Bystanders' Victim Blaming and Minimizing Consequences of Weight-Based Cyberhate Attacks: The Roles of anti-Fat Attitudes, Body-Positive Online Content, and Gender.
Physical appearance and, specifically, weight are common reasons for cyberhate attacks among adolescents. Using a between-subject experimental design, this study focuses on the bystanders of such attacks on Instagram. We investigate bystanders' assessments in the form of two moral disengagement (MD) mechanisms-victim blaming and minimizing consequences-and we compare the assessments of attacks that are diversified by the victim's weight (i.e., a victim who is plus-size and a victim who is thinner). We also examine the moderating roles of bystanders' prejudice against people who are plus-size in the form of the so-called anti-fat attitudes, their frequency of viewing body-positive online content, and gender. The study's data come from an online survey conducted in 2020 with a representative sample of 658 Czech adolescents, aged 13-18. We tested our hypotheses with structural equation modeling. The results show that the two MD mechanisms work differently. The victim's displayed weight affected the bystanders' tendency to victim blame: adolescents blamed the victim who is plus-size more than the victim who is thinner, but the victim's weight made no difference in minimizing the consequences of the incident. A moderating effect for anti-fat attitudes and gender was found for victim blaming. Bystanders with higher anti-fat attitudes and boys blamed the victim who is plus-size more than the victim who is thinner. On the other hand, there was no effect for the frequency of viewing body-positive online content for either of the MD mechanisms. The results are discussed with regard to the differences between the two mechanisms and the practical implications for educational and prevention programs for youth.


Infection control in clinical placements: experiences of nursing and midwifery students.
This paper is a report of a study of the experiences of nursing and midwifery students in relation to infection control in their clinical placements and how these affect their learning. Compliance with infection control precautions has been found to be low in many areas. Reasons for non-compliance include factors relevant to nursing and midwifery students, such as lack of knowledge and lack of a positive role model. However, there is little in the literature about how students experience infection control in placements and how this affects their own practice. Semi-structured interviews were undertaken in 2009 with 40 nursing and midwifery students. Analysis of transcripts was by Framework analysis. Students identified practices that they had observed and benchmarked these against what they had been taught at university and what was demonstrated by staff perceived as positive role models. Observing inappropriate practice affected student practice both positively and negatively. Students were reluctant to report poor practice due to fear of failing placements and not wanting to be identified negatively by staff. Students believed that practice supported by theory was important to provide them with a rationale for their activities and to support any complaints that they had. Poor practice in clinical placements can have a negative impact on student learning and practice and may therefore have implications for the practice of future nurses and midwives. In order to maintain patient safety, there needs to be more support for students who wish to identify poor practice.


Auto-tuning numerical method for acoustic wave simulation using analytical solution.
Numerical wavefield simulation such as commercial simulation software enables an optimal design of an ultrasound computed tomography (USCT) system for clinical purpose of before prototyping. Such simulator, not developed for optimal design though, can provide rapid implementation for acoustic wave propagation but may lead to unexpected errors during the establishment of numerical model. Here, we propose an auto-tuning numerical method (ATNM), aiming to optimize physical parameters (e.g. grid size, Courant-Friedrichs-Lewy (CFL) number, perfectly matched layer (PML) absorption coefficient, etc) such that the enumerated wavefield computed on those converges to the corresponding analytical solution derived from acoustic scattering theory. We use genetic algorithm (GA) to automatically calibrate numerical wavefield. Our preliminary test is to investigate the best design of PML absorption coefficient for USCT to minimize mean relative error (MRE) between the k-Wave simulation and the analytic model and show its efficacy. The experimental results verify our hypothesis that this calibrated numerical simulator on a simple physical domain is generalizable to any other domains.


Age and performance at fledging are a cause and consequence of juvenile mortality between life stages.
Should they stay or should they leave? The age at which young transition between life stages, such as living in a nest versus leaving it, differs among species and the reasons why are unclear. We show that offspring of songbird species that leave the nest at a younger age have less developed wings that cause poorer flight performance and greater mortality after fledging. Experimentally delayed fledging verified that older age and better developed wings provide benefits of reduced juvenile mortality. Young are differentially constrained in the age that they can stay in the nest and enjoy these fitness benefits because of differences among species in opposing predation costs while in the nest. This tension between mortality in versus outside of the nest influences offspring traits and performance and creates an unrecognized conflict between parents and offspring that determines the optimal age to fledge.


A light at the end of the tunnel - from mutation identification to a potential treatment for Alzheimer's disease.
Recent advances have driven the development of immunotherapies that act by either promoting or suppressing a patient's immune system to treat inflammation, autoimmune disease, cardiovascular disease, infectious diseases, and several cancers. In addition, research conducted over the past 25 years has identified therapeutic targets and indicated that immunotherapy could be used to treat Alzheimer's disease (AD). Despite a number of setbacks, this approach has now led to the development of the first disease-modifying treatments for this devastating disease. A key neuropathological feature of AD is the accumulation of a ~40-amino acid peptide known as amyloid β (Aβ) in the brain and cerebrovasculature. Our detection of an Aβ precursor protein mutation that caused early-onset AD in a Swedish family by enhancing Aβ protofibril formation sharpened the focus on soluble Aβ aggregates (oligomers and protofibrils) as viable therapeutic targets. Initial studies developed and tested a mouse monoclonal antibody (mAb158) with specific conformation-dependent binding to these soluble Aβ aggregates. Treatment with mAb158 selectively reduced Aβ protofibrils in the brain and cerebrospinal fluid of a transgenic mouse model of AD. A humanized version of mAb158 (lecanemab) subsequently entered clinical trials. Based on promising Phase 2 data showing plaque clearance and reduced cognitive decline, a Phase 3 trial found that lecanemab slowed decline on the primary cognitive endpoint by 27% over 18 months and also produced positive effects on secondary clinical endpoints and key biomarkers. In July 2023, the FDA granted lecanemab a full approval, and this therapeutic antibody will be marketed as Leqembi®. This represents a significant advance for patients with AD, although many challenges remain. In particular, it is now more important than ever to identify individuals who are vulnerable to AD, so that treatment can be initiated at an early stage in the disease process.


Analysis of NKp30/NCR3 isoforms in untreated HIV-1-infected patients from the ANRS SEROCO cohort.
Natural killer (NK) cells play a prominent role at the intersection between innate and cognate immunity, thus influencing the development of multiple pathological conditions including HIV-1-induced AIDS. Not only NK cells directly kill HIV-1-infected cells, but also control the maturation and/or elimination of dendritic cells (DCs). These functions are regulated by the delicate balance between activating and inhibiting receptors expressed at the NK-cell surface. Among the former, NKp30 has raised significant interest since the alternative splicing of its intracellular domain leads to differential effector functions, dictating the prognosis of patients bearing gastrointestinal sarcoma, and B7-H6 has recently been identified as its main ligand. Since NKp30 is downregulated in CD56-/CD16+ NK cells expanded in viremic, chronically infected HIV-1+ patients, we decided to investigate the predictive value of NKp30 splice variants for spontaneous disease progression in 89 therapy-naïve HIV-1-infected individuals enrolled in an historical cohort of patients followed since diagnosis (ANRS SEROCO cohort). We found no difference in the representation of NK-cell subsets (CD56bright, CD56dim, CD56neg) in HIV-1-infected patients as compared with healthy subjects. NKp30 downregulation was detected in CD56dim and CD56neg NK-cell subsets, yet this did not convey any prognostic value. None of the NKp30 isoforms did affect disease progression, as measured in terms of time-to-loss of circulating CD4+ T cells, time-to-AIDS-defining events and overall survival. NKp30 isoforms do not seem to play a major role in the outcome of HIV-1 infection, but the heterogeneity of the immuno-virological status of patients at enrollment could have to be taken into account.


