BPHS) and the Essential Package of Hospital Services (EPHS) as part of the SEHAT and Sehatmandi programs in Afghanistan between 2013 and 2021. We analyse our own TPM experience through the lens of the three parties involved: the Ministry of Public Health; the service providers implementing the BPHS/EPHS; and the TPM agency responsible for monitoring the implementation. Despite the highly challenging and fragile context, our findings suggest that the consistent investments and strategic vision of donor programmes in Afghanistan over the past decades have led to a functioning and robust system to monitor the BPHS/EPHS implementation in Afghanistan. To maximise the efficiency, effectiveness and impact of this system, it is important to promote local ownership and use of the data, to balance the need for comprehensive information with the risk of jamming processes, and to address political economy dynamics in pay-for-performance schemes. Our findings are likely to be emblematic of TPM issues in other sectors and other fragile and conflicted affected settings and offer a range of lessons learnt to inform the implementation of TPM schemes.


Distribution and occurrence of myxomycetes on agricultural ground litter and forest floor litter in Thailand.
The ecological distribution and seasonal patterns of occurrence of myxomycetes associated with the microhabitats represented by agricultural ground litter and forest floor litter were investigated in six study sites in northern Thailand during Oct 2004-Oct 2005. Both specimens that developed under natural conditions in the field and specimens obtained in moist chamber cultures were considered. Agricultural study sites were a banana plantation, a mango orchard and a sweet corn farm, whereas forest study sites consisted of a lowland forest, a midelevation forest and a highland forest. Seventy species of myxomycetes representing 20 genera were collected, with 34 species recorded during the dry season and 58 species recorded during the rainy season. Distinct differences were apparent for numbers of positive moist chambers, numbers of species recorded from moist chambers, numbers of species recorded as field collections and numbers of field collections when data obtained for the two seasons were compared. In the dry season only three species were collected in the field, but the percentage of positive moist chamber cultures (129/180 or 72%) and number of species recorded (33) from these cultures were high. In contrast, during the rainy season, 52 species of myxomycetes were collected in the field but only 15 species were recorded from the much lower percentage (75/180 or 42%) of positive moist chambers cultures.


Magnetic resonance imaging in the assessment of medullary compression in achondroplasia.
Children with achondroplasia may be at increased risk of developing apneic episodes and of dying unexpectedly. The risks seem to be related to neural axis compression by an abnormal cranial base and may be complicated by the development of hydrocephalus. We used magnetic resonance imaging to study five children with achondroplasia. All of them demonstrated a discrepancy between the size of the brain stem and the foramen magnum. Comprehensive prospective assessment of infants with achondroplasia, including the use of new imaging techniques, will provide important information concerning the natural history of the relationship of the neural axis to the bony posterior fossa and upper cervical spine in this condition. It may also help to identify those patients at risk before the development of life-threatening medullary compression.


Trends in hospital admissions for chronic obstructive pulmonary disease over 16 years in Canada.
Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition, and the rate of hospital admissions for COPD is an indicator of the quality of outpatient care. We sought to determine long-term trends in hospital admissions for COPD in Canada. Using a comprehensive national database of hospital admissions in Canada, we identified those with a main discharge diagnosis of COPD for patients aged 40 years and older between 2002 and 2017. We calculated sex-specific, age-standardized trends in annual rates of hospital admissions for COPD separately for younger (40-64 yr) and older adults (≥ 65 yr). We used spline regression to examine changes in the admissions trends for each sex and age group. Over 16 years, 1 134 359 hospital admissions were for COPD. Between 2002 and 2017, the total number of admissions increased by 68.8%, from 52 937 to 89 384. The overall crude admission rate increased by 30.0%, from 368 to 479 per 100 000 population, and the sex-and age-standardized admission rate increased by 9.6%, from 437 to 479 per 100 000 population. Age-standardized rates increased by 12.2% among younger females, by 24.4% among younger males and by 29.8% among older females, but decreased by 9.0% among older males. Over the same period, the all-cause sex-and age-standardized admission rate declined by 23.0%. Hospital admissions for COPD have increased since 2010, even after adjusting for population growth and aging, and despite declining rates of all-cause hospital admissions. The secular increase in COPD admissions indicates that the burden of COPD on Canadian health care systems is increasing.


Cyclosporine and Vancomycin + Amikacin Induced Hot Kidney Appearance in a Young Adult and a Pediatric Patient.
The appearance of a hot kidney on bone scintigraphy is rare and can be seen due to various factors. In our clinic, we observed hot kidney appearance in two patients to whom technetium-99m methylene diphosphonate (Tc-99m MDP) whole body scan has been performed: a young male adult at the age of 18 who was diagnosed with acute lymphocytic leukemia with a presumptive diagnosis of avascular necrosis, and a 9-year-old girl with cystitis for a pre-diagnosis of osteomyelitis. The first patient had a history of cyclosporine usage and the second patient was being treated with amikacin + vancomycin. To the best of our knowledge, we present the first cases where hot-kidney appearance on Tc-99m MDP whole body scan due to the use of cyclosporin and amikacin + vancomycin is demonstrated.


Maintenance of peritoneal B-1a lymphocytes in the absence of the spleen.
Positive selection by autoantigens is believed to play an important role in the generation/maintenance of B-1a cells. Recently, it has been described that splenectomy results in the loss of an already established B-1a cell pool. To elucidate whether the spleen influences the peritoneal B-1a repertoire, we have analyzed the consequences of splenectomy in the recently established IgL-transgenic L2 mouse model. L2 mice are characterized by a severe block of B-2 development and predominance of B-1a cells, which exhibit a pronounced IgH oligoclonality, presumably due to positive selection by autoantigens. In this study, we show that, in striking contrast to splenectomized normal mice, L2 mice exhibit unchanged frequencies of peritoneal B-1a cells. The IgH repertoire of these B-1a cells, however, was severely perturbed in that the previously described predominant B-1a H chains were no longer present. The repertoire changes were partial since phosphatidylcholine-specific B-1a cells were present in similar numbers before and after splenectomy. Thus, splenic Ags appear to act as "survival factors" for major subsets of peritoneal B cells. The loss of B-1a cells in the absence of such factors is compensated by repertoire changes among B-1a cells in B cell lymphopenic L2 but not normal mice.


