Total Sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute Modulated Bile Acid Metabolism and Intestinal Microbiota Composition in Rats.
In this study, the impact of sn-2 palmitic triacyclglycerols (TAGs) in combination with their ratio of two major TAGs (1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO)) in human milk fat substitute (HMFS) on bile acid (BA) metabolism and intestinal microbiota composition was investigated in newly-weaned Sprague-Dawley rats after four weeks of high-fat feeding. Compared to those of control group rats, HMFS-fed rats had significantly increased contents of six hepatic primary BAs (CDCA, αMCA, βMCA, TCDCA, TαMCA and TβMCA), four ileal primary BAs (UDCA, TCA, TCDCA and TUDCA) and three secondary BAs (DCA, LCA and ωMCA), especially for the HMFS with the highest sn-2 palmitic acid TAGs of 57.9% and OPL to OPO ratio of 1.4. Meanwhile, the inhibition of ileal FXR-FGF15 and activation of TGR5-GLP-1 signaling pathways in HMFS-fed rats were accompanied by the increased levels of enzymes involved in BA synthesis (CYP7A1, CYP27A1 and CYP7B1) in the liver and two key thermogenic proteins (PGC1α and UCP1) in perirenal adipose tissue, respectively. Moreover, increasing sn-2 palmitic TAGs and OPL to OPO ratio in HMFS also altered the microbiota composition both on the phylum and genus level in rats, predominantly microbes associated with bile-salt hydrolase activity, short-chain fatty acid production and reduced obesity risk, which suggested a beneficial effect on host microbial ecosystem. These observations provided important nutritional evidence for developing new HMFS products for infants.


Parasitic Infections in Pregnancy Decrease Placental Transfer of Antipneumococcus Antibodies.
Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on placental antibody transfer. To investigate this, we selected from a parent study of 576 pregnant Kenyan women four groups of women with term deliveries (≥37 weeks), including uninfected women (n = 30) and women with solo infections with malaria (n = 30), hookworm (n = 30), or schistosomiasis (n = 10). Maternal plasma at delivery and infant cord blood were tested via multiplex fluorescent bead assay for IgG against 10 pneumococcal serotypes (PnPs 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F), diphtheria toxoid, and Haemophilus influenzae type B. Infants born to mothers with prenatal malaria, hookworm, or Schistosoma haematobium infections were associated with a significantly reduced ratio of maternal to infant cord blood antibody concentration for Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, and 18C compared to infants of uninfected mothers. Anti-diphtheria toxoid and anti-H. influenzae type B IgG ratios were not significantly different among infection groups. Prenatal parasitic infections decrease the transfer of maternal IgG antibodies to infants for several serotypes of S. pneumoniae.


Faculty support for nurse preceptors.
Preceptored clinical experiences are much valued by nurse educators as a means of exposing students to the expertise of practising nurses; however, with increasingly stressful work situations, preceptoring nurses need faculty support to fulfill their roles in a satisfying and effective way. The author reports on a qualitative study that examined preceptors' views of faculty roles in preceptored clinical experiences and details preceptors' expectations of faculty support. Five main themes were identified. Preceptors stressed the following important faculty functions: (1) accessibility, (2) information provision, (3) evaluation of student performance, (4) advocacy for precepted students, and (5) mentor to preceptors, especially for nurses who are prepared at the diploma level or who lack experience in preceptoring. Various preceptors indicated differences in their needs for faculty assistance in each function, but all functions were confirmed as necessary to the effective functioning of a preceptored learning experience for students. All preceptors confirmed their expectation of active faculty involvement in the preceptored experience.


Defining the minimal length of sequence homology required for selective gene isolation by TAR cloning.
The transformation-associated recombination (TAR) cloning technique allows selective and accurate isolation of chromosomal regions and genes from complex genomes. The technique is based on in vivo recombination between genomic DNA and a linearized vector containing homologous sequences, or hooks, to the gene of interest. The recombination occurs during transformation of yeast spheroplasts that results in the generation of a yeast artificial chromosome (YAC) containing the gene of interest. To further enhance and refine the TAR cloning technology, we determined the minimal size of a specific hook required for gene isolation utilizing the Tg.AC mouse transgene as a targeted region. For this purpose a set of vectors containing a B1 repeat hook and a Tg.AC-specific hook of variable sizes (from 20 to 800 bp) was constructed and checked for efficiency of transgene isolation by a radial TAR cloning. When vectors with a specific hook that was >/=60 bp were utilized, approximately 2% of transformants contained circular YACs with the Tg.AC transgene sequences. Efficiency of cloning dramatically decreased when the TAR vector contained a hook of 40 bp or less. Thus, the minimal length of a unique sequence required for gene isolation by TAR is approximately 60 bp. No transgene-positive YAC clones were detected when an ARS element was incorporated into a vector, demonstrating that the absence of a yeast origin of replication in a vector is a prerequisite for efficient gene isolation by TAR cloning.


A Design Methodology for Medical Processes.
Healthcare processes, especially those belonging to the clinical domain, are acknowledged as complex and characterized by the dynamic nature of the diagnosis, the variability of the decisions made by experts driven by their experiences, the local constraints, the patient's needs, the uncertainty of the patient's response, and the indeterminacy of patient's compliance to treatment. Also, the multiple actors involved in patient's care need clear and transparent communication to ensure care coordination. In this paper, we propose a methodology to model healthcare processes in order to break out complexity and provide transparency. The model is grounded on a set of requirements that make the healthcare domain unique with respect to other knowledge domains. The modeling methodology is based on three main phases: the study of the environmental context, the conceptual modeling, and the logical modeling. The proposed methodology was validated by applying it to the case study of the rehabilitation process of stroke patients in the specific setting of a specialized rehabilitation center. The resulting model was used to define the specifications of a software artifact for the digital administration and collection of assessment tests that was also implemented. Despite being only an example, our case study showed the ability of process modeling to answer the actual needs in healthcare practices. Independently from the medical domain in which the modeling effort is done, the proposed methodology is useful to create high-quality models, and to detect and take into account relevant and tricky situations that can occur during process execution.


[The gift of breast feeding--the practice of breast feeding in Israel].
Breast milk is the optimal food for infant growth and development, the prevention of infectious diseases and mother-child bonding. From the economic perspective, breastfeeding is cost-effective both for the family and society as a whole. The Israeli Ministry of Health encourages breastfeeding as the exclusive source of nutrition for infants in the first 4-6 months of life, with gradual addition of complementary foods thereafter. The promotion of breastfeeding in Israel requires comprehensive national activity with involvement of all the stakeholders. This includes implementation of the International Code of Marketing of Breast Milk Substitutes and joining the international "Baby Friendly Hospitals" project. Knowledge of breastfeeding should be spread, health professionals should be encouraged to become agents of change, support by breast counselors should be encouraged, post-delivery vacations from work should be prolonged and empowerment of women implemented.


People use both heterogeneity and minority representation to evaluate diversity.
The term "diversity," although widely used, can mean different things. Diversity can refer to heterogeneity, i.e., the distribution of people across groups, or to the representation of specific minority groups. We use a conjoint experiment with a race-balanced, national sample to uncover which properties, heterogeneity or minority representation, Americans use to evaluate the extent of racial diversity a neighborhood and whether this assessment varies by participants' race. We show that perceived diversity is strongly associated with heterogeneity. This association is stronger for Whites than for Blacks, Latinos, or Asians. In addition, Blacks, Latinos, and Asians view neighborhoods where their own group is largest as more diverse. Whites vary in their tendency to associate diversity with representation, and Whites who report conservative stances on diversity-related policy issues view predominately White neighborhoods as more diverse than predominately Black neighborhoods. People can agree that diversity is desirable while disagreeing on what makes a community diverse.


[Morphofunctional criteria for the selection of patients with ischemic heart disease and associated arterial hypertension for surgical treatment].
After examination of 255 patients with ischemic heart disease (IHD) and concomitant arterial hypertension (AH) two groups were distinguished according the level of arterial pressure. Group 1 was formed of 89 patients (arterial pressure below 180/80 mm Hg), group 2--of 166 patients (arterial pressure above 180/100 mm Hg). Survival was determined according to certain morphofunctional indices (total affection of coronary arteries, left ventricular output fraction, left ventricular end diastolic pressure, tolerance to physical effort) in nonoperated on and operated on patients suffering from IHD and concomitant AH. It was found that the operation affects positively the "quality" of life more than the survival.


Avascular necrosis of the femoral head in HIV infected patients.
Avascular necrosis (AVN) of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.


Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires.
Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area. Genetic, cellular, and tissue engineering therapies are promising avenues but require days/months for permitting proper functional tissue regeneration. Here we engineered biocompatible silicon carbide semiconductive nanowires that synthetically couple, via membrane nanobridge formations, isolated beating cardiomyocytes over distance, restoring physiological cell-cell conductance, thereby permitting the synchronization of bioelectrical activity in otherwise uncoupled cells. Local in-situ multiple injections of nanowires in the left ventricular infarcted regions allow rapid reinstatement of impulse propagation across damaged areas and recover electrogram parameters and conduction velocity. Here we propose this nanomedical intervention as a strategy for reducing ventricular arrhythmia after acute myocardial infarction.


USP35 regulates mitotic progression by modulating the stability of Aurora B.
Although approximately 100 deubiquitinating enzymes (DUBs) are encoded in the human genome, very little is known about the DUBs that function in mitosis. Here, we demonstrate that DUB USP35 functions as a mitotic regulator by controlling the protein levels and downstream signaling of Aurora B and the depletion of USP35 eventually leads to several mitotic defects including cytokinesis failures. USP35 binds to and deubiquitinates Aurora B, and inhibits the APCCDH1-mediated proteasomal degradation of Aurora B, thus maintaining its steady-state levels during mitosis. In addition, the loss of USP35 decreases the phosphorylation of histone H3-Ser10, an Aurora B substrate. Finally, the transcription factor FoxM1 promotes the expression of USP35, as well as that of Aurora B, during the cell cycle. Our findings suggest that USP35 regulates the stability and function of Aurora B by blocking APCCDH1-induced proteasomal degradation, thereby controlling mitotic progression.