Description of a new species of Maritrema (Digenea:Microphallidae) from Mar Chiquita coastal lagoon (Buenos Aires, Argentina) with notes on its life cycle.
Adults of Maritrema bonaerensis n. sp. (Digenea:Microphallidae) were collected from the intestine of the gulls Larus maculipennis and Larus atlanticus from Mar Chiquita coastal lagoon, Buenos Aires province, Argentina. The new species differs from M. pulcherrima Travassos, 1928 in having smaller sucker ratio, longer intestinal ceca, ovary not lobed, and larger eggs, and from Maritrema prosthometra Deblock and Heard, 1969 it differs in having larger suckers, smaller vitelline follicles, and in the absence of pars prostatica. It differs from Maritrema acadiae (Swales, 1933) in having larger body and pharynx and longer cirrus. It differs from Maritrema paracadiae Ching, 1974 in the larger pharynx, longer cirrus, and in the absence of prominent prostatic cells. From Maritrema majestova Ke, 1976, it differs in having a larger body, smaller eggs, and a long and protusible cirrus. Finally, M. bonaerensis differs from Maritrema chiricae Deblock, 1975 in the larger body, longer cirrus, and in the morphology of the seminal vesicle. Sporocysts and metacercarial stages isolated from the snail Heleobia australis australis and from the crabs Cyrtograpsus angulatus and Chasmagnatus granulata, respectively, suggest that those invertebrates could act as intermediate host in the life cycle of the new species in the lagoon. This assumption is supported by evidence derived from natural and experimental infections, from studies on biology of the actual and presumed hosts, as well as from previous reports on life cycles of species of Maritrema with similar transmission patterns.


Growth rates of Actinomyces viscosus and Streptococcus mutans during early colonization of tooth surfaces in gnotobiotic rats.
Germfree Osborne-Mendel rats were monoassociated with Actinomyces viscosus or Streptococcus mutans. The adherence and subsequent growth of these organisms on the tooth surface was studied by means of total viable cell counts. Both A. viscosus and S. mutans showed a lag phase and an exponential growth phase, similar to logarithmic growth in batch cultures. The exponential growth rates of S. mutans and A. viscosus were 0.63 h-1 (doubling time [td] = 1.1 h) and 0.24 h-1 (td = 2.9 h), respectively. After a period of rapid growth, the rate declined and the populations approached a steady state. The presence of a sucrose-containing diet did not significantly influence the exponential growth rates of A. viscosus and S. mutans, but had a slight negative effect on the initial adherence of S. mutans at the tooth surface.


Metagonimiasis in Korea.
Of the intestinal trematode infections in Korea, metagonimiasis is the most important under public health aspects. In a nationwide survey in 1981, at least 450,000 people (1.2%) were found infected. The endemic areas are scattered along rivers which run to the southern and eastern coast, where more than 20% of villagers are commonly infected. The snail hosts of Metagonimus yokogawai are either Semisulcospira spp. or Koreanomelania spp. The fish hosts are sweetfish (Plecoglossus altivelis) and many species of cyprinid fish, of which the former is the more important source of infection. Dog, cat and rat are found naturally infected in endemic areas. Sweetfish frequently have more than 10,000 metacercariae in their muscles. In autumn, the metacercarial burden reaches its zenith, when the fish is sweetest. Eating only one raw sweetfish may result in severe abdominal pain, prostration and watery diarrhoea, However, in endemic areas, many egg discharging cases rarely suffer from diarrhoea and abdominal pain. The symptoms seem mainly to depend on the degree of infection. But also duration of infection seems to be a factor which determines the intensity of symptoms. In experimental infection of cat or dog, juvenile worms thrive into crypts of Lieberkühn in the jejunum for about 5 days. Thereafter, the adults move to the intervillous space and destroy the enterocytes. Adults rarely reach the submucosa or lymphatic tissues. In rather heavy infection, mucosal damage such as villi fusion, villi shortening, slight hypertrophy of crypts, goblet cell depletion, inflammatory cell infiltration and shortening of microvilli were observed. These pathologic findings regress within 4 weeks of infection though adult worms still live in the mucosa.


Impact of a brief intervention on physical activity and social cognitive determinants among working mothers: a randomized trial.
Working mothers exhibit high levels of inactivity, and theory-based interventions to bolster physical activity within this population are needed. This study examined the effectiveness of a brief social cognitive theory-based intervention designed to increase physical activity among working mothers. Participants (N = 141) were randomly assigned to an intervention only, intervention plus follow-up support, or waitlist control condition. The intervention consisted of two group-based workshop sessions designed to teach behavior modification strategies using social cognitive theory. Data were collected at baseline, immediately post-intervention, and 6-month follow-up. Results showed intervention participants exhibited short-term increases in physical activity, which were partially maintained 6 months later. Improvements in physical activity were mediated by increases in self-regulation and self-efficacy. This study provides some support for the effectiveness of a brief intervention to increase physical activity among working mothers. Future programs should explore alternative support mechanisms which may lead to more effective maintenance of initial behavior changes.


BAC library resources for map-based cloning and physical map construction in barley (Hordeum vulgare L.).
Although second generation sequencing (2GS) technologies allow re-sequencing of previously gold-standard-sequenced genomes, whole genome shotgun sequencing and de novo assembly of large and complex eukaryotic genomes is still difficult. Availability of a genome-wide physical map is therefore still a prerequisite for whole genome sequencing for genomes like barley. To start such an endeavor, large insert genomic libraries, i.e. Bacterial Artificial Chromosome (BAC) libraries, which are unbiased and representing deep haploid genome coverage, need to be ready in place. Five new BAC libraries were constructed for barley (Hordeum vulgare L.) cultivar Morex. These libraries were constructed in different cloning sites (HindIII, EcoRI, MboI and BstXI) of the respective vectors. In order to enhance unbiased genome representation and to minimize the number of gaps between BAC contigs, which are often due to uneven distribution of restriction sites, a mechanically sheared library was also generated. The new BAC libraries were fully characterized in depth by scrutinizing the major quality parameters such as average insert size, degree of contamination (plate wide, neighboring, and chloroplast), empty wells and off-scale clones (clones with <30 or >250 fragments). Additionally a set of gene-based probes were hybridized to high density BAC filters and showed that genome coverage of each library is between 2.4 and 6.6 X. BAC libraries representing >20 haploid genomes are available as a new resource to the barley research community. Systematic utilization of these libraries in high-throughput BAC fingerprinting should allow developing a genome-wide physical map for the barley genome, which will be instrumental for map-based gene isolation and genome sequencing.


Surgical treatment of spasticity by selective posterior rhizotomy: 30 years experience.
Spasticity is a common neurologic disorder with adverse effects on the patient's function. Conservative management is unsuccessful in a significant proportion of patients and neurosurgical intervention should be considered. The mainstay of surgical treatment of spasticity is selective posterior rhizotomy, i.e., section of sensory nerve roots of the cauda equina. To report our experience with selective posterior rhizotomy in the treatment of spasticity. We retrospectively reviewed our experience in 154 patients who underwent SPR during 30 years. The indication for surgery was spasticity that significantly hindered the patient's function or care and was resistant to conservative treatment. All patients were evaluated for spasticity in the lower and upper limbs, the presence or absence of painful spasms, and sphincter disturbances. The decision as to which roots to be sectioned, and to what extent, was based mainly on clinical muscle testing. Reduction of spasticity in the lower limbs was obtained in every case, with improvement in movements in 86% of cases. Painful spasms were alleviated in 80% of cases. Amelioration of neurogenic bladder was observed in 42%. A minority of the patients also showed improvement in speech and cognitive performance. There was no perioperative mortality or major complications. SPR is a safe and effective method for the treatment of spasticity with long-lasting beneficial effects. We suggest that this method be considered more frequently for patients with spasticity that interferes with their quality of life.