Purification, Characterization, and Gene Expression of Rice Endo-β-N-Acetylglucosaminidase, Endo-Os.
In the endoplasmic reticulum-associated degradation system of plant and animal cells, high-mannose type free N-glycans (HMT-FNGs) are produced from misfolded glycoproteins prior to proteasomal degradation, and two enzymes, cytosolic peptide:N-glycanase (cPNGase) and endo-β-N-acetylglucosaminidase (endo-β-GlcNAc-ase), are involved in the deglycosylation. Although the physiological functions of these FNGs in plant growth and development remain to be elucidated, detailed characterization of cPNGase and endo-β-GlcNAc-ase is required. In our previous work, we described the purification, characterization, and subcellular distribution of some plant endo-β-GlcNAc-ases and preliminarily reported the gene information of rice endo-β-GlcNAc-ase (Endo-Os). Furthermore, we analyzed the changes in gene expression of endo-β-GlcNAc-ase during tomato fruit maturation and constructed a mutant line of Arabidopsis thaliana, in which the two endo-β-GlcNAc-ase genes were knocked-out based on the Endo-Os gene. In this report, we describe the purification, characterization, amino acid sequence, and gene cloning of Endo-Os in detail. Purified Endo-Os, with an optimal pH of 6.5, showed high activity for high-mannose type N-glycans bearing the Manα1-2Manα1-3Manβ1 unit; this substrate specificity was almost the same as that of other plant endo-β-GlcNAc-ases, suggesting that Endo-Os plays a critical role in the production of HTM-FNGs in the cytosol. Electrospray ionization-mass spectrometry analysis of the tryptic peptides revealed 17 internal amino acid sequences, including the C terminus; the N-terminal sequence could not be identified due to chemical modification. These internal amino acid sequences were consistent with the amino acid sequence (UniProt ID: Q5W6R1) deduced from the Oryza sativa cDNA clone AK112067 (gene ID: Os05g0346500). Recombinant Endo-Os expressed in Escherichia coli using cDNA showed the same enzymatic properties as those of native Endo-Os.


Recognizing the role of parents in developmental outcomes: a systems approach to evaluating the child with developmental disabilities.
When developmental concerns arise in children, a clinical assessment focuses on the child's developmental profile to achieve three goals (1) determine diagnosis, (2) develop interventions, and (3) evaluate progress. Parents often have needs during this time that are not addressed by professionals because of the exclusive focus on the child during the evaluation. In this article, we suggest that clinicians take a "systems" approach to the assessment process by recognizing how the well being of family members can impact a child with a developmental disability. We review systems theory and its conceptualization of individual functioning and discuss how parental well-being differs according to child diagnosis. Finally we suggest a systems-based model to use during the assessment process.


Ecological gradients drive insect wing loss and speciation: The role of the alpine treeline.
Alpine ecosystems are frequently characterized by an abundance of wing-reduced insect species, but the drivers of this biodiversity remain poorly understood. Insect wing reduction in these environments has variously been attributed to altitude, temperature, isolation, habitat stability or decreased habitat size. We used fine-scale ecotypic and genomic analyses, along with broad-scale distributional analyses of ecotypes, to unravel the ecological drivers of wing reduction in the wing-dimorphic stonefly Zelandoperla fenestrata complex. Altitudinal transects within populations revealed dramatic wing reduction over very fine spatial scales, tightly linked to the alpine treeline. Broad biogeographical analyses confirm that the treeline has a much stronger effect on these ecotype distributions than altitude per se. Molecular analyses revealed parallel genomic divergence between vestigial-winged (high altitude) and full-winged (low altitude) ecotypes across distinct streams. These data thus highlight the role of the alpine treeline as a key driver of rapid speciation, providing a new model for ecological diversification along exposure gradients.


It Starts With Me: Privacy concerns and stigma in the evaluation of a Facebook health promotion intervention.
Background As efforts continue to increase rates of HIV testing and condom use among at-risk communities in England, organisations have sought use social media for health promotion interventions. As part of a wider evaluation of It Starts With Me (ISWM), a sexual health promotion intervention in England targeting gay and bisexual men and African people through Facebook, this study sought to explore how the online environment shapes end user engagement with sexual health interventions. A primary objective was to explore how privacy concerns can act as a barrier to engagement for the audience of ISWM. A purposive sample of 40 individuals were recruited, who were targeted by the intervention for in-depth interviews. Data collection was in two phases. In the first phase, individuals were sampled based on engagement with online health interventions in general, while in the second phase, all individuals were sampled on the basis of engagement with the intervention. Privacy concerns related to the ecology of social networking sites, issues with implied disclosure and discrimination, as well as uncertainty over control of data. These concerns limited the organic reach of the intervention by confining the intervention to those who already held the norms diffused through it, and by discouraging participants from sharing and commenting on content. Care should be taken to address concerns when designing interventions delivered through social media. Gated interventions may be more beneficial for marginalised communities, while large-scale interventions such as ISWM may provide a useful backdrop for face-to-face interventions.