Tolerance of NK cells encountering their viral ligand during development.
During development, T and B cells encountering their cognate ligands via antigen-specific receptors are deleted or rendered anergic. Like T and B cells, natural killer (NK) cells express certain receptors, such as Ly49H, associated with immunoreceptor tyrosine-based activation motif-bearing adaptor proteins that transmit activating signals through Syk family kinases. Ly49H binds with high affinity to a mouse cytomegalovirus (MCMV)-encoded glycoprotein, m157, but does not recognize self-antigens. For comparison with the behavior of immature T and B cells exposed to foreign antigens, we addressed the fate of Ly49H(+) NK cells that encountered their viral ligand during development by retroviral transduction of bone marrow stem cells with m157. In chimeric mice expressing m157, we observed a reduction in Ly49H(+) NK cells in multiple tissues and less Ly49H on the cell surface. NK cells exposed to m157 during development appeared less mature, produced less interferon gamma when stimulated through Ly49H, and were unable to kill m157-bearing target cells. After MCMV infection, these NK cells were severely impaired in their ability to proliferate. Thus, if immature NK cells encounter ligands for their activating receptors, regulatory mechanisms exist to keep these cells in an unresponsive state.


Optimism, coping, and health: assessment and implications of generalized outcome expectancies.
This article describes a scale measuring dispositional optimism, defined in terms of generalized outcome expectancies. Two preliminary studies assessed the scale's psychometric properties and its relationships with several other instruments. The scale was then used in a longitudinal study of symptom reporting among a group of undergraduates. Specifically, respondents were asked to complete three questionnaires 4 weeks before the end of a semester. Included in the questionnaire battery was the measure of optimism, a measure of private self-consciousness, and a 39-item physical symptom checklist. Subjects completed the same set of questionnaires again on the last day of class. Consistent with predictions, subjects who initially reported being highly optimistic were subsequently less likely to report being bothered by symptoms (even after correcting for initial symptom-report levels) than were subjects who initially reported being less optimistic. This effect tended to be stronger among persons high in private self-consciousness than among those lower in private self-consciousness. Discussion centers on other health related applications of the optimism scale, and the relationships between our theoretical orientation and several related theories.


Effects of Resistance Training with Blood Flow Restriction on Explosive Power of Lower Limbs: A Systematic Review and Meta-Analysis.
The purpose of this systematic review and meta-analysis was to compare changes in explosive power between blood flow restriction training and traditional resistance training protocols. Searches of PubMed, Scopus, Web of Science, and OVID Medline were conducted for studies. Inclusion criteria were: (a) healthy people; (b) randomized controlled or controlled trials; (c) outcome measures of explosive performance (peak power, rate of force development, jump performance, sprint performance, etc.); (d) involving a comparison between blood flow restriction training and traditional resistance training. Quality assessment was conducted using the Physiotherapy Evidence Database (PEDro) scale. A total of 12 studies (262 subjects) were finally included for analysis. The PEDro scale score had a median of 5 of 10 points (range: 3-6 points). Significant small to moderate improvements were observed in blood flow restriction training [jump: standard mean difference (SMD) of 0.36 (95% CI: 0.02; 0.69); sprint: SMD of 0.54 (95% CI: 0.00; 1.07); power: SMD of 0.72 (95% CI: 0.17; 1.27)] when compared to traditional resistance training. The findings indicate that blood flow restriction training is more effective in improving explosive power of lower limbs compared to traditional resistance training in healthy people. In addition, blood flow restriction with a wide cuff (≥ 10 cm) during training improved explosive power better than with a narrow cuff or during the rest interval. Blood flow restriction training is very suitable for athletes in short competitive seasons and those who are not able to tolerate high loads (i.e., rehabilitators and the elderly).


The challenging interplay between rheumatoid arthritis, ageing and comorbidities.
The incidence of rheumatoid arthritis (RA) is expected to increase over the next 10 years in the European Union because of the increasing proportion of elderly people. As both RA and ageing are associated with emerging comorbidities such as cardiovascular disease, malignancies and osteoporosis, these factors will have a profound effect on the management of RA. In addition, both increasing age and comorbidities may independently alter commonly used RA-specific outcome measures. Age-related decline in immune cell functions (immunosenescence), such as a decrease in T-cell function, may contribute to the development of RA, as well as comorbidity. The chronic immune stimulation that occurs in RA may also lead to premature ageing and comorbidity. The interplay between RA, ageing and (emerging) comorbidities is interesting but complex. Cardiovascular disease, lung disease, malignancies, bone and muscle wasting and neuropsychiatric disease all occur more frequently in RA patients as compared to the general population. It is unclear how RA should be managed in 'today's world of multiple comorbidities'. Evidence that treatment of RA improves comorbidities is currently lacking, although some promising indirect observations are available. On the other hand, there is limited evidence that medication regularly prescribed for comorbidities, such as statins, might improve RA disease activity. Both ageing and comorbidity have an independent effect on commonly used outcome measures in the RA field, such as the Health Assessment Questionnaire (HAQ) and the clinical disease activity index (CDAI). Prospective studies, that also account for the presence of comorbidity in (elderly) RA patients are therefore urgently needed. To address gaps in knowledge, future research should focus on the complex interdependencies between RA, ageing and comorbidity. In addition, these findings should be integrated into daily clinical practice by developing and testing integrated and coordinated health care services. Adaptation of management recommendations is likely required. The elderly RA patient who also deals with (emerging) comorbidities presents a unique challenge to treating clinicians. A paradigm shift from disease-centered to goal-oriented approach is needed to develop adequate health care services for these patients.


Amenorrhea associated with carotenemia.
Data are presented for ten women with anovulation, nine of them with amenorrhea, who have associated carotenemia. Classic explanations for carotenemia in amenorrheic patients have been weight loss or anorexia nervosa, yet carotenemia in our patients appeared to be diet induced. All patients consumed a pure or predominantly vegetarian diet; there was no intake of red meats. Clinical and laboratory data of the patients are presented. The amenorrhea of the patient is consistent with hypothalamic hypogonadotropic anovulation (HHA). It appeared that diet modification not only led to reduction in carotene levels, but also improved the menstrual status. The association of carotenemia and menstrual disorders is reviewed. The possibility that carotenemia is related to the development of HHA is discussed.


The role of insulin and glucagon in experimental obstructive jaundice.
The oxidative phosphorylation of liver mitochondria is regulated by the amount of portal insulin available to the hepatocytes. Thus, hepatic energy is mediated by the values of blood sugar and insulin. Insulin and glucagon are the main fuel homeostats in the liver. This study was performed to investigate the concept of energy mediated by glucose, during the process of obstructive jaundice and its recovery. Experimental Wistar rats were studied, with bile duct tied for 4, 7 and 14 days respectively. The serum concentration and relative tissue concentration of insulin and glucagon were measured. And the common bile duct was tied for 4, 7 and 14 days, then relieved by time sequences for 4, 7 and 14 days. Serum concentration and relative tissue concentration of insulin and glucagon were also measured. When the common bile duct was tied for 4, 7, and 14 days respectively, the serum concentration and relative tissue concentration of insulin declined (p < 0.05) and glucagon concentration was elevated (p < 0.05). When the common bile duct was tied for 4, 7 and 14 days, then relieved by time sequences for 4, 7 and 14 days, the concentrations of insulin in both groups appeared to decline at first (p < 0.05) and then progressively increase (p < 0.05). The concentrations of glucagon exhibit the reverse behavior. Both serum and tissue concentration are elevated at first (p < 0.05), then progressively decline (p < 0.05). These studies indicated that, during obstructive jaundice, more fuel is demanded to make up for the energy deficiency. In spite of surgical or non-surgical relief of obstructive jaundice, the energy reserve is still not sufficiently recovered. The recovery of the hepatic energy reserve takes longer than we expected.


Serotonin antagonists in the five-choice serial reaction time task and their interactions with nicotine.
Much research has implicated the serotonin (5-HT) system in cognitive functioning and psychomotor stimulant abuse, but its role depends on the subtypes of 5-HT receptors involved and the nature of the behavioural task. Here we aimed to extend previous studies by examining the role of 5-HT1A and 5-HT2C receptors in attentional performance. The effects of the selective 5-HT antagonists WAY-100635 and SB-242084 were assessed alone and for interactions with nicotine in the five-choice serial reaction time task in rats. The effects of several doses of WAY-100635 were tested in combination with a fixed dose of nicotine, and then various doses of nicotine were tested in combination with SB-242084. Systemic administration of WAY-100635 and SB-242084 induced opposing effects on speed-related measures in the five-choice serial reaction time task, with antagonism at 5-HT1A receptors increasing omission errors and response latency, and antagonism at 5-HT2C receptors reducing both omissions and latency, and also increasing anticipatory responses; neither drug affected accuracy. Nicotine itself improved all main indices of attention, and there was preliminary evidence that the detrimental effects of WAY-100635 on response latency were weakened by nicotine. Conversely, treatment with SB-242084 enhanced all speed-related indices of performance to above the levels seen under the influence of nicotine alone, thus suggesting that 5-HT2C antagonists might be useful to decrease reaction times if used as an add-on therapy to treat attentional decline.