Primary tumor resection improves the survival of younger patients with metastatic breast cancer.
Current treatments for metastatic breast cancer (MBC) include palliation with chemotherapy and/or hormone therapy, neither of which has the effect of adequately improving survival. Local surgery to remove the primary breast tumor is performed to improve local control and prevent uncontrolled chest wall disease (UCD). From June 1962 to February 2007, 344 patients with MBC were treated at National Cancer Center Hospital. In our review of these cases, we evaluated the prognostic impact of local surgery and other clinicopathological features. One hundred and sixty patients (47%) underwent resection of primary breast tumor, while 184 (53%) patients were treated without surgery. Overall survival (OS) was prolonged in patients treated with surgery (p=0.049), younger patients (age <50, p=0.023), and patients with bone or soft tissue metastases (p=0.013). While surgery significantly improved OS in young patients (p=0.021), it did not increase OS in older patients (age >51, p=0.665) or patients with visceral metastasis (p=0.797). This study demonstrated that local surgery improved OS of patients with MBC; local surgery should therefore be considered, especially in young patients. Prospective studies are required to validate these findings and evaluate the impact of surgical intervention.


[Mitochondrial disfunction in Parkinson's disease].
Mitochondrial structural and functional abnormalities in Parkinson's disease and experimental animal models of this pathology are described. Special attention is paid to the inactivation of mitochondrial enzymes, mutations in mitochondrial and nuclear DNA, and genomic and proteomic research of mitochondrial proteins in Parkinson's disease and experimental parkinsonism of animals.


Hematocrit and Serum Hemoglobin Do Not Influence Values in Computed Tomography Perfusion of Patients With Acute Ischemic Stroke.
There is a correlation between both serum hemoglobin (HGB) and hematocrit (HCT) and attenuation values of vessels in noncontrast-enhanced computed tomography (NECT), which could influence calculated perfusion maps in CT perfusion. We retrospectively included 45 patients, who presented with acute new neurological symptoms and underwent NECT and CT perfusion (128-row multi detector scanner, coverage: 6.9 cm craniocaudally; 80 kV; 200 mAs; temporal resolution: 2 seconds using 40 mL Ultravist 370 at a flow rate of 5 mL/s) on admission and a follow-up MRI within 1 week of admission. Hematocrit, HGB, and attenuation values did not differ between patients with stroke and controls. A statistically significant correlation was found between HCT and HGB and attenuation values in the internal carotid artery or middle cerebral artery on NECT (P < 0.05). No statistically significant correlation was observed between HCT and HGB and perfusion maps. Hematocrit and HGB do not influence calculated perfusion maps. There is no need for HCT/HGB-adjusted cerebral blood volume thresholds in stroke patients.


Characteristics of postictal generalized EEG suppression in children.
Although the pathophysiologic mechanism of sudden unexpected death in epilepsy (SUDEP) is unknown, autonomic dysfunction is thought to be the most likely. It has been hypothesized that respiratory depression resulting in SUDEP may be secondary to postictal generalized electroencephalography suppression (PGES). We sought to determine the characteristics of PGES in children. This included whether PGES was associated with ictally mediated autonomic changes and potential increased risk of SUDEP. Children admitted to our Pediatric Epilepsy Monitoring Unit between 3/2009 and 10/2011 were prospectively recruited. Clinical and electrophysiological data from children with PGES were compared to those without PGES. Data included the occurrence of peri-ictal tachycardia, bradycardia, and hypoxemia. Potential SUDEP risk was assessed using SUDEP-7 Inventory scores. Thirty seven children with 168 seizures were analyzed. PGES was observed following 27/168 (16.1%) seizures in 12/37 (32.4%) children. Only primary and secondarily generalized tonic clonic seizures were marked by PGES. PGES was significantly associated with peri-ictal tachycardia (p=0.019) and hypoxemia (p=0.005). Children with PGES had significantly higher SUDEP-7 Inventory scores than those without PGES (4.2 ± 1.3 versus 2.8 ± 1.4, p=0.007). SUDEP-7 scores were not significantly different between children with and without peri-ictal tachycardia (3.4 ± 1.3 versus 2.5±1.6, p=0.12), bradycardia (4 ± 2 versus 2.9 ± 1.4, p=0.45), or hypoxemia (3.4 ± 1.5 versus 2.4 ± 1.3, p=0.051). Based on our data, PGES is not rare in children. Children with PGES may be at greater risk for SUDEP as measured by the SUDEP-7 Inventory.


Egg marketing in national supermarkets: egg quality--part 1.
Two surveys were conducted to determine the quality of eggs offered to consumers in large supermarkets in various regions of the US. The first survey was conducted in California (CA) in 1994 and included 38 samples of large (L) and extra large (XL) white eggs in 15 markets. Individual eggs were weighed, candled, and broken out for Haugh unit (HU) determination. Regional differences in age of eggs, the number of eggs below 55 HU, and the percentage of cracked eggs were observed. The second survey was conducted in California (CA), Illinois (IL), Pennsylvania (PA), Texas (TX), North Carolina (NC), and New England (NE). This study included brown and white eggs and samples from 115 stores in 38 cities. Significant age, egg weight, HU, and cracked egg differences were observed between states. Brown and white eggs were different relative to age and HU, but egg weights and cracked eggs were statistically the same. The two surveys, 1994 and 1996, within CA demonstrated very similar measurements when L-white eggs were compared.


Differentiation of neural stem cells influences their chemotactic responses to vascular endothelial growth factor.
Although much effort has been devoted to the delineation of factors involved in the migration of neural stem/progenitor cells (NSCs), the relationship between the chemotactic response and the differentiation status of these cells remains elusive. In the present study, we found that NSCs in varying differentiation states possess different chemotactic responses to vascular endothelial growth factor (VEGF): first, the number of chemotaxing NSCs and the optimal concentrations of VEGF that induced the peak migration vary greatly; second, time-lapse video analysis shows that NSCs at certain differentiation states migrate more efficiently toward VEGF, although the migration speed remains unchanged irrespective of cell states; third, the phosphorylation status of Akt, ERK1/2, SAPK/JNK, and p38MAPK is closely related to the differentiation levels of NSCs subjected to VEGF; and, finally, although inhibition of ERK1/2 signaling significantly attenuates VEGF-stimulated transfilter migration of both undifferentiated and differentiating NSCs, NSCs show normal chemotactic response after treatment with inhibitors of SAPK/JNK or p38MAPK. Meanwhile, interference with PI3K/Akt signaling prevents only NSCs of 12 hr differentiation, but not NSCs of 1 day or 3 days differentiation, from migrating in response to VEGF. Moreover, blocking of PI3K/Akt or MAPK signaling impairs the migration efficiency and/or speed, the extent of which depends on the cell differentiation status. Collectively, these results demonstrate that differentiation of NSCs influences their chemotactic responses to VEGF: NSCs in varying differentiation states have different migratory capacities, thereby shedding light on optimization of the therapeutic potential of NSCs to be employed for neural regeneration after injury.


The effect of centrifugation on the fracture properties of acrylic bone cements.
In this study, centrifugation did not alter the static or cyclic fracture properties of bone cement. Tests of fracture toughness and fatigue-crack propagation of centrifuged specimens of commercial cements (with and without antibiotic additions) demonstrated no significant difference from control values. Among the cements tested, Palacos (with and without antibiotic) was found to have a significantly higher fracture toughness than either Simplex or Zimmer. We attributed this difference in fracture toughness to the higher molecular weight measured for the Palacos cements. For the tested cements, only Simplex had a significantly greater volume contraction on setting due to centrifugation. The results of our study demonstrate that centrifugation of bone cement does not improve the cement's resistance to fracture in the presence of surface imperfections, such as those found at the bone-cement interface.