Toxicity profiling of marine surface sediments: A case study using rapid screening bioassays of exhaustive total extracts, elutriates and passive sampler extracts.
This study was carried out in the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea) (Hylland et al., 2015) and aimed (1) to evaluate the toxicity of marine sediments using a battery of rapid toxicity bioassays, and; (2) to explore the applicability and data interpretation of in vitro toxicity profiling of sediment extracts obtained from ex situ passive sampling. Sediment samples were collected at 12 selected (estuarine, coastal, offshore) sites in the North Sea, Icelandic waters (as reference sites), south-western Baltic Sea and western Mediterranean during autumn 2008. Organic extracts using a mild non-destructive clean-up procedure were prepared from total sediment and silicone passive samplers and tested with five in vitro bioassays: DR-Luc bioassay, ER-Luc bioassay, AR-EcoScreen bioassay, transthyretin (TTR) binding assay, and Vibrio fischeri bioluminescence bioassay. In vitro toxicity profiling of total sediment and silicone passive sampler extracts showed the presence of multiple organic contaminations by arylhydrocarbon receptor agonists (e.g. polycyclic aromatic hydrocarbons) and endocrine-active compounds, as well as non-specific toxicity caused by organic contaminants, at virtually all sampling sites. In vitro responses to total sediment extracts from coastal/estuarine sites were significantly different from those in offshore sites (p < 0.05). Several bioassays of passive sampler extracts showed highest activity in some offshore sediment samples. Impact on embryogenesis success and larval growth in undiluted sediment elutriates was shown at some sites using the in vivo sea urchin embryo test. The observed toxicity profiles could only partially be explained by the chemical target analysis, indicating the presence of unknown or unanalysed biologically-active compounds in the sediments. In vitro bioassay testing with silicone passive sampler extracts of sediments is a promising tool to assess the toxic potency of the bioavailable fraction of hydrophobic sediment contaminants, but further work will be needed before it can be routinely applied for sediment quality assessment.


Healthy Life Centre participants' perceptions of living with overweight or obesity and seeking help for a perceived "wrong" lifestyle - a qualitative interview study.
Overweight and obesity are complex conditions, associated with a wide range of serious health issues. In contemporary society, body size is an important part of a person's self-representation. Lifestyle changes are difficult and long-term weight management is associated with a high risk of failure. In primary health care in Norway, lifestyle interventions are offered by Healthy Life Centres (HLCs) to those seeking help with weight management. The aim of this study was to explore HLC participants' experiences of living with overweight or obesity and perceptions of seeking help to change dietary and activity habits. This exploratory study employed a qualitative design. Semi-structured in-depth interviews were conducted with 13 participants. Data were transcribed verbatim and analysed using qualitative content analysis. The analysis resulted in one main theme: Searching for dignity, based on two themes: 1) Needing to justify avoidance of personal responsibility and 2) A desire to change. Changing dietary and activity habits is difficult as the emotional alternation between shame, guilt and pride influences the ability to assume personal responsibility. A deeper understanding of each participant's perceptions and experiences is important for the ability to tailor and provide a high quality health service. Addressing participants' emotional distress and search for dignity is necessary for enabling dietary and activity change. This should be considered in the future development of HLCs and health promotion interventions in order to educate service users about emotions and the role they play in food consumption and inactivity. Weight stigma at individual and system level as well as responsibility related to dilemmas about "right" or "wrong" lifestyle should be addressed.


The gamma-crystallins and human cataracts: a puzzle made clearer.
Despite the fact that cataracts constitute the leading cause of blindness worldwide, the mechanisms of lens opacification remain unclear. We recently mapped the aculeiform cataract to the gamma-crystallin locus (CRYG) on chromosome 2q33-35, and mutational analysis of the CRYG-genes cluster identified the aculeiform-cataract mutation in exon 2 of gamma-crystallin D (CRYGD). This mutation occurred in a highly conserved amino acid and could be associated with an impaired folding of CRYGD. During our study, we observed that the previously reported Coppock-like-cataract mutation, the first human cataract mutation, in the pseudogene CRYGE represented a polymorphism seen in 23% of our control population. Further analysis of the original Coppock-like-cataract family identified a missense mutation in a highly conserved segment of exon 2 of CRYGC. These mutations were not seen in a large control population. There is no direct evidence, to date, that up-regulation of a pseudogene causes cataracts. To our knowledge, these findings are the first evidence of an involvement of CRYGC and support the role of CRYGD in human cataract formation.


Production and use of adeno-associated virus vectors as tools for cancer immunotherapy.
Recombinant adeno-associated viruses (rAAVs) are attractive tools for research in cancer immunotherapy. A single administration of an AAV vector in tumor mouse models induces a progressive increase in transgene expression which reaches a plateau 1 or 2 weeks after administration. The rAAV is then able to maintain the expression of the immunostimulatory transgene. Thus, the use of these vectors obviates the need for frequent administrations of the therapeutic protein to achieve the antitumor effect. The long-term expression of AAV vectors can be exploited for the evaluation of the antitumor activity of immune-enhancing proteins. Most preclinical studies have focused on the expression of cytokines and on the induction of immune responses elicited by tumor-associated antigens expressed by rAAVs. Notwithstanding, rAAVs may not be suitable for immunostimulatory proteins that require high and/or immediate expression. In this chapter, we review a feasible, reliable and detailed protocol to produce and purify AAV vectors as a tool for cancer immunotherapy strategies.


Dissipation behavior and dietary risk assessment of cyclaniliprole and its metabolite in cabbage under field conditions.
Cyclaniliprole, a novel diamide insecticide, can successfully control Spodoptera litura (Fabricius, 1775) in cabbage. Understanding the residual level of cyclaniliprole in crops and the risk related to its dietary intake is imperative for safe application. Here, we established a simplified, sensitive method for simultaneous analysis of cyclaniliprole and its metabolite NK-1375 (3-bromo-2-((2-bromo-4H-pyrazolo[1,5-d]pyrido[3,2-b]-[1,4]oxazin-4-ylidene)amino)-5-chloro-N-(1-cyclopropylethyl)benzamide) in cabbage by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate their dissipation behavior and residual characteristics. Cyclaniliprole showed rapid dissipation in cabbage and had a half-life of 1.8-2.7 days. The highest residue of total cyclaniliprole (sum of cyclaniliprole and NK-1375) in cabbage from different pre-harvest intervals (3 and 5 days) was 0.25 mg/kg. Our results confirmed the generally low dietary risk quotient of cyclaniliprole (0.243-1.036%) among different age and gender groups in China. Therefore, cyclaniliprole did not pose an unacceptable risk to consumers. This study contributes to setting cyclaniliprole maximum residue limit in cabbage by assessing its dissipation fate and food safety risks.