Distribution of Phenolic Compounds and Antioxidant Activity in Plant Parts and Populations of Seven Underutilized Wild Achillea Species.
Evaluation of phytochemical composition of underutilized Achillea species provides the primary selection of germplasms with the desired quality of raw material for their further applications. The aim of the study was to evaluate the comprehensive distribution patterns of phenolic compounds in seven wild Achillea spp. and their plant parts, and to assess their antioxidant activity. Plant material was collected from different sites in Turkey. A complex of hydroxycinnamic acids, flavonols and flavones was identified and quantified in methanolic extracts using HPLC-PDA method. Antioxidant activity was assessed by radical scavenging assay. The results showed that qualitative and qualitative profiles of caffeoylquinic acids and flavonoids were species-specific, explaining the characteristic patterns of their variation in the corresponding species and plant parts. The highest total amount of caffeoylquinic acids was detected in A. setacea. A. arabica exposed the highest accumulation of mono-caffeoylquinic acids and flavonoids with the greatest levels of quercetin and luteolin derivatives and the flavonol santin. Santin was detected in all plant parts of A. cappadocica, A. setacea, A. santolinoides subsp. wilhelmsii, and A. arabica. A notable antiradical capacity was confirmed in A. arabica, A. setacea and A. cappadocica plant extracts. The leaves of all studied species were found to have priority over inflorescences and stems in terms of radical scavenging activity. The new data complemented the information that may be relevant for the continuation of chemophenetic studies in the heterogeneous genus Achillea.


Surgical intervention for esophageal atresia in patients with trisomy 18.
Trisomy 18 is a common chromosomal aberration syndrome involving growth impairment, various malformations, poor prognosis, and severe developmental delay in survivors. Although esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a potentially fatal complication that can only be rescued through surgical correction, no reports have addressed the efficacy of surgical intervention for EA in patients with trisomy 18. We reviewed detailed clinical information of 24 patients with trisomy 18 and EA who were admitted to two neonatal intensive care units in Japan and underwent intensive treatment including surgical interventions from 1982 to 2009. Nine patients underwent only palliative surgery, including six who underwent only gastrostomy or both gastrostomy and jejunostomy (Group 1) and three who underwent gastrostomy and TEF division (Group 2). The other 15 patients underwent radical surgery, including 10 who underwent single-stage esophago-esophagostomy with TEF division (Group 3) and five who underwent two-stage operation (gastrostomy followed by esophago-esophagostomy with TEF division) (Group 4). No intraoperative death or anesthetic complications were noted. Enteral feeding was accomplished in 17 patients, three of whom were fed orally. Three patients could be discharged home. The 1-year survival rate was 17%: 27% in those receiving radical surgery (Groups 3 and 4); 0% in those receiving palliative surgery (Groups 1 and 2). Most causes of death were related to cardiac complications. EA is not an absolute poor prognostic factor in patients with trisomy 18 undergoing radical surgery for EA and intensive cardiac management.


A direct projection from superior colliculus to substantia nigra for detecting salient visual events.
Midbrain dopaminergic neurons respond to unexpected and biologically salient events, but little is known about the sensory systems underlying this response. Here we describe, in the rat, a direct projection from a primary visual structure, the midbrain superior colliculus (SC), to the substantia nigra pars compacta (SNc) where direct synaptic contacts are made with both dopaminergic and non-dopaminergic neurons. Complementary electrophysiological data reveal that short-latency visual responses in the SNc are abolished by ipsilateral lesions of the SC and increased by local collicular stimulation. These results show that the tectonigral projection is ideally located to relay short-latency visual information to dopamine-containing regions of the ventral midbrain. We conclude that it is within this afferent sensory circuitry that the critical perceptual discriminations that identify stimuli as both unpredicted and biologically salient are made.


Molecular map of the murine S region.
Eighteen overlapping cosmid clones spanning 240 kilobases and encoding the gene for factor B and two genes related to the fourth component of complement (C4) were isolated from a murine H-2d genomic library. Cosmid clones were identified by hybridization to human cDNA probes for factor B and C4 and were linked by chromosomal walking procedures. The cluster of clones contains two regions with sequences homologous to the C4 cDNA probe, both in the same orientation, representing a direct duplication of at least 55 kilobases of chromosomal DNA, separated by a shorter (less than 25 kilobases) segment of nonduplicated DNA. Restriction fragment-length polymorphism seen by using C4 probes maps these sequences to the S region of the major histocompatibility complex. 5' to the two C4-like sequences is an approximately equal to 40-kilobase-long region of chromosomal DNA remarkable for its lack of restriction fragment-length polymorphism, containing sequences homologous to the human factor B cDNA probe. These experiments demonstrate that the structural gene for factor B is located in the S region of the murine major histocompatibility complex and that this region contains an extensive direct duplication that contains the structural gene for mouse C4 and, we presume, for the sex-limited protein variant, Slp. RNA transfer blot analysis of total liver RNA from high C4- and low C4-producing strains showed that steady-state levels of C4-hybridizing RNA were much greater in high C4-producing strains. Regulation of circulating C4 levels in high C4 and low C4 strains is at least partly at the level of mRNA transcription, processing, or degradation.


Tritrichomonas foetus extracellular cysteine proteinase cleavage of bovine IgG2 allotypes.
Bovine trichomoniasis is a sexually transmitted disease associated with reproductive failure. Systemic immunization results in protective IgG antibodies in uterine and vaginal secretions. Because bovine IgG2 is a better opsonin than IgG1, it is potentially important in defense. Yet, Tritrichomonas foetus extracellular cysteine proteinase (TFECP) cleaves bovine IgG2, evading protective IgG2 responses. Variations in resistance of the 2 IgG2 allotypes to digestion may explain inherited differences in protection. To address this hypothesis, TFECP was incubated with both IgG2 allotypes at different concentrations and times. The digestion products were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, stained, and quantitated by image analysis. IgG2a was digested faster by TFECP than IgG2b. Differences in the sizes and numbers of digestion products were observed, but the presence of bands the size of Fc and Fd fragments indicated that both allotypes were cleaved at the hinge. Cysteine in the digestion mixture reduced the antibody molecules and increased the rate of digestion, but IgG2a was still more susceptible to cleavage than IgG2b in the absence of cysteine. Thus, not only reduced H chains can be cleaved by cysteine proteinase secreted by T. foetus but also intact functional antibody molecules. Because parasites may evade protective antibody responses by cleaving IgG2, animals with the more resistant IgG2b allotype may be better protected by immunization than animals with the more readily digested IgG2a allotype.


Job Satisfaction Among Methadone Maintenance Treatment Clinic Service Providers in Jiangsu, China: A Cross-sectional Survey.
Service providers' job satisfaction is critical to the stability of the work force and thereby the effectiveness of methadone maintenance treatment (MMT) programs. This study aimed to explore MMT clinic service providers' job satisfaction and associated factors in Jiangsu, China. This secondary study used baseline data of a randomized interventional trial implemented in Jiangsu, China. A survey was conducted among 76 MMT service providers using the computer-assisted self-interview (CASI) method. Job satisfaction responses were assessed via a 30-item scale, with a higher score indicating a higher level of job satisfaction. Perceived institutional support and perceived stigma due to working with drug users were measured using a 9-item scale. Correlation and multiple linear regression analyses were performed to identify factors associated with job satisfaction. Correlation analyses found a significant association between job satisfaction and having professional experience in the prevention and control of HIV, other sexually transmitted infections, or other infectious diseases (P = 0.046). Multiple regression analyses revealed that working at MMT clinics affiliated with Center for Disease Control and Prevention sites was associated with a lower level of job satisfaction (P = 0.014), and perception of greater institutional support (P = 0.001) was associated with a higher level of job satisfaction. Job satisfaction among MMT clinic service providers was moderate in our study. Our findings suggest that institutional support for providers should be improved, and that acquisition of additional expertise should be encouraged.


Mitochondrial targeting sequences may form amphiphilic helices.
Twenty three mitochondrial targeting sequences have been analysed with regard to their potential for forming amphiphilic helices. It is shown that most if not all of these sequences can be expected to form helices with high hydrophobic moments in a suitable environment. In the few cases studied so far, the segments of maximal hydrophobic moment coincide closely with 'critical' regions defined by deletions and point mutations.


[Effects of pulmonary rehabilitation on vital capacity in patients with chronic pulmonary emphysema].
To evaluate the effects of pulmonary rehabilitation on pulmonary function, 15 patients with chronic pulmonary emphysema underwent pulmonary rehabilitation for six weeks as inpatients. Pulmonary rehabilitation consisted of relaxation techniques, breathing retraining, thoracic massage, physical exercise, and walking. In 8 of the 15 patients vital capacity increased by more than 200 ml (over 10%), and in 7 of the 15 patients the load of maximal exercise increased by more than 5 watts (over 10%). Increases in vital capacity were not associated with increases in maximal exercise load. The percent change in vital capacity associated with pulmonary rehabilitation correlated significantly with the percent change in tidal volume and the percent change in expiratory minute ventilation at the maximal load. The percent change in tidal volume at the maximal load correlated significantly with the percent change in maximum oxygen uptake. We attribute the increase in vital capacity to an improvement in thoracic cage movement. These findings suggest that pulmonary rehabilitation can increase vital capacity in some patients with chronic pulmonary emphysema, and that such an increase is not directly connected to increases in exercise capacity.


Does the coordination between posture and movement during human whole-body reaching ensure center of mass stabilization?
The whole-body center of mass (CoM) has been classically regarded as the stabilized reference value for human voluntary movements executed upon a fixed base of support. Axial synergies (opposing displacements of head and trunk with hip segments) are believed to minimize antero-posterior (A/P) CoM displacements during forward trunk movements. It is also widely accepted that anticipatory postural adjustments (APAs) create forces of inertia that counteract disturbances arising from the moving segment(s). In the present study, we investigated CoM stabilization by axial synergies and APAs during a whole-body reaching task. Subjects reached towards an object placed on the ground in front of them in their sagittal plane using a strategy of coordinated trunk, knee, and hip flexion. The reaching task imposed constraints on arm-trajectory formation and equilibrium maintenance. To manipulate equilibrium constraints, differing conditions of distance and speed were imposed. The comparison of distance conditions suggested that axial synergies were not entirely devoted to CoM stabilization: backward A/P hip displacements reduced as head and trunk forward A/P displacements increased. Analysis of upper- and lower-body centers of mass in relation to the CoM also showed no strict minimization of A/P CoM displacements. Mechanical analysis of the effects of APAs revealed that, rather than acting to stabilize the CoM, APAs created necessary conditions for forward CoM displacement within the base of support in each condition. The results have implications for the CoM as the primary stabilized reference for posture and movement coordination during whole-body reaching and for the central control of posture and voluntary movement.