Mechanism and outcomes of catheter ablation for ventricular tachycardia in adults with repaired congenital heart disease.
Repaired congenital heart disease (rCHD) is strongly associated with ventricular tachycardia (VT) as an important late cause of morbidity and mortality. Ventricular reentry most commonly includes anatomic isthmuses created during the repair procedures. The purpose of this study was to analyze the long-term outcomes of catheter ablation, a commonly used standalone or adjunctive therapy, in a cohort of rCHD patients. A retrospective analysis of 21 consecutive patients with rCHD (45.0 ± 3.0 years, 71.4% male) undergoing ablation for VT was performed. The primary composite outcome was defined as in-hospital arrhythmic death, out-of-hospital sudden cardiac death, or appropriate implantable cardioverter-defibrillator therapy. At initial electrophysiologic study, 14 patients (66.7%) had reentrant VT through an electroanatomic isthmus; the remaining 7 patients (33.3%) demonstrated focal VT. Isthmus-dependent reentry was identified as the mechanism for VT in 14 patients (66.7%), and conduction block was confirmed in 8 of these patients (57.1%). No patients with confirmed block developed VT recurrence. During long-term follow-up (33 ± 7 months), 20 of 21 patients (95.2%) had not reached the primary composite outcome. Three patients died of nonarrhythmic causes. Catheter-based VT ablation in patients with rCHD is associated with a low rate of VT recurrence. Focal VT was not uncommon in this cohort. If a reentrant mechanism is present, confirmation of conduction block across the isthmus is vital to prevent recurrence.


Puerperal and cycloid psychoses. Results of a retrospective study.
Puerperal psychoses are traditionally considered to be nosologically unspecific. They are defined exclusively by their occurrence close to delivery. Attempts to further diagnostically subdivide puerperal psychoses have been prevented to date by the influence of Kraepelin's dichotomy. New possibilities of nosological differentiation arose out of Kasanin's (1933) description of schizoaffective psychoses and out of Leonhard's differentiated nosology (1986). The objective of the present, retrospective study was to apply Leonhard's nosology to 42 postpartal psychoses. Five diagnostic groups could be identified: 6 cases of manic-depressive disorder, 7 cases of pure depression, 8 cases of pure melancholia, 2 cases of unsystematic schizophrenia, and 19 cases of cycloid psychoses. For this reason we consider that the concept of the cycloid psychoses is appropriate for the characterization of a large proportion of childbed psychoses.


Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.
The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.


[Infectious mononucleosis in patients with inflammatory bowel disease under treatment with azathioprine].
The use of immunomodulators for the treatment of inflammatory bowel disease is increasing. One of the most common adverse effects associated with this kind of drugs are infectious complications. In recent years, special attention has been paid to certain latent infections which, in patients under immunomodulatory therapy, can be reactivated and prove lethal. Consequently, preventive actions have been adopted, such as screening for hepatitis B virus and tuberculosis infection before starting these treatments. Primary infection with the Epstein-Barr herpesvirus is usually asymptomatic. However, this virus can have an aggressive course and even lead to the development of lymphoma. We report two cases of atypical infectious mononucleosis in patients with inflammatory bowel disease under azathioprine therapy and review the available evidence on the most appropriate therapeutic approach in this subset of patients.


Sol-gel based sensor for selective formaldehyde determination.
We report the development of transparent sol-gels with entrapped sensitive and selective reagents for the detection of formaldehyde. The sampling method is based on the adsorption of formaldehyde from the air and reaction with beta-diketones (for example acetylacetone) in a sol-gel matrix to produce a yellow product, lutidine, which was detected directly. The proposed method does not require preparation of samples prior to analysis and allows both screening by visual detection and quantitative measurement by simple spectrophotometry. The detection limit of 0.03 ppmv formaldehyde is reported which is lower than the maximum exposure concentrations recommended by both the World Health Organisation (WHO) and the Occupational Safety and Health Administration (OSHA). This sampling method was found to give good reproducibility, the relative standard deviation at 0.2 and 1 ppmv being 6.3% and 4.6%, respectively. Other carbonyl compounds i.e. acetaldehyde, benzaldehyde, acetone and butanone do not interfere with this analytical approach. Results are provided for the determination of formaldehyde in indoor air.


[50 years of clinical trials; a new direction in medicine].
In 1998 the medical community commemorated the completion of the first truly randomised trial, the Medical Research Council Streptomycin Study. This invention is at least as important as Harrison's clocks, which in the 18th century solved the problem of measuring longitude at sea. Naturally the idea of randomised controls had evolved from previous notions. Obtaining informed consent remains essentially a matter between patient and physician, but in the meantime four other interested parties have joined in: governing bodies, the pharmaceutical industry, medical journals, and the mass media. In order to keep all these forces in check, lawmakers should protect the weakest parties against the more powerful ones. There is a great deal to be done in the next 50 years.


The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats.
Angelica sinensis (AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus.


Building a second brain in the bowel.
The enteric nervous system (ENS) is sometimes called the "second brain" because of the diversity of neuronal cell types and complex, integrated circuits that permit the ENS to autonomously regulate many processes in the bowel. Mechanisms supporting ENS development are intricate, with numerous proteins, small molecules, and nutrients that affect ENS morphogenesis and mature function. Damage to the ENS or developmental defects cause vomiting, abdominal pain, constipation, growth failure, and early death. Here, we review molecular mechanisms and cellular processes that govern ENS development, identify areas in which more investigation is needed, and discuss the clinical implications of new basic research.


Genetically engineered vaccines.
The application of recombinant DNA technology to allergen research has provided the sequence information and genetic material to produce new types of allergy vaccines. One general strategy has been to use the knowledge to produce synthetic peptides that represent selected T-cell or B-cell epitopes. The production of genetically engineered allergens provides an alternative strategy to construct hypoallergenic vaccines, which can provide a better and less selected representation of the epitopes. Many strategies have been used to produce such hypoallergens, and their ability to reduce allergenicity has been amply demonstrated by skin and nasal provocation tests. The retention of T cell-stimulating activity has also been demonstrated, and a consistent feature of the vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity, the ability to induce anti-allergen IgG antibody. The lead hypoallergens have been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1. A clinical trial with these medicaments has shown the ability to modify IgE and IgG antibody production, skin test reactivity, and symptom scores. This is the first trial of a recombinant allergy vaccine, and it has set a benchmark for further studies. A new generation of hypoallergens is now being produced based on the detailed knowledge of the tertiary structures of the allergens and of the T-cell and B-cell epitopes. The modifications have been made to change the topography of the allergens while retaining a stable, folding structure. In the case of Bet v 1, tertiary structures of hypoallergens have been determined. Structurally modeled hypoallergens have been produced for pollen, venom, food, and latex allergens, with promising characteristics from preclinical studies.


Dosage effects of X and Y chromosomes on language and social functioning in children with supernumerary sex chromosome aneuploidies: implications for idiopathic language impairment and autism spectrum disorders.
Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and pentasomy X/Y-aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning. Participants included 110 youth with X/Y-aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean ∼12 years; range 4-22) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the children's communication checklist-2 and the social responsiveness scale to assess language skills and autistic traits, respectively. Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language. Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y-aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders.


Grommets versus paracentesis in secretory otitis media. A prospective, controlled study.
One hundred and ninety-three consecutive children with bilateral secretory otitis media were treated by adenoidectomy, bilateral paracentesis, and evacuation of middle ear effusion, but with insertion of a grommet in the right ear only. At follow-up one to three years later, the audiometric and tympanometric results were similar in right and left ears. The primary advantage of grommet insertion was normalization of the hearing ability for as long as the grommet was functioning. Thus, only 1% of the ears with grommets had hearing losses exceeding 30 dB HL, whereas this occurred in about 20% of ears without grommets. The adverse effects of grommet insertion included periodic aural discharge during the functioning period of the grommet in 14% and tympanosclerosis of the drum in 48%. In the group of ears treated with paracentesis only, tympanosclerosis occurred in 10%. However, reinsertion of grommets was indicated in 10% of right ears, and 23% of left ears required grommets as well. Of the various pre- and perioperative factors analyzed, only a granulating mucous membrane and copious middle ear effusion could be correlated to frequent and protracted episodes of secretory otitis that required repeated treatment. The implications of these findings are discussed.