Interface energies in ising spin glasses.
The replica method has been used to calculate the interface free energy associated with the change from periodic to antiperiodic boundary conditions in finite-dimensional spin glasses. At mean-field level the interface free energy vanishes, but after allowing for fluctuation effects, a nonzero interface free energy is obtained which is significantly different from numerical expectations.


[Changes in fine morphological structures of Escherichia coli, Staphylococcus aureus and spores of Bacillus anthracis vaccine strain STI under the action of the disinfectant "Veltolen"].
Changes in fine morphological structures of E. coli, S. aureus and spores of B. anthracis vaccine strain STI under the action of the disinfectant "Veltolen" manufactured by the Closed Joint-Stock Company "Velt", were evaluated. When used at concentrations of 0.0025-0.025%, the preparation induced the loosening of the cell wall in all microorganisms under study, the intensive formation of bubbles on the cell wall surface with their subsequent separation from the cell wall and the formation of "rosettes". In case of more prolonged exposure (up to 60 minutes) and higher concentrations of the preparation these phenomena became more intensive and finally led to the destruction of bacterial cells.


Decreasing propensity to mind-wander with transcranial direct current stimulation.
Mind wandering or task-unrelated thought (TUT) is associated with various impairments as well as with adaptive functions, indicating the importance of regulating this process. Although Axelrod et al. (2015) have shown that anodal/cathodal transcranial direct current stimulation (tDCS) of the left/right lateral prefrontal cortex (LPFC) could increase the propensity for mind wandering, it remains unclear whether a different tDCS protocol could have the reverse effect. The present study investigated whether and how simultaneous stimulation of the left LPFC and right inferior parietal lobule (IPL) could modulate TUTs. These areas may be crucial for regulating both TUTs and its neural underpinning (default mode network). We applied tDCS to the right IPL/left LPFC prior to a perceptually demanding flanker task and compared TUT propensity during the task among tDCS groups. We found that TUT propensity was reduced by anodal/cathodal tDCS of the right IPL/left LPFC compared with cathodal/anodal tDCS, and the results for the sham group were intermediate between these two groups. This is the first study to demonstrate that tDCS can decrease, as well as increase, TUT propensity.


The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis.
Phosphoribosyl-ATP pyrophosphohydrolase is the second enzyme in the histidine-biosynthetic pathway, irreversibly hydrolyzing phosphoribosyl-ATP to phosphoribosyl-AMP and pyrophosphate. It is encoded by the hisE gene, which is present as a separate gene in many bacteria and archaea but is fused to hisI in other bacteria, fungi and plants. Because of its essentiality for growth in vitro, HisE is a potential drug target for tuberculosis. The crystal structures of two native (uncomplexed) forms of HisE from Mycobacterium tuberculosis have been determined to resolutions of 1.25 and 1.79 A. The structure of the apoenzyme reveals that the protein is composed of five alpha-helices with connecting loops and is a member of the alpha-helical nucleoside-triphosphate pyrophosphatase superfamily. The biological unit of the protein is a homodimer, with an active site on each subunit composed of residues exclusively from that subunit. A comparison with the Campylobacter jejuni dUTPase active site allowed the identification of putative metal- and substrate-binding sites in HisE, including four conserved glutamate and glutamine residues in the sequence that are consistent with a motif for pyrophosphohydrolase activity. However, significant differences between family members are observed in the loop region between alpha-helices H1 and H3. The crystal structure of M. tuberculosis HisE provides insights into possible mechanisms of substrate binding and the diversity of the nucleoside-triphosphate pyrophosphatase superfamily.


Changes in mortality trends amongst common diseases during the COVID-19 pandemic in Sweden.
It has been found that COVID-19 increases deaths within common diseases in countries that have implemented strict lockdowns. In order to elucidate the proper national response to a pandemic, the mortality rates within COVID-19 and various diseases need to be studied in countries whose pandemic response differ. Sweden represents a country with lax pandemic restrictions, and we aimed to study the effects of COVID-19 on historical mortality rates within common diseases during 2020. Regression models and moving averages were used to predict expected premature mortality per the ICD-10 during 2020 using historical data sets. Predicted values were then compared to recorded premature mortality to identify changes in mortality trends. Seasonal increased mortality was found within neurological diseases. Infectious diseases, tumours and cardiac disease mortality rates decreased compared to expected outcome. Changes in mortality trends were observed for several common diseases during the COVID-19 pandemic. Neurological and cardiac conditions, infections and tumours are examples of diseases that were heavily affected by the pandemic. The indirect effects of COVID-19 on certain patient populations should be considered when determining pandemic impact.


[Intradural reconstructive surgery of anterior fossa dural lesions using pedunculated periosteal flaps].
The cranio-cerebral injury could result in cerebro-spinal fluid fistula with serious consequences in form of meningitis. In a number of cases a surgical procedure is needed, however in spite of established standards the controversies are still present concerning approach and reconstruction technique. The author presents his own experience in duroplastic operations with intradural use of pedunculated periostal allograft flaps.


Embolization using warmed glue via the triaxial microballoon occlusion system for various vascular disorders.
We aimed to illustrate the benefits of using warmed glue for viscosity reduction via the triaxial microballoon system for the treatment of various vascular disorders. Seven patients who underwent 10 treatment sessions for hemoptysis, type II endoleak, post-pancreatic surgical bleeding, spontaneous retroperitoneal bleeding, or ovarian tumor bleeding were evaluated based on technical and clinical outcomes. In the procedure, the triaxial system, consisting of a 4.5-Fr guiding catheter, a 2.8-Fr microballoon catheter, and a 1.9-Fr no-taper microcatheter, was advanced into the target lesion. Glue (33% n-butyl cyanoacrylate mixed with Lipiodol) warmed to 40°C was injected under balloon occlusion. The common hepatic, right bronchial, intercostals, internal mammary, costocervical, lateral thoracic, superior thoracic, thoracoacromial, inferior thyroid, iliolumbar, lumbar, internal pudendal arteries, and branch of the inferior mesenteric artery were successfully embolized; 100% technical success and 100% clinical success were obtained after each session. Our modified balloon-occluded glue embolization may lead to better handling with more distal glue penetration capability.