Assessing the Efficacy of Broad-Spectrum Antibiotics in Controlling Bacterial Contamination in the In Vitro Micropropagation of Ginger (Zingiber officinale Rosc).
Ginger (Zingiber officinale Rosc) (Zingiberaceae) is a livelihood and commercial crop in Ethiopia. But, the availability of clean and healthy planting materials has become a problem due to wilt disease, caused by Ralstonia solanacearum Biovar 3 Race 4. This problem obliged growers to seek for tens of millions of vigorous and disease-free planting materials very quickly via in vitro micropropagation of shoot tip explants. For this purpose, protocols of sterilizing shoot tip explants and controlling bacterial contamination of one Ethiopian ginger cultivar called Deribo were tested. Hence, this article reports the finding of a study that aimed at testing the (a) effectiveness of three sterilization agents, namely, 0.25% w/v RBK (composed of ridomile, bayleton, and kocide at 1 : 1 : 1 ratio), 0.50% v/v NaOCl, and 70% v/v ethanol at three different treatment times in combination with 0.25% HgCl2; (b) efficacy of four broad-spectrum antibiotics and their combinations in controlling bacterial contaminants of ginger shoot tip explants and in vitro micropropagation media; and (c) effects of the antibiotics on the shooting performances of the explants of the cultivar. A 0.50% v/v NaOCl at exposure time of 20 min followed by 0.25% HgCl2 has resulted in 80% contamination-free and 70% live explants after three weeks of incubation. Likewise, cefotaxime at 50, 100, and 200 mg/L and cefotaxime plus streptomycin at 25, 50, and 100 mg/L yielded 87 to 93% contamination-free microshoots after three weeks of culturing. The number of explants killed by the antibiotics increased with increasing the concentration of the antibiotics. Cefotaxime at 50 mg/L and cefotaxime plus streptomycin at 25 mg/L yielded significantly highest mean microshoots per explant (7.10 ± 0.36 and 7.51 ± 0.27, respectively) and mean shoot length (4.2 ± 0.26 and 3.56 ± 0.17 cm, respectively). Some of the microshoots showed some yellowing. But, they turned green and grew normal after subcultured into fresh, antibiotics-free culture media. These findings are important foundations towards developing more optimized protocols of sterilizing explants and controlling bacterial contaminants for large-scale in vitro micropropagation of the Deribo ginger cultivar.


Psychological Predictors of Precautionary Behaviors in Response to COVID-19: A Structural Model.
The first lines of defense during an epidemic are behavioral interventions, including stay-at-home measures or precautionary health training, aimed at reducing contact and disease transmission. Examining the psychosocial variables that may lead to greater adoption of such precautionary behaviors is critical. The present study examines predictors of precautionary practices against coronavirus disease 2019 (COVID-19) in 709 Mexican participants from 24 states. The study was conducted via online questionnaire between the end of March and the beginning of April 2020, when the pandemic response was in its initial stages in Mexico. The instrument included demographic items, as well as scales assessing COVID-19-resembling symptoms, empathy, impulsivity, anhedonic depression, general health practices, alcohol consumption, and COVID-19-associated precautionary behaviors. Most participants reported adopting limited social distancing or other precautionary behaviors against COVID-19. The results of a structural equation model demonstrated that the presence of COVID-19 symptoms was related to impulsivity and general health behaviors. However, no direct association between precautionary behaviors and the presence of COVID-19 symptoms was found. In turn, precautionary behaviors were more prevalent among participants who reported higher empathy and general health behaviors and were inhibited indirectly by impulsivity via alcohol consumption. Furthermore, the model suggests that anhedonic depression symptoms have a negative indirect effect on precautionary behaviors via general health behaviors. Finally, impulsivity showed a negative direct effect on general health behavior. These results highlight the role that general physical health and mental health play on precautionary behavior and the critical importance of addressing issues such as depression, general health behaviors, and impulsivity in promoting safe actions and the protection of self and others.


Intereye Symmetry of 24-Hour Intraocular Pressure-related Patterns in Untreated Glaucoma Patients Using a Contact Lens Sensor.
Scarce data are available on the symmetry of 24-hour intraocular pressure (IOP) variations between fellow eyes of glaucoma patients, and such evidence could have profound consequences on the interpretation of monocular therapeutic trials. The objective is to evaluate the intereye correlation of continuously measured circadian IOP-related patterns in untreated glaucoma patients. In this single-center prospective study, a total of 29 untreated patients with open-angle glaucoma underwent bilateral ambulatory 24-hour monitoring of IOP-related patterns using a contact lens sensor (CLS; SENSIMED Triggerfish). IOP was measured before and after CLS monitoring using Goldmann applanation tonometry. Intereye agreement of 24-hour patterns was calculated using Spearman correlation (r) of raw data and after cosinor rhythmometry modeling. Complete bilateral CLS data could be obtained in 20 patients (mean age: 55.5±15.7 y; 51.7% women). On average, intereye correlation was r=0.76±0.19 (range: 0.16 to 0.95) and r=0.77±0.15 (range: 0.49 to 0.91), after excluding 8 patients with lower quality recordings. Cosine rhythmometry modeling showed mean acrophases occurring at 4:21±2:20 AM in left eyes and 3:39±1:50 AM in right eyes (r=0.48; P=0.034). Mean acrophase amplitude was 110.9±51.9 for left eyes and 107.8±46.2 for right eyes (r=0.79; P<0.001). No serious adverse events related to CLS monitoring were recorded. Transient conjunctival hyperemia (13 patients) and blurred vision (11 patients) were the most frequent adverse events. In this group of untreated glaucoma patients, there was good intereye agreement for circadian IOP-related patterns using the CLS. These results show a higher degree of intereye symmetry, in terms of IOP peak timings and amplitudes, than previously reported with standard tonometry.


Are Motor Control and Regulation Problems Part of the ASD Motor Profile? A Handwriting Study.
The primary aim of this study was to kinematically assess how children with autism spectrum disorder (ASD) plan and control their handwriting actions. Forty-three boys aged between 8 to 12 years were included in the present analysis; 23 with ASD and 20 typically developing (TD) controls. Sophisticated objective and quantifiable assessment of movement metrics and dynamics was applied across a series of basic cursive handwriting sequences. Children with ASD demonstrated atypical control of handwriting metrics and dynamics, as well as significantly greater neuromotor noise relative to age-matched peers. They also engaged in less regular monitoring and regulation of their movement during the handwriting task. This study provides new insights into the way children with ASD plan and sequence their handwriting movements. Overall, results revealed that even at a basic level, children with ASD appear to have a breakdown in their ability to control and regulate their handwriting movements. This has important implications for the school-aged child who constantly engages in handwriting tasks within the classroom environment and provides insight into possible directions for future intervention.


How can female germline stem cells contribute to the physiological neo-oogenesis in mammals and why menopause occurs?
At the beginning of the last century, reproductive biologists have discussed whether in mammalian species the fetal oocytes persist or are replaced by neo-oogenesis during adulthood. Currently the prevailing view is that neo-oogenesis is functional in lower vertebrates but not in mammalian species. However, contrary to the evolutionary rules, this suggests that females of lower vertebrates have a better opportunity to provide healthy offspring compared to mammals with oocytes subjected to environmental threats for up to several decades. During the last 15 years, a new effort has been made to determine whether the oocyte pool in adult mammals is renewed as well. Most recently, Ji Wu and colleagues reported a production of offspring from female germline stem cells derived from neonatal and adult mouse ovaries. This indicates that both neonatal and adult mouse ovaries carry stem cells capable of producing functional oocytes. However, it is unclear whether neo-oogenesis from ovarian somatic stem cells is physiologically involved in follicular renewal and why menopause occurs. Here we review observations that indicate an involvement of immunoregulation in physiological neo-oogenesis and follicular renewal from ovarian stem cells during the prime reproductive period and propose why menopause occurs in spite of persisting ovarian stem cells.


[Chemical constituents of Dolomiaea souliei].
To study the chemical constituents of Dolomiaea souliei. Various chromatographic techniques were adopted to separate the constituents, and the spectrum analysis was made to identify their structures. Seventeen compounds were isolated and identified as: dehydrocostus lactone (1), costunolide (2), mokko lactone (3), santamarine(4), reynosin (5), 4alpha-hydroxy-4beta-methyldihydrocostol (6), sulfocostunolide A (7), beta-costic acid (8), beta-cyclocostunolide (9), vladinol A (10), ursolic acid (11), betulinic acid (12), betulin (13), dibutyl terephthalate (14), dibutyl phthalate (15), uridine (16), and emodin (17). Compounds 6-9 and 12-17 were obtained from this genus for the first time, and compound 11 was obtained from this plant for the first time.


Topical Silymarin Cream as a Novel Therapy Versus Salicylic Acid Peels in Acne Vulgaris: A Split-Face Clinical Trial.
Acne vulgaris is a common dermatological condition that greatly impacts patients' self-confidence. Ongoing research is conducted to explore new treatment modalities. Silymarin owns special characteristics that qualify it as a possible treatment for acne vulgaris. We evaluated the efficacy and safety of silymarin cream as a new therapeutic option against salicylic acid peels in the treatment of mild to moderate acne vulgaris. A split-face, comparative, Quasi-experimental clinical trial included 30 patients with acne vulgaris. Salicylic acid 30% peels were applied as an office procedure to one half of the face every 2 weeks for 3 months. Topical silymarin 1.4% cream was prescribed as a home treatment, twice daily, to the other half of the face for 3 months. The results were evaluated using the Global Acne Grading System (GAGS), photographic evaluation, and patient self-assessment scale. The adverse effects during treatment were recorded. The sample size was calculated by Stata/IC 16.1. After treatment, a significant reduction of GAGS was noted on both sides of the face, with an insignificant difference between both treatments. The comparative photographic evaluation and patient self-assessment scale were also insignificant. Hyperpigmentation was recorded in 2 cases on the salicylic acid-treated side. No side effects for silymarin cream were observed. Topical silymarin cream 1.4% showed comparable results to Salicylic acid 30% peels. It can be considered a promising safe treatment modality for mild to moderate acne vulgaris.