A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury.
Many diseases and pathological conditions are characterized by transient or constitutive overproduction of reactive oxygen species (ROS). ROS are causal for ischemia/reperfusion (IR)-associated tissue injury (IRI), a major contributor to organ dysfunction or failure. Preventing IRI with antioxidants failed in the clinic, most likely due to the difficulty to timely and efficiently target them to the site of ROS production and action. IR is also characterized by changes in the activity of intracellular signaling molecules including the stress kinase p38MAPK. While ROS can cause the activation of p38MAPK, we recently obtained in vitro evidence that p38MAPK activation is responsible for elevated mitochondrial ROS levels, thus suggesting a role for p38MAPK upstream of ROS and their damaging effects. Here we identified p38MAPKα as the predominantly expressed isoform in HL-1 cardiomyocytes and siRNA-mediated knockdown demonstrated the pro-oxidant role of p38MAPKα signaling. Moreover, the knockout of the p38MAPK effector MAPKAP kinase 2 (MK2) reproduced the effect of inhibiting or knocking down p38MAPK. To translate these findings into a setting closer to the clinic a stringent kidney clamping model was used. p38MAPK activity increased upon reperfusion and p38MAPK inhibition by the inhibitor BIRB796 almost completely prevented severe functional impairment caused by IR. Histological and molecular analyses showed that protection resulted from decreased redox stress and apoptotic cell death. These data highlight a novel and important mechanism for p38MAPK to cause IRI and suggest it as a potential therapeutic target for prevention of tissue injury.


[Endomorphines in schizophrenia].
The biological enigma of schizophrenia has led, on the basis of thin evidence, to widen the field of clinical research to a study of endomorphines in this disease. Too many different methods of measuring the levels of opiate peptides in the CSF have been used so that it is not possible to analyse the results statistically. Clinical trials of agonists and antagonists to the opiate receptors have once again emphasised the biochemical heterogeneity of schizophrenics but have not allowed any confirmation that the endorphinical system plays any part in the genesis or symptomatology of schizophrenia. The presence of sub-groups who respond positively to experimental treatment can lead to the hope, despite the uncertainties of their mode of pharmacological action, to the next advance in the routine treatment of schizophrenia.


Carbon gain, allocation and storage in rhizomes in response to elevated atmospheric carbon dioxide and nutrient supply in a perennial C3 grass, Phalaris arundinacea.
Reed canary grass (Phalaris arundinacea L.) is a fast-growing, perennial, rhizomatous C3 grass considered as a model invasive species for its aggressive behaviour. The same traits make it a candidate for bioenergy feedstock. We tested the following hypotheses: (1) elevated atmospheric [CO2] and nutrient supply enhance photosynthetic carbon acquisition of this fructan-accumulating grass with little or no photosynthetic downregulation; (2) elevated [CO2] promotes carbon allocation to growth when nutrients are sufficient and to fructan storage in rhizomes when nutrients are low. Plants were grown at ambient or elevated (+320μmolmol-1) [CO2], and fertilised using full or one-eighth strength modified Hoagland solution. We investigated leaf photosynthesis, whole-plant water use, biomass allocation, and nitrogen and carbon storage in rhizomes. Elevated [CO2] enhanced light-saturated net CO2 assimilation by 61%. It doubled whole-plant, stem and root biomass in summer. Plants grown in elevated [CO2] had a greater rate of CO2 assimilation at higher [CO2], indicating a shift in photosynthetic apparatus for enhanced carbon gain under elevated [CO2]. The majority of belowground biomass was allocated to rhizomes for storage rather than to roots in both seasons. In autumn, elevated [CO2] increased fructan concentration in rhizomes from 8.1 to 11.7% of biomass when nutrients were low (P=0.023). Our results suggest that elevated [CO2] combined with sufficient nutrients is likely to enhance carbon gain and growth of P. arundinacea, and to increase its productivity and competitiveness in summer. Elevated [CO2] is likely to enhance long-term fructan storage in rhizomes, which may benefit overwintering and vegetative spread.


Low-dimensional behavior of a Kuramoto model with inertia and Hebbian learning.
We study low-dimensional dynamics in a Kuramoto model with inertia and Hebbian learning. In this model, the coupling strength between oscillators depends on the phase differences between the oscillators and changes according to a Hebbian learning rule. We analyze the special case of two coupled oscillators, which yields a five-dimensional dynamical system that decouples into a two-dimensional longitudinal system and a three-dimensional transverse system. We readily write an exact solution of the longitudinal system, and we then focus our attention on the transverse system. We classify the stability of the transverse system's equilibrium points using linear stability analysis. We show that the transverse system is dissipative and that all of its trajectories are eventually confined to a bounded region. We compute Lyapunov exponents to infer the transverse system's possible limiting behaviors, and we demarcate the parameter regions of three qualitatively different behaviors. Using insights from our analysis of the low-dimensional dynamics, we examine the original high-dimensional system in a situation in which we draw the intrinsic frequencies of the oscillators from Gaussian distributions with different variances.


Real-World Effectiveness of PCSK9 Inhibitors in Reducing LDL-C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries.
Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow-up schedules were not prespecified and could vary, persistence and adherence as well as low-density lipoprotein cholesterol (LDL-C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid-lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL-C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6-month persistence and adherence to therapy were >85%, and LDL-C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL-C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH. Conclusions PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL-C-lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL-C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL-C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies.


Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia.
Upon cerebral hypoxia-ischemia (HI), apoptosis-inducing factor (AIF) can move from mitochondria to nuclei, participate in chromatinolysis, and contribute to the execution of cell death. Previous work (Cande, C., N. Vahsen, I. Kouranti, E. Schmitt, E. Daugas, C. Spahr, J. Luban, R.T. Kroemer, F. Giordanetto, C. Garrido, et al. 2004. Oncogene. 23:1514-1521) performed in vitro suggests that AIF must interact with cyclophilin A (CypA) to form a proapoptotic DNA degradation complex. We addressed the question as to whether elimination of CypA may afford neuroprotection in vivo. 9-d-old wild-type (WT), CypA(+/-), or CypA(-/-) mice were subjected to unilateral cerebral HI. The infarct volume after HI was reduced by 47% (P = 0.0089) in CypA(-/-) mice compared with their WT littermates. Importantly, CypA(-/-) neurons failed to manifest the HI-induced nuclear translocation of AIF that was observed in WT neurons. Conversely, CypA accumulated within the nuclei of damaged neurons after HI, and this nuclear translocation of CypA was suppressed in AIF-deficient harlequin mice. Immunoprecipitation of AIF revealed coprecipitation of CypA, but only in injured, ischemic tissue. Surface plasmon resonance revealed direct molecular interactions between recombinant AIF and CypA. These data indicate that the lethal translocation of AIF to the nucleus requires interaction with CypA, suggesting a model in which two proteins that normally reside in separate cytoplasmic compartments acquire novel properties when moving together to the nucleus.


Multivariate hypergeometric similarity measure.
We propose a similarity measure based on the multivariate hypergeometric distribution for the pairwise comparison of images and data vectors. The formulation and performance of the proposed measure are compared with other similarity measures using synthetic data. A method of piecewise approximation is also implemented to facilitate application of the proposed measure to large samples. Example applications of the proposed similarity measure are presented using mass spectrometry imaging data and gene expression microarray data. Results from synthetic and biological data indicate that the proposed measure is capable of providing meaningful discrimination between samples, and that it can be a useful tool for identifying potentially related samples in large-scale biological data sets.


The implication of vitamin D and autoimmunity: a comprehensive review.
Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.


House Calls: California Program For Homebound Patients Reduces Monthly Spending, Delivers Meaningful Care.
In 2009 HealthCare Partners Affiliates Medical Group, based in Southern California, launched House Calls, an in-home program that provides, coordinates, and manages care primarily for recently discharged high-risk, frail, and psychosocially compromised patients. Its purpose is to reduce preventable emergency department visits and hospital readmissions. We present data over time from this well-established program to provide an example for other new programs that are being established across the United States to serve this population with complex needs. The findings show that the initial House Calls structure, staffing patterns, and processes differed across the geographic areas that it served, and that they also evolved over time in different ways. In the same time period, all areas experienced a reduction in operating costs per patient and showed substantial reductions in monthly per patient health care spending and hospital utilization after enrollment in the House Calls program, compared to the period before enrollment. Despite more than five years of experience, the program structure continues to evolve and adjust staffing and other features to accommodate the dynamic nature of this complex patient population.