Hand and finger replantation after protracted ischemia (more than 24 hours).
Ischemia tolerance has been a major concern during hand and finger replantation. Because of multiple referrals and damage control resuscitation, ischemia is occasionally prolonged for more than 24 hours. Amputation impairs functional efficiency in amputees; therefore, if there is a favorable indication for replantation, microsurgical replantation can be performed to salvage the function of the affected part to an acceptable extent.Between 1998 and 2006, 14 patients underwent 25 replantations after prolonged ischemia of more than 24 hours. Of the 14 patients, 12 were referred to our hospital after unsuccessful replantations and admitted to the emergency room. Two of these patients underwent thumb amputations, and 10 patients underwent multiple digit amputations. Two patients underwent wrist amputation with associated polytrauma and profound shock, both hand replantations were performed on the following day after ICU management with damage control resuscitation was performed to control excessive bleeding and stabilize vital signs.In this study, 16 replantations were successful and 9 failed; thus, the success rate was 64.0%. Several secondary procedures were required for restoring the functional ability of the reconstructed parts.Ischemia time is critical for limb salvage. Hands and fingers have very little muscle tissue. Hence, replantation of these parts can be performed even in the case of prolonged ischemia to restore the hand function.


Absence of Relevant Thermal Conversion of Cannabidiol to Tetrahydrocannabinol in E-Cigarette Vapor and Low-Tetrahydrocannabinol Cannabis Smoke.
Introduction: Recent research claimed that CBD in commercial electronic cigarette (e-cigarette) liquids can be converted into psychotropic amounts of Δ9-THC. This study aims to validate this claim using a realistic e-cigarette setup. In addition, this study also investigates if such a conversion may occur during smoking of CBD-rich cannabis joints. Materials and Methods: Two different CBD liquids were vaporized using two different e-cigarette models, one of which was operated at extreme energy settings (0.2 Ω and 200 W). The smoke of six CBD joints was collected using a rotary smoking machine according to ISO 4387:2019. Analyses were conducted using nuclear magnetic resonance spectrometry as well as liquid chromatography tandem mass spectrometry. Results: For the condensed e-cigarette liquids, no increase in THC concentration could be observed. For the CBD joints, no THC formation was provable. The recovered THC concentrations were ranging between 1% and 48% (0.034 and 0.73 mg) of the THC amount initially contained in the joints before smoking. Conclusions: Using realistic conditions of consumer exposure, relevant conversion of CBD to THC appears to not be occurring. The health risk of CBD liquids for e-cigarettes, as well as low-THC cannabis intended for smoking, can be assessed by concentrations in the source material without the need to consider significant changes in psychotropic compounds during use by consumers.


The pharmacokinetics and pharmacodynamics of the carbapanemes: focus on doripenem.
Carbapenems are the most potent group of beta-lactam agents, having a broad spectrum of bactericidal activity against both Gram-negative and Gram-positive bacteria including anaerobes. Doripenem is a new carbapenem endowed with excellent bactericidal activity, a wide spectrum of antibacterial activity against difficult nosocomial pathogens, including extended-spectrum beta-lactamase producers. Its high stability in solution render it extremely flexible for dosing and infusion time. It is the only carbapenem which has been registered officially for administration as an extended infusion of more than 4 hours, which can thus enhance its potential clinical efficacy against difficult bacterial pathogens with MICs of 4-8 mg/L.


Living amidst large wildlife: livestock and crop depredation by large mammals in the interior villages of Bhadra Tiger Reserve, South India.
Conflict with humans over livestock and crops seriously undermines the conservation prospects of India's large and potentially dangerous mammals such as the tiger (Panthera tigris) and elephant (Elephas maximus). This study, carried out in Bhadra Tiger Reserve in south India, estimates the extent of material and monetary loss incurred by resident villagers between 1996 and 1999 in conflicts with large felines and elephants, describes the spatiotemporal patterns of animal damage, and evaluates the success of compensation schemes that have formed the mainstay of loss-alleviation measures. Annually each household lost an estimated 12% (0.9 head) of their total holding to large felines, and approximately 11% of their annual grain production (0.82 tonnes per family) to elephants. Compensations awarded offset only 5% of the livestock loss and 14% of crop losses and were accompanied by protracted delays in the processing of claims. Although the compensation scheme has largely failed to achieve its objective of alleviating loss, its implementation requires urgent improvement if reprisal against large wild mammals is to be minimized. Furthermore, innovative schemes of livestock and crop insurance need to be tested as alternatives to compensations.


Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment.
Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 microg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 microg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma concentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary.


Outcome of adenotonsillectomy for severe obstructive sleep apnea in children.
To study changes in sleep behavior and quality of life in children after adenotonsillectomy for severe obstructive sleep apnea identified by a respiratory distress index > or = 30. Children enrolled in the study underwent adenotonsillectomy and had both pre- and post-operative polysomnography. Caregivers also completed an OSA-18 quality of life survey prior to polysomnography and within 6 months of surgery. Paired Student's t-tests were used to compare pre- and post-operative scores. The study population included 29 children. The mean age was 7.1 years (range 1.4-17.0). The most common comorbidities were obesity, asthma and allergic disease. The mean pre-operative RDI was 63.9 and the mean post-operative RDI was 14.2 (P < .0001). The mean total OSA-18 score before surgery was 77.6 and after surgery was 33.2. The differences in pre- and post-operative OSA-18 total scores and domain scores were significant (P < .0001). Children with severe OSA who undergo adenotonsillectomy show a significant improvement in RDI and in quality of life over a period of several months after surgery. However, OSA does not resolve in the majority of these children and post-operative PSG is recommended to identify those who may require additional therapy.