[Acoustic follow-up of nocturnal bronchial obstruction therapy].
Long acting beta 2-agonists belong to the basic therapy of COPD. Especially patients with nocturnal respiratory problems may benefit from this therapy. Long term recording of lung sounds is a new method for quantitative measurements of bronchial obstructions. In combination with polysomnography an evaluation of cardiorespiratory parameters and sleep structure is possible. A total of 10 patients (8 male and 2 female) with moderate COPD (FEV1 58 +/- 11 %) and signs of bronchial obstruction were investigated. The combination of acoustic long term recording and polysomnography was done for 2 or 3 nights without and under therapy (long acting beta 2-agonist, 50 microg Salmeterol). In all patients we could find nocturnal bronchial obstruction events. Nocturnal wheezing time was reduced during therapy to 33 +/- 17 % (1. therapy night, n. s.) compared to 49 +/- 30 % without therapy (control night) and to 17 +/- 17 % (2. therapy night, n = 6, p < 0.05) vs. 51 +/- 30 % (control night, n = 6). Sleep efficiency and REM sleep increased (n. s.) under therapy, deep sleep stages NREM III/IV were nearly the same. Acoustic long term monitoring confirms the reduction of nocturnal bronchial obstructions under therapy with beta 2-agonists. A better sleep quality may be expected from the improvement of the respiratory situation during sleep.


Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice.
Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers. Here, we show that CTLA4-Ig is additionally able to inhibit established T cell responses independently of B cells. CTLA4-Ig inhibited the in vivo cytolytic activity of donor-specific CD8+ T cells, and the production of IFNγ by graft-infiltrating T cells. Delayed CTLA4-Ig treatment did not reduce the numbers of graft-infiltrating T cells nor prevented the accumulation of antigen-experienced donor-specific memory T cells in the spleen. Nevertheless, delayed CTLA4-Ig treatment successfully maintained long-term graft acceptance in the majority of recipients that had experienced a rejection crisis, and enabled the acceptance of secondary BALB/c heart grafts transplanted 30 days after the first transplantation. In summary, we conclude that delayed CTLA4-Ig treatment is able to partially halt ongoing T cell-mediated acute rejection. These findings extend the functional efficacy of CTLA4-Ig therapy to effector T cells and provide an explanation for why CTLA4-Ig-based immunosuppression in the clinic successfully maintains long-term graft survival after T cell-mediated rejection.


Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition.
We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.


Pharmacological aspects of mianserin.
S(+)-mianserin is the more potent enantiomer of mianserin in pharmacological tests indicative for antidepressant activity. Pharmacological tests indicative for sedation suggest that sedative effects are similar for mianserin and its enantiomers. Racemic mianserin had the optimal therapeutic ratio of antidepressant-like activity versus sedative properties when assessed by computerised EEG in healthy volunteers participating in a double-blind placebo-controlled single dose trial. Of the known metabolites, desmethylmianserin and 8-hydroxymianserin substantially retain pharmacological properties indicative for antidepressant activity but are less active than mianserin in tests indicative for sedation. Mianserin-N-oxide is inactive or only weakly active in most pharmacological tests. Desmethylmianserin occurs in human plasma after both single and multiple dosage to an extent of about one-third that of mianserin. Mianserin has optimal clinical efficacy as the racemate. Desmethyl-mianserin and 8-hydroxymianserin are pharmacologically active metabolites and may contribute to the overall antidepressant effects of mianserin.


[Intercultural health: elements to the construction of its conceptual bases].
Over the past few years, intercultural health has become an emerging issue in health policy. Intercultural health is an approach to create a better communication between patients and providers. In the short term, this approach incorporates patient's culture background in health care, improving intercultural communication strategies to generate, in the long term, a health system adapted to the medical culture of patients. This article explores the underlying concepts in the intercultural health approach, such as cultural diversity and medical systems as complex models of thoughts and behaviors.


The effect of antioxidants on ozone-induced airway hyperresponsiveness in dogs.
The role of oxygen radicals in causing ozone-induced airway hyperresponsiveness in dogs was examined by pretreating dogs with allopurinol and/or deferoxamine mesylate (desferal), which are inhibitors of oxygen radical generation, before ozone inhalation. Acetylcholine airway responsiveness was measured before and after either air or ozone inhalation (3 ppm for 20 min) on 5 experimental days separated by at least 2 wk. On each day, the dogs were pretreated intravenously with allopurinol (50 mg/kg) followed by inhaled desferal (1,000 mg inhalation) or with allopurinol followed by the diluent for desferal or with the diluent for allopurinol and desferal or with both diluents. The effect of ozone on acetylcholine airway responsiveness was expressed as the differences in the log-transformed preozone-postozone acetylcholine provocative concentrations. When dogs received both diluents or either treatment alone, ozone inhalation caused airway hyperresponsiveness. The mean log differences for the preozone-postozone acetylcholine provocative concentration were 0.804 (SEM, 0.17) for both diluents, 0.524 (SEM, 0.16) for allopurinol alone, and 0.407 (SEM, 0.22) for desferal alone. However, the combination of allopurinol and desferal significantly inhibited the development of ozone-induced airway hyperresponsiveness, the log difference being 0.195 (SEM, 0.11) (p less than 0.05), without inhibiting ozone-induced neutrophil influx into the airways. The results suggest that the production of oxygen radicals is important in the pathogenesis of ozone-induced airway hyperresponsiveness.


[Use of tianeptine (coaxil) in the treatment of late-life depression].
Efficacy and safety of tianeptine (coaxil) for treatment of depressions in old age were studied in 15 depressed patients at the age of 54-78 years meeting ICD-10 criteria for depressive episode. Open method with a set of rating scales was employed. After the 28-day treatment relief of depressive symptoms was registered by all the scales since the therapy day 7. The degree of improvement on HAMD-scale was 50%, amount of responders--60%. The improvement of cognitive functions by the end of therapy was noted. Clinical predictors of Coaxil efficacy were determined by means of correlation and factor analyses. Relationship between the therapy efficacy and severity of some symptoms in the structure of depression were analyzed. The greatest efficacy of Coaxil was found in depression with prevalence of asthenic and somatovegetative symptoms, in patients with mild anxiety opposite the decrease of the effect in those with severe agitated depressions. The analysis of both frequency and severity of the side-effects has shown good tolerance to Coaxil. The adverse effects manifested with mild gastrointestinal disturbances and drowsiness during daytime.


Isolation and characterization of a novel fucoidan-degrading microorganism.
A bacterium utilizing fucoidan from the brown alga Cladosiphon okamuranus as sole carbon source was isolated and identified as Flavobacterium sp. F-31. The strain produced intracellular enzymes involved in fucoidan degradation and desulfation, but desulfation activity was not detected until the molecular weight of fucoidan fell to less than several tens of thousands due to enzymatic degradation. Only fucoidan proved to be an inducible substance for the production of the degrading enzymes.


Effects of UV-B radiation on leaf hair traits of invasive plants-Combining historical herbarium records with novel remote sensing data.
Ultraviolet-B (UV-B) radiation is a key but under-researched environmental factor that initiates diverse responses in plants, potentially affecting their distribution. To date, only a few macroecological studies have examined adaptations of plant species to different levels of UV-B. Here, we combined herbarium specimens of Hieracium pilosella L. and Echium vulgare L. with a novel UV-B dataset to examine differences in leaf hair traits between the plants' native and alien ranges. We analysed scans of 336 herbarium specimens using standardized measurements of leaf area, hair density (both species) and hair length (H. pilosella only). While accounting for other bioclimatic variables (i.e. temperature, precipitation) and effects of herbivory, we examined whether UV-B exposure explains the variability and geographical distribution of these traits in the native (Northern Hemisphere) vs. the alien (Southern Hemisphere) range. UV-B explained the largest proportion of the variability and geographical distribution of hair length in H. pilosella (relative influence 67.1%), and hair density in E. vulgare (66.2%). Corresponding with higher UV-B, foliar hairs were 25% longer for H. pilosella and 25% denser for E. vulgare in records from the Southern as compared to those from the Northern Hemisphere. However, focusing on each hemisphere separately or controlling for its effect in a regression analysis, we found no apparent influence of UV-B radiation on hair traits. Thus, our findings did not confirm previous experimental studies which suggested that foliar hairs may respond to higher UV-B intensities, presumably offering protection against detrimental levels of radiation. We cannot rule out UV-B radiation as a possible driver because UV-B radiation was the only considered variable that differed substantially between the hemispheres, while bioclimatic conditions (e.g. temperature, precipitation) and other considered variables (herbivory damage, collection date) were at similar levels. However, given that either non-significant or inconclusive relationships were detected within hemispheres, alternative explanations of the differences in foliar hairs are more likely, including the effects of environment, genotypes or herbivory.


Properties of herbage in relation to equine dysautonomia: biochemical composition and antioxidant and prooxidant actions.
To investigate the etiology of equine dysautonomia (ED), a degenerative polyneuropathy affecting grazing horses, the biochemical composition and antioxidant/prooxidant activities of aqueous extracts of plants collected from ED pastures were determined. Plants collected immediately after an outbreak of ED had reduced antioxidant and weak prooxidant activities when compared with control plants (plants collected from ED pastures out of ED season and control plants from ED pastures that were grown under favorable conditions). ED plants also had significantly increased concentrations of fructose and low molecular weight phenolic compounds, significantly more of one amino acid zone (probably valine), significantly less tartaric acid, and a nonsignificant decrease in ascorbic acid content when compared with control plants from ED pastures that were grown under favorable conditions. These findings suggest that ED plants may be under oxidative stress, possibly due to chilling, drought, or fungal colonization. However, experimental drought and chilling of plants did not reproduce the biochemical alterations identified in ED plants. It is possible that the altered biochemical content of ingested plants may contribute, directly or indirectly, to the development of ED in grazing horses.