Purple nonsulfur bacteria diversity in activated sludge and its potential phosphorus-accumulating ability under different cultivation conditions.
This study investigates the diversity and the potential phosphorus-accumulating ability among the purple nonsulfur (PNS) bacteria. Traditional methods and molecular biotechniques were applied. Microscopic visualization using 4',6-diamidino-2-phenylindole staining as well as chemical analysis demonstrated that most of the isolated PNS bacteria presented different levels of phosphorus accumulation. Four of the pure cultures, denoted as Rhodopseudomonas palustris CC1, CC7, G11, and GE1, based on their differences in the PNS's pufM gene, exhibited higher internal phosphorus content compared to other isolated strains in this study. In addition, substantial polyphosphate accumulation was observed after the bacteria entered their stationary growth phase. Among them, the isolated R. palustris G11 could accumulate internal phosphorus up to 13%-15% of its cell dry weight under anaerobic illuminated incubation conditions. When the incubation status was switched from anaerobic to aerobic, the bacterial phosphorus content had a tendency to decrease slightly or remain about the same throughout the whole aerobic stage. The growth rate and biomass were higher when the PNS bacteria grew under photoheterotrophic conditions rather than the chemoheterotrophic ones. Furthermore, the environmental pH value could affect the contents of internal bacterial phosphate. Results of this study demonstrated that PNS bacteria are a group of the polyphosphate-accumulating organisms, of which this ability had never been properly studied. The conditions that PNS bacteria accumulating polyphosphate presented from this study were unique and showed characteristics that were different from the well-known enhanced biological phosphorus removal model.


Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms.
Kidney stones are one of the oldest known and common diseases in the urinary tract system. Various human studies have suggested that diets with a higher intake of vegetables and fruits play a role in the prevention of kidney stones. In this review, we have provided an overview of these dietary plants, their main chemical constituents, and their possible mechanisms of action. Camellia sinensis (green tea), Rubus idaeus (raspberry), Rubia cordifolia (common madder), Petroselinum crispum (parsley), Punica granatum (pomegranate), Pistacia lentiscus (mastic), Solanum xanthocarpum (yellow-fruit nightshade), Urtica dioica (stinging nettle), Dolichos biflorus (horse gram), Ammi visnaga (khella), Nigella sativa (black-cumin), Hibiscus sabdariffa (roselle), and Origanum vulgare (oregano) have received considerable interest based on scientific evidence. Beside these dietary plants, phytochemicals-such as catechin, epicatechin, epigallocatechin-3-gallate, diosmin, rutin, quercetin, hyperoside, and curcumin-as antioxidant dietary phyto-phenols were found to be effective for the prevention of urolithiasis (the process of stone formation in the urinary tract). The main underlying mechanisms of these dietary plants and their isolated phytonutrients in the management of urolithiasis include diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The results as presented in this review demonstrate the promising role of dietary plants and phytophenols in the prevention and management of kidney stones. Further investigations are required to confirm the safety and efficacy of these compounds.


Diagnostic markers of infection: comparison of procalcitonin with C reactive protein and leucocyte count.
Procalcitonin has been advocated as a marker of bacterial infection. To evaluate diagnostic markers of infection in critically ill children, comparing procalcitonin with C reactive protein and leucocyte count in a paediatric intensive care unit (PICU). Procalcitonin, C reactive protein, and leucocyte count were measured in 175 children, median age 16 months, on admission to the PICU. Patients were classified as: non-infected controls (43); viral infection (14); localised bacterial infection without shock (25); bacterial meningitis/encephalitis (10); or septic shock (77). Six children with "presumed septic shock" (without sufficient evidence of infection) were analysed separately. Optimum sensitivity, specificity, predictive values, and area under the receiver operating characteristic (ROC) curve were evaluated. Admission procalcitonin was significantly higher in children with septic shock (median 94.6; range 3.3-759.8 ng/ml), compared with localised bacterial infection (2.9; 0-24.3 ng/ml), viral infection (0.8; 0-4.4 ng/ml), and non-infected controls (0; 0-4.9 ng/ml). Children with bacterial meningitis had a median procalcitonin of 25.5 (7.2-118.4 ng/ml). Area under the ROC curve was 0.96 for procalcitonin, 0.83 for C reactive protein, and 0.51 for leucocyte count. Cut off concentrations for optimum prediction of septic shock were: procalcitonin > 20 ng/ml and C reactive protein > 50 mg/litre. A procalcitonin concentration > 2 ng/ml identified all patients with bacterial meningitis or septic shock. In critically ill children the admission procalcitonin concentration is a better diagnostic marker of infection than C reactive protein or leucocyte count. A procalcitonin concentration of 2 ng/ml might be useful in differentiating severe bacterial disease in infants and children.


[Mechanisms of compensation of disorders of acid-base status of the blood in patients with chronic anemia].
Altogether 228 patients with hereditary microspherocytic anemia (HMA), autoimmune hemolytic anemia (AIHA) and hypoplastic anemia (HA) were examined over time for the acid-base state of the arterial blood with the use of the pCO2-buffer bases coordinate system (BE/pCO2 and pCO2/BE diagrams). Prior to surgery the respiratory alkalosis was diagnosed in 60% of HMA patients (of these, 41.7% of patients had a decompensated alkalosis), in 61.7% of AIHA patients (73%), and in 69.7% of HA patients (82.1%). It is shown that the development in the patients of chronic respiratory alkalosis should be regarded as a compensatory mechanisms associated with hemic hypoxia complicated by arterial hypoxemia. During splenectomy, there was an increase in the incidence of decompensated respiratory alkalosis. Mixed respiratory and metabolic alkalosis occurred in 8.3% of AIHA patients and in 19.6% of HA patients because of artificial ventilation of the lungs. Two hours after operation compensated metabolic acytosis was identified in 72% of HMA patients, in 33.3% of AIHA patients, and in 33.9% of HA patients. Twenty-four hours following operation the patients of all the groups had arterial hypoxemia and hypocapnia. In view of this fact the blood acid-base state was determined by the presence of respiratory alkalosis: in 47.5% of patients with HMA, in 60% of patients with AIHA, and in 54% of patients with HA. Analysis of the BE/pCO2 diagram demonstrated that in 2/3 of the patients with HMA and AIHA and in all the patients with HA, respiratory alkalosis was decompensated. It was established that electrolyte imbalance detected in the patients interfered with metabolic compensation for chronic respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Profile and Motivations of Registered Whole-Body Donors in Turkey: Istanbul University Experience.
Little is known regarding the profiles of whole body donors in Muslim majority countries where donation is scarce. Therefore, this study aims to profile registered donors in Turkey by means of a survey. The explored data could be used to improve ongoing campaign efforts and ethical practices such as commemoration services. Registered donors of the donation programs at the two faculties of medicine of Istanbul University were compared with the national population and a cluster analysis was performed to reveal any concealed sub-groups. Data from 188 respondents were analyzed. The majority of registered donors were married (42%), male (65.4%), aged over 50 years (76%), held a tertiary education degree (49.7%), and were irreligious (58.5%). Cluster analysis revealed two groups with significantly different educational levels, marital statuses, and religious choices. Regarding whether their bodies could be used for education or research, the majority (64.5%) of the respondents left the decision to the anatomy department. Similarly, 73.8% approved indefinite use of their organs, body parts and/or skeletons. The respondents were also willing to share their medical history (94.2%) and personal information (81.6%) if needed. Motivational themes for body donation including usefulness, impermanence, religion, awareness, and kinship were devised after a thematic analysis. Among the respondents, 56.5% were registered organ donors and 63.3% were frequent blood donors. The results of this study provide data that may help revising informed consent forms, developing and implementing thanksgiving ceremonies, and selecting additional targets for supporting body donation campaign activities such as organ and blood donation units.