Frequency response of vestibular reflexes in neck, back, and lower limb muscles.
Vestibular pathways form short-latency disynaptic connections with neck motoneurons, whereas they form longer-latency disynaptic and polysynaptic connections with lower limb motoneurons. We quantified frequency responses of vestibular reflexes in neck, back, and lower limb muscles to explain between-muscle differences. Two hypotheses were evaluated: 1) that muscle-specific motor-unit properties influence the bandwidth of vestibular reflexes; and 2) that frequency responses of vestibular reflexes differ between neck, back, and lower limb muscles because of neural filtering. Subjects were exposed to electrical vestibular stimuli over bandwidths of 0-25 and 0-75 Hz while recording activity in sternocleidomastoid, splenius capitis, erector spinae, soleus, and medial gastrocnemius muscles. Coherence between stimulus and muscle activity revealed markedly larger vestibular reflex bandwidths in neck muscles (0-70 Hz) than back (0-15 Hz) or lower limb muscles (0-20 Hz). In addition, vestibular reflexes in back and lower limb muscles undergo low-pass filtering compared with neck-muscle responses, which span a broader dynamic range. These results suggest that the wider bandwidth of head-neck biomechanics requires a vestibular influence on neck-muscle activation across a larger dynamic range than lower limb muscles. A computational model of vestibular afferents and a motoneuron pool indicates that motor-unit properties are not primary contributors to the bandwidth filtering of vestibular reflexes in different muscles. Instead, our experimental findings suggest that pathway-dependent neural filtering, not captured in our model, contributes to these muscle-specific responses. Furthermore, gain-phase discontinuities in the neck-muscle vestibular reflexes provide evidence of destructive interaction between different reflex components, likely via indirect vestibular-motor pathways.


[Epistemic injustice during the medical education process in the hospital context].
The educational model adopted by the Universidad Nacional Autónoma de México (UNAM) Faculty of Medicine is constructivist; it is a model based on competence development. It aims to provide learning environments that incorporate real activities (it helps the students to develop social negotiation skills, as part of their integral learning; it encourages them to take a critical and reflexive approach; and it is also a student-centered model). However, many challenges arise when this model is implemented in the context of hospital environments. Therefore, our aim was to analyse the hospital as an hermeneutical community and as a power relations scenario, contrary to the constructivist model. In the analysis of a conflict between a chief of a medical department and an undergraduated medical intern, we use Miranda Fricker's categories discriminatory epistemic injustice, and testimonial injustice, as well as Foucault's power relationships and knowledge. The program implementation is placed in the context of power relations and different disciplinary methods that could affect the training process of the students, whose educational background belongs to the constructivist model. This in part is due to the existence of informal normative structures that are hidden in the process of medical knowledge construction at the hospital scenario. Practices of epistemic discriminatory injustice in the hospital environment increase vulnerability conditions for medical students in their education process.


The global Filipino nurse: An integrative review of Filipino nurses' work experiences.
To understand the work-related experiences of Philippine-trained nurses working globally. The Philippines is a major source country of foreign-trained nurses located globally. However, there is paucity of research on professional factors and career related issues affecting foreign-trained nurses' work experiences. An integrative review through a comprehensive search of literature was undertaken from November 2015 and was repeated in August 2016. Seven articles satisfied the selection criteria. Filipino nurses experienced differences in the practice of nursing in terms of work process, roles and autonomy. Moreover, they encountered challenges such as work-related discrimination and technical difficulties within the organisation. A clear understanding of Filipino nurses' work experiences and the challenges they have encountered suggests identification of important constructs influencing effective translation of nursing practice across cultures and health systems, which then form the basis for support strategies. It is critical to recognize foreign-trained nurses' experience of work-related differences and challenges as these foster favorable conditions for the management team to plan and continually evaluate policies around recruitment, retention and support offered to these nurses. Furthermore, findings suggest internationalization of nursing framework and standards integrating a transcultural paradigm among staff members within a work organisation.


Leisure time physical activity in middle age predicts the metabolic syndrome in old age: results of a 28-year follow-up of men in the Oslo study.
Data are scarce on the long term relationship between leisure time physical activity, smoking and development of metabolic syndrome and diabetes. We wanted to investigate the relationship between leisure time physical activity and smoking measured in middle age and the occurrence of the metabolic syndrome and diabetes in men that participated in two cardiovascular screenings of the Oslo Study 28 years apart. Men residing in Oslo and born in 1923-32 (n = 16 209) were screened for cardiovascular diseases and risk factors in 1972/3. Of the original cohort, those who also lived in same area in 2000 were invited to a repeat screening examination, attended by 6 410 men. The metabolic syndrome was defined according to a modification of the National Cholesterol Education Program criteria. Leisure time physical activity, smoking, educational attendance and the presence of diabetes were self-reported. Leisure time physical activity decreased between the first and second screening and tracked only moderately between the two time points (Spearman's rho = 0.25). Leisure time physical activity adjusted for age and educational attendance was a significant predictor of both the metabolic syndrome and diabetes in 2000 (odds ratio for moderately vigorous versus sedentary/light activity was 0.65 [95% CI, 0.54-0.80] for the metabolic syndrome and 0.68 [0.52-0.91] for diabetes) (test for trend P < 0.05). However, when adjusted for more factors measured in 1972/3 including glucose, triglycerides, body mass index, treated hypertension and systolic blood pressure these associations were markedly attenuated. Smoking was associated with the metabolic syndrome but not with diabetes in 2000. Physical activity during leisure recorded in middle age prior to the current waves of obesity and diabetes had an independent predictive association with the presence of the metabolic syndrome but not significantly so with diabetes 28 years later in life, when the subjects were elderly.


MEDCAPS--do they work?
The objectives of this paper are to lay out for wider discussion the potential advantages and disadvantages of active military units providing medical care for the local population through ad hoc clinics (MEDCAPS). The literature on this subject has been reviewed and the personal experience of MEDCAPS by the author and other doctors in Helmand Province 2007/8 is presented. Although in the published literature, MEDCAPS are almost universally regarded as being good for relations between the military and civilians, the reality on the ground is that they potentially risk the lives of both staff and patients. and may actually contribute little in terms of relieving suffering, or improving relations between military and civilians. The conclusion of this paper is that MEDCAPs at best have a very limited and specific role, but that there will remain a strong desire from staff on the ground to initiate them.