Prevalence and associated factors of vitamin D deficiency after Roux-en-Y gastric bypass: A systematic review and meta-analysis.
To estimate the prevalence and associated factors of vitamin D deficiency (VDD) after Roux-en-Y gastric bypass (RYGB). PubMed, EMBASE, and CENTRAL were searched for relevant records from inception to March 17, 2023, using search terms: vitamin D, vitamin D3, vitamin D deficiency, hypovitaminosis D, gastric bypass, and RYGB. Studies were eligible for inclusion if they provided related data on VDD prevalence after RYGB. Of 1119 screened studies, 72 studies involving 7688 individuals were enrolled in the final analysis. The prevalence estimates of VDD after RYGB were 42%. Subgroup analyses suggested the pooled prevalence of postoperative VDD was 35% for follow-up duration ≤1 year, 43% for >1 and ≤5 years, and 54% for >5 years. Meta-regression showed that VDD prevalence was positively correlated with follow-up time. Also, the prevalence was higher in studies with inadequate vitamin D supplementation than in those with adequate supplementation and in Asia population than in those from South America, Europe, and North America. Other factors associated with high VDD prevalence after RYGB included high presurgical VDD prevalence, non-compliant patients, and black populations. No significant association existed between VDD and alimentary length. VDD presented a high prevalence in patients following RYGB. It occurred more frequently with longer postoperative follow-up time. Population-specific vitamin D supplementation measures, targeted treatment for presurgical VDD, improved patient compliance, and periodical follow-ups were necessary to reduce VDD and other adverse outcomes.


Implementation of psychological clinical trials in epilepsy: Review and guide.
The International League Against Epilepsy (ILAE) Neuropsychiatry commission and United States Institute of Medicine report both identified cognitive and psychological comorbidities as a significant issue for individuals with epilepsy, with rates as high as 60%. However, there is a paucity of evidence-based treatments for many psychological conditions (e.g., learning disorders, cognitive disorders, behavioral disorders). Because of inherent challenges in the implementation of psychological therapy trials and specific considerations for the population with epilepsy, the focus of the current review was to provide guidance and recommendations to conduct psychological trials for individuals with epilepsy. Several key areas will be discussed, including selection of patients, trial design, psychological intervention considerations, outcomes and evaluation of results, publication of trial results, and special issues related to pediatric clinical trials. Rigorously designed psychological therapy trials will set the stage for evidence-based practice in the care of individuals with epilepsy, with the goal of improving seizures, side effects, and HRQOL.


ISO 15189 Accreditation: Navigation Between Quality Management and Patient Safety.
Accreditation is a valuable resource for clinical laboratories and the development of an International Standard for their accreditation represented a milestone on the path towards improved quality and safety in laboratory medicine. The recent revision of the International Standard, ISO 15189, has further strengthened its value not only for improving the quality system of a clinical laboratory but also for better answering the request for competence, focus on customers' needs and ultimate value of laboratory services. Although in some countries more general standards such as ISO 9001 for quality systems or ISO 17025 for testing laboratories are still used, there is increasing recognition of the value of ISO 15189 as the most appropriate and useful standard for the accreditation of medical laboratories. In fact, only this International Standard recognizes the importance of all steps of the total testing process, namely extra-analytical phases, the need to focus on technical competence in addition to quality systems, and the focus on customers' needs. However, the number of accredited laboratories largely varies between European countries and also major differences affect the approaches to accreditation promoted by the national bodies. In particular, some national accreditation bodies perpetuate the use of fixed scopes, while the European co-operation for accreditation (EA) and the European Federation of Laboratory Medicine (EFLM) Working Group promote the use of flexible scopes. Major issues in clinical laboratory accreditation are the verification of examination procedures for imprecision, trueness and diagnostic accuracy and for estimating measurement uncertainty. In addition, quality indicators (QIs) are a fundamental requirement of the ISO 15189 International Standard.


Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging.
Malignant mesothelioma (MM) is a fatal malignancy with a rapidly increasing incidence in industrialized countries because of the widespread use of asbestos in the past centuries. Early diagnosis of MM is critical for a better prognosis, but this is often difficult because of the lack of disease-specific diagnostic imaging. Here, we report that manganese-enhanced magnetic resonance imaging (MEMRI) represents a promising approach for a more selective mesothelioma imaging by monitoring a high-level expression of manganese-superoxide dismutase (Mn-SOD), which is observed in many MM. We found that most human MM cells overexpressed Mn-SOD protein compared with human mesothelial cells and that NCI-H226 human MM cells highly expressed Mn-SOD and augmented Mn accumulation when loaded with manganese chloride (MnCl(2)). The cells showed marked T(1)-signal enhancement on in vitro MRI after incubation with MnCl(2) because of the T(1) shortening effect of Mn(2+). H226 subcutaneous tumor was preferentially enhanced compared with a lung adenocarcinoma cell tumor and another human MM cell tumor in MnCl(2)-enhanced T(1)-weighted MR image (T(1)WI), correlating with their respective Mn-SOD expression levels. Moreover, in a more clinically relevant setting, H226 xenografted pleural tumor was markedly enhanced and readily detected by MEMRI using manganese dipyridoxyl diphosphate (MnDPDP), a clinically used contrast agent, as well as MnCl(2). Therefore, we propose that MEMRI can be a potentially powerful method for noninvasive detection of MM, with high spatial resolution and marked signal enhancement, by targeting Mn-SOD.


Development of seaweed biomass as a biosorbent for metal ions .
Three seaweed species collected from Hong Kong waters were screened for their adsorption abilities for Cu2+, Ni2+ and Zn2+ and Ulva lactuca having the highest metal ion removal capacity (RC) was chosen for further study. Effects of algal biomass and medium pH on the metal ions RC of Ulva lactuca were determined and optimized. Under the optimal conditions of the corresponding metal ions, the algal Cu2+, Ni2+ and Zn2+ RCs were 65.54, 21.00 and 49.54 mg/g, respectively. The presence of other cations and anions affected the metal ions adsorption by the seaweed. The effect was dependent on the between the target metal ions and other cations/anions. The kinetic study revealed that the adsorption of Cu2+, Ni2+ and Zn2+ by Ulva lactuca fitted the Langmuir isotherm. Comparing with 0.1 M HCl, citric acid, thiourea, EDTA and HNO3, 0.1 M H2SO4 efficiently recovered close to 100% adsorbed metal ions from Ulva lactuca. In three successive adsorption-desorption cycles, reduction in metal ion RCs was found in the second and third cycles, but almost all adsorbed metal ion could be recovered.


Long-term wear effects on nanosilver release from commercially available food contact materials.
Potential consumer exposure to nanoparticles (NPs) from nanoenabled food contact materials (FCMs) has been a driving force for migration studies of NPs from FCMs. Although NP migration from fresh, unused FCMs was not previously observed, conditions that result in significant changes to the surface of FCMs have not been investigated for NP migration into food. Therefore, a quantitative assessment of nanoparticle release from commercially available nanosilver-enabled FCMs was performed using an abrasion protocol to simulate cleaning, cutting, scraping and other stressful use conditions. Laser scanning confocal microscopy (LSCM) analysis showed a general increase in root mean square (RMS) roughness after FCM abrasion, and particle count (for particle sizes from 80 nm to 960 nm) at the surface was 4 orders of magnitude higher for the abraded FCMs. Migration was evaluated using both water and 3% (v/v, volume fraction) acetic acid as food simulants. Low concentrations of total Ag were detected in water simulants with a small portion (<10 ng dm-2) in the form of silver nanoparticles (AgNPs). Median particle diameter ranged from 39 nm to 50 nm with particle number concentrations on the order of 106 particles dm- 2. Total Ag migration into 3% (v/v) acetic acid was significantly higher than in water; however, 3% (v/v) acetic acid was not suitable for evaluation of NP release due to dissolution of AgNPs to Ag+ under acidic solution chemistries.


Factors Influencing Self-confidence in the Maternal Role among Early Postpartum Mothers.
The purpose of this study was to identify the influencing factors of mothers' confidence in their maternal role during the early postpartum period. Participants were 178 postpartum women who delivered at three specialized obstetrics and gynecology facilities and used the postpartum care facility in city B. Data were collected from February to April, 2012 using the scales of measurements of self-confidence in maternal role performance, maternal self-esteem, mother-to-infant attachment, social support, and childcare stress. Descriptive statistics, Pearson correlation coefficients, and stepwise multiple regression were used with the SPSS/WIN 18.0 program to analyze the data. The scores for self-confidence in the maternal role showed significant negative correlations with the scores of childcare stress (r=-.40, p<.001). Parity and maternal attachment were significant predictors and accounted for 97.4% of the variance in self-confidence in the maternal role. To strengthen self-confidence in the maternal role of early postpartum mothers, prenatal class programs need to be complemented in order to reduce childcare stress and promote mother-to-infant attachment.


T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis.
Clinical and histologic similarities between various eczematous disorders point to a common efferent pathway. We demonstrate here that activated T cells infiltrating the skin in atopic dermatitis (AD) and allergic contact dermatitis (ACD) induce keratinocyte (KC) apoptosis. KCs normally express low levels of Fas receptor (FasR) that can be substantially enhanced by the presence of IFN-gamma. KCs are rendered susceptible to apoptosis by IFN-gamma when FasR numbers reach a threshold of approximately 40,000 per KC. Subsequently, KCs undergo apoptosis induced by anti-FasR mAb's, soluble Fas ligand, supernatants from activated T cells, or direct contact between T cells and KCs. Apoptotic KCs show typical DNA fragmentation and membrane phosphatidylserine expression. KC apoptosis was demonstrated in situ in lesional skin affected by AD, ACD, and patch tests. Using numerous cytokines and anti-cytokine neutralizing mAb's, we found no evidence that cytokines other than IFN-gamma participate in this process. In addition, apoptosis-inducing pathways other than FasR triggering were ruled out by blocking T cell-induced KC apoptosis by caspase inhibitors and soluble Fas-Fc protein. Responses of normal human skin and cultured skin equivalents to activated T cells demonstrated that KC apoptosis caused by skin-infiltrating T cells is a key event in the pathogenesis of eczematous dermatitis.