Epidemiology of poliomyelitis in a slum of Bombay.
A disease prevalence and immunization coverage survey in a typical slum in Bombay in the year 1988 revealed 93 children with residual poliomyelitis amongst 14,439 children below 9 years of age, indicating high (33.0/100,000 population) annual incidence of poliomyelitis. Only 62 (66.6%) of these 93 lame children sought admission in hospital during the acute phase of illness. The high incidence was attributed to a low immunization (OPV) coverage level in the most vulnerable age group. The immunization coverage for 3 doses of oral polio vaccine below 2 years of age was 43.5%. A large number of children were not commencing their immunization schedule at the right age. The survey indicated a poor "community participation" in the immunization programmes due to a poor "health awareness".


Role of phospholipase A2 isozymes in agonist-mediated signaling in proximal tubular epithelium.
Angiotensin II in proximal tubule epithelium is known to stimulate the release of arachidonic acid after stimulation of phospholipase A2 (PLA2) independent of phospholipase C-mediated signaling. Furthermore, an angiotensin II type 2 receptor subtype has been linked to this signaling cascade. We investigated the regulation and differential stimulation of PLA2s by comparing the PLA2 activities associated with the membranes and cytosol of rabbit renal proximal tubular epithelial cells after stimulation with angiotensin II, epidermal growth factor, and bradykinin. Both fractions demonstrated PLA2 activity that was dithiothreitol insensitive, required micromolar concentrations of Ca2+ for optimal activity, and was inhibited in a dose-dependent manner by an antiserum to a cytosolic PLA2 with a molecular mass of 85 kD. However, membrane-associated PLA2 did not demonstrate significant substrate specificity, whereas 1-steroyl-2-[14C]arachidonylphosphatidyl choline was the preferred substrate for cPLA2. An antiserum generated against mastoparan, a known PLA2 activator, inhibited membrane- but not cytosol-associated PLA2 activity. Membrane fractions showed a broad pH range (7.5 to 8.5) for optimal PLA2 activity, whereas cytosol was maximum at pH 9.5. Angiotensin II stimulated membrane-associated PLA2 activity by 88%, whereas bradykinin and epidermal growth factor inhibited activity by 54% and 41%, respectively. The three agonists stimulated cPLA2. Moreover, angiotensin II-induced activation of membrane-associated PLA2 preceded the activation of cPLA2. These results demonstrate differential localization and regulation of proximal tubular epithelial PLA2 isozymes, which may determine the pattern of subsequent arachidonic acid metabolism by the cytochrome P450 system.


Four basic characteristics of the gastrin-cholecystokinin system.
The gastrointestinal peptide hormones, gastrin and cholecystokinin (CCK), display four molecular characteristics. 1) Homology. Sequences of the primary structures are identical. Because the identity comprises the active site, the homology is functionally important. The homology reflects evolution from a common ancestor. 2) Heterogeneity. Each hormone exists in different molecular forms in any single species. The heterogeneity comprises both variations in lengths of the polypeptide backbone, "macroheterogeneity," and derivatizations of single amino acid residues, "microheterogeneity." Both types of modification govern the biological potency. The heterogeneity reflects enzymatic modifications of the primary ribosomal translation product. 3) Ubiquity. Each hormone is synthetized in different cell types, which are localized in gastrointestinal as well as extra-gastrointestinal tissues. The cell type determines the route by which the active peptide(s) reaches its target, either via blood (endocrine secretion) or by local release (neurocrine and paracrine secretion). Inasmuch as all cells contain gastrin and CCK genes, the variable expression probably reflects differentiation in development of the posttranscriptional biosynthetic machinery. 4) Differential principality. In different tissues and cells, different molecular forms may predominate. Moreover, one form is more potent with respect to one effect (e.g., CCK-8 in relation to pancreatic exocrine secretion), whereas another form (CCK-4) is more potent with respect to another effect (pancreatic endocrine secretion). Together the differential principality and secretory routes (blood borne or local) ensure that gastrin and CCK peptides regulate their targets with optimal effect in spite of the heterogeneity and wide distribution, which otherwise might cause disturbing interactions and subsequent inefficacy. The key to a better understanding of the basis characteristics is knowledge about the evolution and expression of the structural gene(s) for gastrin and CCK. Acquisition of such knowledge will be of considerable value, since available evidence suggests that the gastrin-CCK system is a good model for general features of regulatory peptides.


Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.
We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.


Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.
Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive. Tissue healing is a multistage regenerative process involving complex and well-orchestrated steps, which are initiated in response to injury. At best, these steps lead to scar-free tissue formation. At the onset of healing, during the inflammatory phase, stationary and attracted macrophages and other immune cells at the fracture site release cytokines in response to injury. This initial reaction to injury is followed by the recruitment, proliferation, and differentiation of mesenchymal stromal cells, synthesis of extracellular matrix proteins, angiogenesis, and finally tissue remodeling. Failure to heal is often associated with poor revascularization. Since blood vessels mediate the transport of circulating cells, oxygen, nutrients, and waste products, they appear essential for successful healing. The strategy of endogenous regeneration in a tissue such as bone is interesting to analyze since it may represent a blueprint of successful tissue formation. This review highlights the interdependency of the time cascades of inflammation, angiogenesis, and tissue regeneration. A better understanding of these inter-relations is mandatory to early identify patients at risk as well as to overcome critical clinical conditions that limit healing. Instead of purely tolerating the inflammatory phase, modulations of inflammation (immunomodulation) might represent a valid therapeutic strategy to enhance angiogenesis and foster later phases of tissue regeneration.


Patient-reported Effects of Fedratinib, an Oral, Selective Inhibitor of Janus Kinase 2, on Myelofibrosis-related Symptoms and Health-related Quality of Life in the Randomized, Placebo-controlled, Phase III JAKARTA Trial.
Patients with myelofibrosis (MF) experience an array of symptoms that impair health-related quality of life (HRQoL). Fedratinib, an oral, selective Janus-kinase 2 (JAK2) inhibitor, was investigated in the randomized, placebo-controlled, phase III JAKARTA study in adult patients with intermediate- or high-risk JAK-inhibitor-naïve MF. The effect of fedratinib 400 mg/d on patient-reported MF symptoms and HRQoL in JAKARTA was assessed. Participants completed the modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0), which evaluates 6 key MF symptoms (night sweats, early satiety, pruritus, pain under ribs on the left side, abdominal discomfort, bone/muscle pain). The modified MFSAF v2.0 was completed during the first 6 treatment cycles and at end of cycle 6 (EOC6). Symptom response was a ≥50% improvement from baseline in total symptom score (TSS). Overall HRQoL was assessed by EQ-5D-3L health utility index (HUI) score. The MFSAF-evaluable population comprised 91/96 patients randomized to fedratinib 400 mg and 85/96 patients randomized to placebo. Mean baseline TSS was 17.6 and 14.7 for fedratinib and placebo, respectively, and mean EQ-5D-3L HUI was 0.70 and 0.72. Fedratinib elicited statistically significant and clinically meaningful improvements in TSS from baseline versus placebo at all postbaseline visits. Symptom response rates at EOC6 were 40.4% with fedratinib and 8.6% with placebo (OR 7.0 [95% CI, 2.9-16.9]; P < 0.001), and a significantly higher proportion of fedratinib-treated patients achieved clinically meaningful improvement from baseline on the EQ-5D-3L HUI at EOC6 (23.2% versus 6.5%; P = 0.002). Fedratinib provided clinically meaningful improvements in MF symptoms and overall HRQoL versus placebo in patients with JAK-inhibitor-naïve MF.