Improving Walking, Muscle Strength, and Balance in the Elderly with an Exergame Using Kinect: A Randomized Controlled Trial.
Many issues prevent elderly individuals from exercising in daily life. There is a need for a system that allows elderly individuals to engage in exercise regularly at a low cost. We developed an exergame that uses a Kinect(®) sensor (Microsoft Corp., Redmond, WA) and conducted a randomized controlled trial of the effects of using this exergame on muscle strength and balance in healthy elderly individuals. We enrolled 57 healthy elderly individuals and randomly divided them into an intervention group (n=29) and a control group (n=28) using a table of random numbers. All participants underwent gait analyses and were examined using the Berg Balance Scale (BBS), Functional Reach Test (FRT), and the 30-second chair-stand (CS-30) test before the intervention. Participants in the intervention group played the exergame once or twice a week, up to a total of 24 times. The tests were repeated after intervention, and the scores were compared with those obtained before intervention. Our results indicated that walking, muscle strength, and motor function improved in participants in the intervention group. Decreased double standing time (P=0.03), minimum foot clearance (P=0.04), BBS scores (P<0.01), CS-30 scores (P<0.01), and FRT scores (P<0.01) significantly improved in the intervention group compared with values in the control group. The Kinect-based exergame developed in this study was found to be effective in improving walking, muscular strength, and balance in elderly people.


Nano-inspired smart interfaces: fluidic interactivity and its impact on heat transfer.
Interface-inspired convection is a key heat transfer scheme for hot spot cooling and thermal energy transfer. An unavoidable trade-off of the convective heat transfer is pressure loss caused by fluidic resistance on an interface. To overcome this limitation, we uncover that nano-inspired interfaces can trigger a peculiar fluidic interactivity, which can pursue all the two sides of the coin: heat transfer and fluidic friction. We demonstrate the validity of a quasi-fin effect of Si-based nanostructures based on conductive capability of heat dissipation valid under the interactivity with fluidic viscous sublayer. The exclusive fluid-interface friction is achieved when the height of the nanostructures is much less than the thickness of the viscous sublayers in the turbulent regime. The strategic nanostructures show an enhancement of heat transfer coefficients in the wall jet region by more than 21% without any significant macroscale pressure loss under single-phase impinging jet. Nanostructures guaranteeing fluid access via an equivalent vacancy larger than the diffusive path length of viscid flow lead to local heat transfer enhancement of more than 13% at a stagnation point. Functional nanostructures will give shape to possible breakthroughs in heat transfer and its optimization can be pursued for engineered systems.


Electrokinetic focusing of SARS-CoV-2 spike protein via ion concentration polarization in a paper-based lateral flow assay.
The COVID-19 pandemic highlighted the importance of designing sensitive and selective point-of-care (POC) diagnostic sensors for early and rapid detection of infection. Paper-based lateral flow assays (LFAs) are easy to use, inexpensive, and rapid, but they lack sensitivity. Preconcentration techniques can improve the sensitivity of LFAs by increasing the local concentration of the analyte before detection. Here, ion concentration polarization (ICP) is used to focus the analyte, SARS-CoV-2 Spike protein (S-protein), directly over a test line composed of angiotensin converting enzyme 2 (ACE2) capture probes. ICP is the enrichment and depletion of electrolyte ions at opposing ends of an ion-selective membrane under a voltage bias. The ion depleted zone (IDZ) establishes a steep gradient in electric field strength along its boundary. Enrichment of charged species (such as a biomolecule analyte) occurs at an axial location along this electric field gradient in the presence of a fluid flow that counteracts migration of those species - a phenomenon called ICP focusing. In this paper, running buffer composition and pretreatment solutions for ICP focusing in a paper-based LFA are evaluated, and the method of voltage application for ICP-enrichment is optimized. With a power consumption of 1.8 mW, S-protein is concentrated by a factor of 21-fold, leading to a 2.9-fold increase in the signal from the LFA compared to a LFA without ICP-enrichment. The described ICP-enhanced LFA is significant because the preconcentration strategy is amenable to POC applications and can be applied to existing LFAs for improvement in sensitivity.


Impact of Dimensionality Reduction on Outlier Detection: an Empirical Study.
Outlier detection is a fundamental data analytics technique often used for many security applications. Numerous outlier detection techniques exist, and in most cases are used to directly identify outliers without any interaction. Typically the underlying data used is often high dimensional and complex. Even though outliers may be identified, since humans can easily grasp low dimensional spaces, it is difficult for a security expert to understand/visualize why a particular event or record has been identified as an outlier. In this paper we study the extent to which outlier detection techniques work in smaller dimensions and how well dimensional reduction techniques still enable accurate detection of outliers. This can help us to understand the extent to which data can be visualized while still retaining the intrinsic outlyingness of the outliers.


Irreversible effects of dichloromethane on the brain after long term exposure: a quantitative study of DNA and the glial cell marker proteins S-100 and GFA.
Two astroglial proteins S-100 and GFA, as well as DNA, were quantitatively determined in different regions of the gerbil brain after continuous long term exposure to moderate concentrations of dichloromethane. The intention of the experiment was to expose three groups of animals at three different solvent concentrations (210, 350, or 700 ppm) for three months. Because of the high mortality rate, however, the 700 ppm experiment was terminated after seven weeks. In the 350 ppm experiment half the exposed animals died and the exposure period was terminated after ten weeks. After the exposure period, the surviving gerbils in the 350 ppm exposure group and those from the 210 ppm group were allowed a postexposure solvent free period of four months. After exposure to 350 ppm, increased concentrations of the two astroglial proteins were found in the frontal and sensory motor cerebral cortex, compatible with astrogliosis in these regions. Exposure to 350 ppm and 210 ppm decreased the concentrations of DNA in the hippocampus. Moreover, after exposure at 350 ppm, DNA concentrations were also decreased in the cerebellar hemispheres. These results indicate a decreased cell density in these brain regions, probably due to cell loss. The neurotoxic effects were not found to correlate with the endogenous formation of carbon monoxide.