Towards a naturalistic brain-machine interface: hybrid torque and position control allows generalization to novel dynamics.
Realization of reaching and grasping movements by a paralytic person or an amputee would greatly facilitate her/his activities of daily living. Towards this goal, control of a computer cursor or robotic arm using neural signals has been demonstrated in rodents, non-human primates and humans. This technology is commonly referred to as a Brain-Machine Interface (BMI) and is achieved by predictions of kinematic parameters, e.g. position or velocity. However, execution of natural movements, such as swinging baseball bats of different weights at the same speed, requires advanced planning for necessary context-specific forces in addition to kinematic control. Here we show, for the first time, the control of a virtual arm with representative inertial parameters using real-time neural control of torques in non-human primates (M. radiata). We found that neural control of torques leads to ballistic, possibly more naturalistic movements than position control alone, and that adding the influence of position in a hybrid torque-position control changes the feedforward behavior of these BMI movements. In addition, this level of control was achievable utilizing the neural recordings from either contralateral or ipsilateral M1. We also observed changed behavior of hybrid torque-position control under novel external dynamic environments that was comparable to natural movements. Our results demonstrate that inclusion of torque control to drive a neuroprosthetic device gives the user a more direct handle on the movement execution, especially when dealing with novel or changing dynamic environments. We anticipate our results to be a starting point of more sophisticated algorithms for sensorimotor neuroprostheses, eliminating the need of fully automatic kinematic-to-dynamic transformations as currently used by traditional kinematic-based decoders. Thus, we propose that direct control of torques, or other force related variables, should allow for more natural neuroprosthetic movements by the user.


Mother-to-child HIV-2 transmission: comparison with HIV-1 and evaluation of factors influencing the rate of transmission. A systematic review.
A review and collection of data on HIV-2 mother-to-child transmission (MTCT) is absent in the literature. This systematic review and meta-analysis aims to provide a pooled estimate of the rate of HIV-2 MTCT and to identify factors influencing the rate of transmission. PubMed and EMBASE were used to identify eligible publications using a sensitive search strategy. All publications until February 2021 were considered; 146 full-text articles were assessed. Observational studies describing the rate of HIV-2 MTCT in a defined HIV-2 infected study population were included. Other publication types and studies describing HIV-1 or dually infected populations were excluded. Nine studies consisting of 901 mother-child pairs in West Africa, France and Portugal were included in the meta-analysis. The pooled rate estimate of HIV-2 MTCT for antiretroviral therapy-naïve women was 0.2% (95% CI 0.03 to 1.47%), considerably lower than that for HIV-1. The levels of maternal HIV RNA and CD4 cell count were positively related to the vertical transmission rate. Maternal HIV-2 infection did not significantly affect perinatal mortality. It was concluded that the vertical transmission of HIV-2 is lower than that of HIV-1. Maternal viral load and CD4 cell count appear to influence the rate of HIV-2 MTCT.


Outcomes of open surgical repair for chronic type B aortic dissections.
Open surgical repair (OSR) for chronic type B aortic dissection (CTBAD) has an associated morbidity and mortality. The role of thoracic endovascular aortic repair (TEVAR) in CTBAD has not been determined. We analyzed our contemporary experience of CTBAD undergoing OSR to identify high-risk patients who may be considered for TEVAR. From 1999 to 2010, 221 patients had repair of descending thoracic and thoracoabdominal aortic aneurysms, including 86 patients with CTBADs. We analyzed this cohort for mortality, complications, length of stay, and reinterventions. OSR was performed in 25 (29%) and 61 (71%) patients for descending thoracic and thoracoabdominal CTBAD, respectively. Median age was 57.0 years (interquartile range [IQR], 52.0-64.2 years), and median diameter was 6.0 cm (IQR, 5.0-6.9 cm). Fifty-nine patients (69%) were male. Eight (9%) were treated for rupture. Follow-up duration was 4.6 years (IQR, 2.8-6.9 years). Hospital mortality occurred in five patients (5.8%). Cardiopulmonary bypass was used in 83 patients (97%) and deep hypothermic arrest in 36 (42%). Two patients (2.3%) each developed paraplegia, stroke, and renal failure requiring permanent hemodialysis in the postoperative period. Length of stay was 13.5 days (IQR, 10.0-21.0 days). Univariate predictors of hospital death included redo operations and prolonged pump time (P < .05). Six patients (7%) had aortic-related reoperations at 4.3 years (IQR, 2.7-5.2 years): one for an ascending aortic aneurysm and five for descending aortic aneurysms. Overall survival at 1, 5, and 7 years was 92%, 83%, and 70%, respectively, and freedom from reoperation was 99%, 90%, and 86%, respectively. OSR of CTBAD is a durable option with low mortality. Patients requiring redo operations or anticipated prolonged pump time need further evaluation to determine whether conventional OSR or TEVAR, if feasible, is the optimal treatment option.


Stimulation of granulopoiesis by liver macrophages.
Isolated murine Kupffer cells or liver macrophages release high levels of colony-stimulating activity (CSA) necessary for the proliferation of granulocytic and mononuclear cell colonies in vitro. CSA was detected in media conditioned by Kupffer cells ata concemtration of 0.25 x 10'6 cells per millilter. Conditioned media from suspensions of unseparated liver did not stimulate colony formation and, in high concentrations,were inhibitory. CSA obtained from Kupffer cells was more active on a cell percell basis than CSA OBTAINED FROM LUNG OR PERITONEAL MACROPHAGES. These studies indicate that liver macrophages can also release CSA and further support the concept that the monocyte-macrophage system may play a role in the regulation of granulopoiesis.


Characterization of ginseng saponins using electrospray mass spectrometry and collision-induced dissociation experiments of metal-attachment ions.
Electrospray mass spectrometry (ESMS) and collision-induced dissociation (CID) methodologies have been developed for the structural characterization of ginseng saponins (ginsenosides). Ginsenosides are terpene glycosides containing a triterpene core to which one to four sugars may be attached. They are neutral molecules which readily form molecular metal-attachment ions in positive ion ESMS experiments. In the presence of ammonium hydroxide intense deprotonated ions are generated. Both positive and negative ion ESMS experiments were found to be useful for molecular mass and structure determination of ten ginsenoside standards. Negative ion experiments made possible the determination of the molecular mass of each ginsenoside standard, the mass of the triterpene core and the masses and sequences of the sugar residues. Positive ion ESMS experiments with the alkali metal cations Li+ or Na+ and the transition metal cations Co2+, Ni2+ and Zn2+ were also useful in determining molecular masses. These alkali and transition metal cations form strongly bonded attachment ions with the ginsenosides. As a result, the CID mass spectra of the metal attachment ions show a variety of (structure characteristic) fragmentations. These experiments can be used to determine the identity of the triterpene core, the types and attachment points of sugars to the core and the nature of the O-glycosidic linkages in the appended disaccharides. Combining the results from the negative and positive ion experiments provides a promising approach to the structure analysis of this class of natural products.


Breast feeding and intergenerational social mobility: what are the mechanisms?
To investigate the association between breast feeding and intergenerational social mobility and the possible mediating role of neurological and stress mechanisms. Secondary analysis of data from the 1958 and the 1970 British Cohort Studies. Longitudinal study of individuals born in Britain during 1 week in 1958 and 1970. 17 419 individuals participated in the 1958 cohort and 16 771 in the 1970 cohort. The effect of breast feeding on intergenerational social mobility from age 10/11 to age 33/34 was analysed after multiple imputations to fill in missing data and propensity score matching on a wide range of confounders measured in childhood (1958 cohort N=16 039-16 154; 1970 cohort N=16 255-16 361). Own Registrar General's Social Class (RGSC) at 33/34 years adjusted for father's RGSC at 10/11 years, gender and their interaction. Breastfed individuals were more likely to be upwardly mobile (1958 cohort: OR 1.24 95% CI 1.12 to 1.38; 1970 cohort: OR 1.24 95% CI 1.12 to 1.37) and less likely to be downwardly mobile (1958 cohort: OR 0.81 95% CI 0.73 to 0.90; 1970 cohort: OR 0.79 95% CI 0.71 to 0.88). In an ordinal regression model, markers of neurological development (cognitive test scores) and stress (emotional stress scores) accounted for approximately 36% of the relationship between breast feeding and social mobility. Breast feeding increased the odds of upward social mobility and decreased the odds of downward mobility. Consistent with a causal explanation, the findings were robust to matching on a large number of observable variables and effect sizes were alike for two cohorts with different social distributions of breast feeding. The effect was mediated in part through neurological and stress mechanisms.


Modification of the Patient Competency Rating Scale to Measure Anosodiaphoria after Severe Acquired Brain Injury: Preliminary Findings.
Impaired self-awareness (ISA) of altered functional capacities is a common sequelae of severe acquired brain injury that can severely hamper neuro-rehabilitation in this clinical population. ISA is frequently associated with anosodiaphoria and/or apathy. Although several scales are available to measure apathy, no tools have been published to specifically assess anosodiaphoria after acquired brain injury. In this paper, we reported an initial effort to develop an anosodiaphoria subscale in a commonly used measure of ISA, that is, the Patient Competency Rating scale-neurorehabilitation form (PCRS-NR). A sample of 46 participants with severe acquired brain injury completed a functional, ISA, apathy, and anosodiaphoria assessment. One informal caregiver of each patient participated in the study. Thus, we were able to obtain external data on his/her level of functional competencies, and self-awareness, which allowed separating patients with low self-awareness (LSA) from those with high self-awareness (HSA). Finally, the patients were compared with 44 healthy age-gender-years of formal education matched control participants (HCs). Compared to both patients with HSA and HCs, patients with LSA demonstrated greater anosodiapvhoria and lower levels of functioning than both HSA patients and HCs. A stronger relationship emerged between ISA and anosodiaphoria rather than with apathy. These initial findings provide support that PCRS scale can be adapted to measure anosodiaphoria as well as ISA. The findings reveal a stronger correlation between this measure of anosodiaphoria and ISA compared with the correlation of apathy to ISA. The present method for measuring anosodiaphoria takes into account the actual levels of patients' functioning.


[The organization of the rehabilitation of children with the after-effects of perinatal pathology of nervous system in the conditions of day-stay hospital].
The new organizational pattern of hospital-substituting technology--the day-stay hospital for the rehabilitation of the children suffering from chronic somatic diseases and after-effects of perinatal lesion of the central nervous system. This approach gives an opportunity to implement a relevant and up-to-date neuro-somatic approach using the potential of medical specialists from the pediatric polyclinic's staff The priority is given to the non-pharmaceutical techniques of rehabilitation to permitting to come about the higher results even without expensive pharmaceuticals.


A proposed method for the relative quantification of levels of circulating microRNAs in the plasma of gastric cancer patients.
Gastric cancer (GC) is the fifth most common type of malignancy and the third leading cause of cancer-associated mortality worldwide. It is necessary to identify novel methods aimed at improving the early diagnosis and treatment of GC. MicroRNA expression profiles in the plasma of patients with GC have demonstrated a potential use in the opportune diagnosis of this neoplasm. However, there are currently no standardized targets for use in the normalization of microRNA Cq values for different neoplasms. The present study tested two normalization approaches while analyzing plasma derived from patients with GC and non-atrophic gastritis. The first method utilized a panel of small nucleolar RNAs (snoRNAs) and a small nuclear RNA (snRNA) provided by a commercial array. The second normalization approach involved the use of hsa-miR-18a-5p and hsa-miR-29a-3p, which were identified by a stability analysis of the samples being tested. The results revealed that the snoRNAs and snRNA were not expressed in all samples tested. Only the stable microRNAs allowed a narrow distribution of the data and enabled the identification of specific downregulation of hsa-miR-200c-3p and hsa-miR-26b-5p in patients with GC. hsa-miR-200c-3p and hsa-miR-26b-5p have been previously linked to cancer, and a Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that these microRNAs were associated with cell adhesion, cell cycle and cancer pathways.


Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation.
Medulloblastoma is the most common malignant brain tumor in children, and approximately seventy percent of average-risk patients will achieve long-term survival. Craniospinal irradiation (CSI), combined with chemotherapy and surgery, is currently the mainstay of treatment but places children who survive at risk for serious neurocognitive sequelae. These sequelae are intensified with a younger age at treatment, greater elapsed time following treatment, and an increased radiation dose. Many newer treatment approaches have attempted to address this problem by reducing the dose of the CSI component of radiation therapy while maintaining the current survival rates. This study evaluates longitudinal MR imaging during therapy to assess the impact of the two CSI doses (conventional [36 Gy] and reduced [23.4 Gy]) on normal appearing white matter volumes (NAWMV) evaluated in a single index slice. Twenty-six children and young adults at least three years of age enrolled on an institutional protocol for newly diagnosed, previously untreated primary medulloblastoma had at least four MR examinations over a minimum nine month period following CSI. These serial volumes were evaluated as a function of time since CSI in three analyses: 1) all subjects, 2) subjects stratified by age at CSI, and 3) subjects stratified by CSI dose. The first analysis demonstrated that medulloblastoma patients treated with CSI have a significant loss of NAWMV in contradistiction to normally expected maturation. Stratifying the patients by age at CSI found no significant differences in the rate of NAWMV loss. The final analysis stratified the patients by CSI dose and revealed that the rate of NAWMV loss was 23% slower in children receiving reduced-dose. Serial quantitative MR measures of NAWMV may provide a neuroanatomical substrate for assessing functional impact of CSI on normal brain function following treatment for medulloblastoma.


Loss of the tumor suppressor Hace1 leads to ROS-dependent glutamine addiction.
Cellular transformation is associated with altered glutamine (Gln) metabolism. Tumor cells utilize Gln in the tricarboxylic acid (TCA) cycle to maintain sufficient pools of biosynthetic precursors to support rapid growth and proliferation. However, Gln metabolism also generates NADPH, and Gln-derived glutamate is used for synthesis of glutathione (GSH). As both NADPH and GSH are antioxidants, Gln may also contribute to redox balance in transformed cells. The Hace1 E3 ligase is a tumor suppressor inactivated in diverse human cancers. Hace1 targets the Rac1 GTPase for degradation at Rac1-dependent NADPH oxidase complexes, blocking superoxide generation by the latter. Consequently, loss of Hace1 increases reactive oxygen species (ROS) levels in vitro and in vivo. Given the link between Hace1 loss and increased ROS, we investigated whether genetic inactivation of Hace1 alters Gln metabolism. We demonstrate that mouse embryonic fibroblasts (MEFs) derived from Hace1(-/-) mice are highly sensitive to Gln withdrawal, leading to enhanced cell death compared with wild-type (wt) MEFs, and Gln depletion or chemical inhibition of Gln uptake blocks soft agar colony formation by Hace1(-/-) MEFs. Hace1(-/-) MEFs exhibit increased Gln uptake and ammonia secretion, and metabolic labeling using (13)C-Gln revealed that Hace1 loss increases incorporation of Gln carbons into the TCA cycle intermediates. Gln starvation markedly increases ROS levels in Hace1(-/-) but not in wt MEFs, and treatment with the antioxidant N-acetyl cysteine or the TCA cycle intermediate oxaloacetate efficiently rescues Gln starvation-induced ROS elevation and cell death in Hace1(-/-) MEFs. Finally, Gln starvation increases superoxide levels in Hace1(-/-) MEFs, and NADPH oxidase inhibitors block the induction of superoxide and cell death by Gln starvation. Together, these results suggest that increased ROS production due to Hace1 loss leads to Gln addiction as a mechanism to cope with increased ROS-induced oxidative stress.


Development of a Novel Telemedicine Tool to Reduce Disparities Related to the Identification of Preschool Children with Autism.
The wait for ASD evaluation dramatically increases with age, with wait times of a year or more common as children reach preschool. Even when appointments become available, families from traditionally underserved groups struggle to access care. Addressing care disparities requires designing identification tools and processes specifically for and with individuals most at-risk for health inequities. This work describes the development of a novel telemedicine-based ASD assessment tool, the TELE-ASD-PEDS-Preschool (TAP-Preschool). We applied machine learning models to a clinical data set of preschoolers with ASD and other developmental concerns (n = 914) to generate behavioral targets that best distinguish ASD and non-ASD features. We conducted focus groups with clinicians, early interventionists, and parents of children with ASD from traditionally underrepresented racial/ethnic and linguistic groups. Focus group themes and machine learning analyses were used to generate a play-based instrument with assessment tasks and scoring procedures based on the child's language (i.e., TAP-P Verbal, TAP-P Non-verbal). TAP-P procedures were piloted with 30 families. Use of the instrument in isolation (i.e., without history or collateral information) yielded accurate diagnostic classification in 63% of cases. Children with existing ASD diagnoses received higher TAP-P scores, relative to children with other developmental concerns. Clinician diagnostic accuracy and certainty were higher when confirming existing ASD diagnoses (80% agreement) than when ruling out ASD in children with other developmental concerns (30% agreement). Utilizing an equity approach to understand the functionality and impact of tele-assessment for preschool children has potential to transform the ASD evaluation process and improve care access.


Expression profiles of schizophrenia susceptibility genes during human prefrontal cortical development.
Disruption in normal development of the human prefrontal cortex (PFC) may lead to cognitive dysfunction that manifests in individuals with schizophrenia. We sought to identify genes associated with age that are implicated in schizophrenia. We generated genome-wide expression profiles for the PFCs of humans ranging in age from 1 month to 49 years using the Affymetrix HG-U133 plus 2.0 microarrays (54 675 transcripts). Based on the criteria of significance (false discovery rate [FDR]-adjusted q < 0.001 and r(2) > 0.6), we identified the genes associated with age in the PFC. We then performed functional annotation analyses of age-associated genes using the Gene Ontology and the Genetic Association Database (GAD). We found robust age-dependent changes in gene expression in the PFCs of humans (2281 transcripts). The GAD analysis revealed that schizophrenia was an over-represented disease class, with 42 susceptibility genes included (p < 0.001, fold enrichment = 1.66, FDR = 1.5%). Among the 42 genes, glutamate receptor genes (GRIA1, GRIK1, GRIK2, GRIN2D, GRIP1, GRM5, GRM7 and SLC1A6) were consistently downregulated across age. We confirmed microarray gene expression changes by the quantitative polymerase chain reaction experiment. Although numerous genes undergo robust changes in expression during the PFC development, some of the changes may be confounded by known and unknown factors that are intrinsic to the postmortem brain studies. Multiple schizophrenia susceptibility genes undergo age-dependent expression changes in the human PFC, and any disruption in those genes during the critical period of development may predispose the individuals to schizophrenia.


Simulation modeling of supported lipid membranes - a review.
Lipid membranes are of great importance for many biological systems and biotechnological applications. One method to gain a profound understanding of the dynamics in lipid membranes and their interaction with other system components is by modeling these systems by computer simulations. Many different approaches have been undertaken in this endeavor that have led to molecular level insights into the underlying mechanisms of several experimental observations and biological processes with an extremely high temporal resolution. As compared to the free-standing lipid bilayers, there are fewer simulation studies addressing the systems of supported lipid membranes. Nevertheless, these have significantly enhanced our understanding of the behavior of lipid layers employed in applications spanning from biosensors to drug delivery and for biological processes such as the breathing cycle of lung surfactants. In this review, we give an account of the state of the art of methods and applications of the simulations of supported lipid bilayers, interfacial membranes at the air/water interface and on solid surfaces.