Genetic differences in metabolism of benzo(a)pyrene in cultured epidermal and dermal cells of responsive and nonresponsive mice.
Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydroxylase (AHH) activity. Primary cultures of epidermal and dermal cells isolated from newborn mice were treated with benz(a)anthracene for 24 hr. In both types of cells, AHH activity was induced in all four strains of mice, irrespective of their responsiveness in vivo. In the epidermal cells, basal AHH activity varied within a relatively small range of 4.6 to 8.8 pmol per mg protein per hr, and the activity was increased 4.4 to 8.7 times by benz(a)anthracene treatment. There was no difference in the extent of the induction in different strains of mice. In dermal cells, the basal level of AHH activity was in the range of 3.6 to 9.1 pmol per mg protein per hr, and benz(a)anthracene treatment induced AHH, but to various degrees depending on the responsiveness in vivo. Epidermal cells of the responsive mice metabolized more than 90% of the added BP in 48 hr, while those of nonresponsive mice metabolized only 60 to 70%. Dermal cells also metabolized BP, but to a lesser extent than did epidermal cells, and there was no strain difference in its metabolism. Time-course studies revealed that epidermal cells of responsive mice metabolized BP more rapidly than did those of nonresponsive mice. The activities of epidermal and dermal cells to metabolize BP were further demonstrated by a cell-mediated mutation assay. Consistent with the results of time-course analysis of the metabolites, shorter treatments with BP (less than 24 hr) showed a clear difference in BP metabolism associated with responsiveness.


Light-harvesting superstructures of green plant chloroplasts lacking photosystems.
The light-harvesting antenna of higher plant photosystem II (LHCII) is the major photosynthetic membrane component encoded by an entire family of homologous nuclear genes. On the contrary, the great majority of proteins of photosystems and electron transport components are encoded by the chloroplast genome. In this work, we succeeded in gradually inhibiting the expression of the chloroplast genes that led to the disappearance of the photosystem complexes, mimicking almost total photoinhibition. The treated plants, despite displaying only some early signs of senescence, sustained their metabolism and growth for several weeks. The only major remaining membrane component was LHCII antenna that formed superstructures - stacks of dozens of thylakoids or supergrana. Freeze-fracture electron microscopy revealed specific organization, directly displaying frequently bifurcated membranes with reduced or totally absent photosystem II (PSII) reaction centre complexes. Our findings show that it is possible to accumulate large amounts of light-harvesting membranes, organized into three-dimensional structures, in the absence of reaction centre complexes. This points to the reciprocal role of LHCII and PSII in self-assembly of the three-dimensional matrix of the photosynthetic membrane, dictating its size and flexible adaptation to the light environment.


The Latin American treatment and innovation network in mental health h (LATINMH): rationale and scope.
Over the past 60 years Latin American countries have been experiencing noticeable demographic and socioeconomic changes, with marked impact on the population health in the region. There is growing recognition of the co-morbidity among mental and physical health problems impacting heavily on health care systems. These challenges open many opportunities for transformational change in the expanding field of global mental health. Given the growing evidence for the wide applicability and efficacy of specific components included in mental health treatment packages, research should focus more on improving the organization and efficiency with which we deliver these specific treatment components already proven to be efficacious. The Latin American Treatment and Innovation Network in Mental Health (LATIN-MH) is a research and training Hub based in Sao Paulo, Brazil, and Lima, Peru. It aims to address the co-morbidity between physical and mental chronic diseases, exploring the opportunity to use technology to support the treatment of these conditions. LATIN-MH strives to move beyond specific single-disease approaches and research silos, whilst maximizing the opportunities to work collaboratively with various groups in the Latin American region, thus contributing to fostering research and building capacity in mental health research. Mental Health, Chronic Disease, mHealth, Capacity Building (MeSH) Key concepts: Chronic diseases have now become the major determinants of the disease burden in Latin America, whereas psychiatric disorders accounted for almost one-third of years lived with disability worldwide in 2005. LATIN-MH is a research and training hub that aims to address the co-morbidity between physical and mental chronic diseases using technology to support their treatments. LATIN-MH strives to move beyond specific single-disease approaches and research siloes, whilst maximizing the opportunities to work collaboratively with various groups in the Latin American region, thus contributing to foster research and build capacity in mental health research. LATIN-MH is built on three driving principles: (i) building capacities to ensure sustainability and autonomy of mental health services, (ii) developing strategic interdisciplinary partnerships, and (iii) integrating mental health treatment into primary care and community health systems.


Effect of maternal diet during lactation on development of bovine insulin-binding antibodies in children at risk for allergy.
The role of exposure to dietary antigens through maternal milk is intriguing, because it may result either in immunization or in tolerance. Exposure to cow's milk proteins results in antibody formation against bovine insulin in infants at risk for type 1 diabetes. To study the appearance of IgG antibodies to bovine and human insulin in infants with an atopic family history whose mothers followed a cow's milk-free diet during the first 3 months of lactation. In a prospective cohort study on prevention of food allergies, 123 infants were exclusively breast-fed or received supplementation with a hydrolyzed casein-based formula (Nutramigen) until the age of 6 months. The mothers either avoided cow's milk during the first 3 months of lactation (diet group) or had an unrestricted diet (nondiet group). The levels of IgG antibodies to bovine and human insulin were determined by enzyme immunoassay at 3, 6, 12, and 18 months and at 4 years. In addition, cord blood was obtained at birth and a maternal sample at delivery. At 3 months, IgG antibodies to bovine insulin were low in both dietary groups (median levels 0.150 and 0. 114 optical density units in the diet and nondiet groups). After exposure to dietary insulin, IgG antibodies to bovine insulin increased in both groups, reaching a peak at 12 months in the nondiet group and at 18 months in the diet group. At 18 months, IgG antibodies to bovine insulin were lower in infants in the nondiet group than in infants in the diet group (0.287 vs 0.500, P<.0001). At 4 years, the antibodies no longer differed between the groups. The exposure to cow's milk proteins through breast milk during the first 3 months of life resulted in decreased levels of antibodies to dietary bovine insulin at 18 months of age, suggesting a role for breast milk antigens in early tolerance induction.