Chromosome rearrangements that involve the nucleolus organizer region in Neurospora.
In approximately 3% of Neurospora crassa rearrangements, part of a chromosome arm becomes attached to the nucleolus organizer region (NOR) at one end of chromosome 2 (linkage group V). Investigations with one inversion and nine translocations of this type are reported here. They appear genetically to be nonreciprocal and terminal. When a rearrangement is heterozygous, about one-third of viable progeny are segmental aneuploids with the translocated segment present in two copies, one in normal position and one associated with the NOR. Duplications from many of the rearrangements are highly unstable, breaking down by loss of the NOR-attached segment to restore normal chromosome sequence. When most of the rearrangements are homozygous, attenuated strands can be seen extending through the unstained nucleolus at pachytene, joining the translocated distal segment to the remainder of chromosome 2. Although the rearrangements appear genetically to be nonreciprocal, molecular evidence shows that at least several of them are physically reciprocal, with a block of rDNA repeats translocated away from the NOR. Evidence that NOR-associated breakpoints are nonterminal is also provided by intercrosses between pairs of translocations that transfer different-length segments of the same donor-chromosome arm to the NOR.


Percutaneous cryoablation of 40 solid renal tumors with US guidance and CT monitoring: initial experience.
To retrospectively determine the safety and effectiveness of percutaneous cryoablation, monitored with computed tomography (CT), for the treatment of solid renal masses. This study was compliant with the Health Insurance Portability and Accountability Act and had institutional review board approval; informed consent was waived. From March 12, 2003, through August 4, 2005, 23 men and 17 women (mean age, 76 years +/- 9.7 [standard deviation]; range, 53-92 years), each with a single renal tumor, underwent one percutaneous cryoablation treatment session that combined ultrasonographic (US) guidance and CT monitoring. Technical success was defined as extension of the visible ice ball 5 mm beyond the tumor margin. Local tumor progression was defined as any tumor with intralesional enhancement or a serial increase in tumor size when compared with that on images obtained immediately after ablation. Tumor characteristics, complications, and follow-up were evaluated. The maximum diameter of the 40 treated lesions ranged from 1.5 to 7.2 cm (mean, 3.4 cm +/- 1.3). Twenty (50%) of 40 tumors were 3 cm or larger in diameter. Nineteen tumors (48%) extended into the renal sinus fat. One complication (2%) conformed to a grade 3 event, as determined with the Common Terminology Criteria for Adverse Events (version 3.0) of the National Cancer Institute; the overall complication rate was 8%. Thirty-eight (95%) of 40 cryoablation procedures were technically successful. Twenty-nine patients underwent follow-up (mean, 8.0 months +/- 4.3; range, 1.2-18.4 months); no local tumor recurrence was found. Percutaneous cryoablation with US guidance and CT monitoring is safe and effective for the treatment of solid renal tumors. Longer follow-up should provide further proof of the effectiveness of this technique.


Rescue of Recombinant Newcastle Disease Virus Expressing Heterologous Genes.
Reverse genetics allows for the generation of recombinant infectious viruses from viral sequences or complete viral genomes cloned into plasmids. Using reverse genetics, it is then possible to introduce changes in the genome of infectious viruses for multiple applications.Newcastle disease virus (NDV) is a non-segmented, negative-sense RNA virus that has been amenable to manipulation by reverse genetics for more than two decades. Since then, recombinant NDVs have been extensively used as viral vectors to express heterologous proteins. We describe the key steps required to design and introduce an additional transcription unit in the genome of the Newcastle disease virus for the efficient expression of a heterologous gene.


[Rest angina caused by coronary spasm].
A 70-year-old woman with recurrent angina at rest and dyspnea was admitted for coronary angiography. Prior to the admission an ECG showed new negative T-waves in the precordial leads, which have completely disappeared the day after. Clinical examination revealed a low systolic murmur over the aortic valve and a low murmur over the left groin artery. The other examination findings were normal. Exercise ECG revealed no signs of ischemia. In the coronary angiography a plaque in the left circumflex artery without significant lumen reduction could be detected. Intracoronary administration of acetylcholine induced a spasm in the left circumflex artery with total lumen occlusion with reproduction of intense chest pain. After injection of nitroglycerin coronary spasm and chest pain were reversible After the diagnosis of vasospastic angina pectoris medical treatment with isosorbide dinitrate and amlodipine was initiated. Additionally ACE- and CSE-inhibitors were prescribed to improve endothelial dysfunction. After one year the patient was free of symptoms. Coronary spasm can cause angina at rest. After confirmation of diagnosis an appropriate medical therapy could be applied and other unnecessary examinations including further coronary angiographies could be prevented.


A computational approach to the functional clustering of periodic gene-expression profiles.
DNA microarray analysis has emerged as a leading technology to enhance our understanding of gene regulation and function in cellular mechanism controls on a genomic scale. This technology has advanced to unravel the genetic machinery of biological rhythms by collecting massive gene-expression data in a time course. Here, we present a statistical model for clustering periodic patterns of gene expression in terms of different transcriptional profiles. The model incorporates biologically meaningful Fourier series approximations of gene periodic expression into a mixture-model-based likelihood function, thus producing results that are likely to be closer to biological relevance, as compared to those from existing models. Also because the structures of the time-dependent means and covariance matrix are modeled, the new approach displays increased statistical power and precision of parameter estimation. The approach was used to reanalyze a real example with 800 periodically expressed transcriptional genes in yeast, leading to the identification of 13 distinct patterns of gene-expression cycles. The model proposed can be useful for characterizing the complex biological effects of gene expression and generate testable hypotheses about the workings of developmental systems in a more precise quantitative way.


Upper and lower visual field differences in perceptual asymmetries.
A leftward spatial bias has been observed with visuospatial attention tasks, including line bisection and the greyscales task. Upper and lower visual field differences have been observed on various tasks, with a lower visual field advantage occurring for motion, global processing and coordinate spatial judgments. Upper visual field advantages occur for visual search, local processing and categorical judgments. In perceptual asymmetries research, upper and lower visual field differences have not typically been scored separately, as most presentations have been central. Mixed results have made it difficult to determine whether lateral biases are stronger in the upper or the lower visual field. As length of presentation time differed in prior studies, this factor was examined to determine whether it would lead differential biases to emerge in each visual field. The greyscales task was used to investigate the interaction of visual field and presentation time within subjects (N=43). Eye tracking was used during the task and supported the hypothesis of a stronger left bias in the lower visual field. Presentation time and visual field interacted to influence performance. Prolonged presentation led to a stronger leftward bias in the lower visual field whereas the leftward bias was stronger in the upper visual field during brief presentation. Results showed a relation between the lower and left visual fields and the upper and right visual fields, which has not previously been shown in perceptual asymmetries. Further, it is suggested that functional differences between the visual streams could underlie the visual field differences in perceptual asymmetries.


[Use of cycloferon in the treatment of patients with pulmonary tuberculosis with mild clinical manifestations].
to evaluate the efficacy of cyclopheron used in patients with mild clinical manifestations of focal and infiltrative pulmonary tuberculosis (PT). Thirty first detected patients with PT, in whom a complex of their etiotropic therapy comprised cyclopheron, and 32 similar patients who received etiotropic agents and placebo were examined. Tuberculosis process activity was confirmed by clinical, X-ray, bacteriological, and immunological studies. The hypothalamic-pituitary-adrenal system was determined from serum cortisol concentration. The sympathoadrenal system was assessed from cardiac rhythm parameters (autonomic balance index). Incorporation of cyclopheron into the combined therapy of patients with PT led to increased blood cortisol concentration, higher autonomic balance index, elevated T-lymphocyte count, enhanced phagocytic activity, and lower levels of circulating immune complexes, resulting in earlier decay cavity closure and sputum negativation. Extrastress status of adaptation systems and the absence of their activating impact on immunity and inflammation are detectable in first detected patients with mild clinical manifestations of PT running in significant lung tissue fibrosis. Therapy with cyclopheron that stimulates the production of stress-induced cytokines gives rise to a stress reaction, activates immune processes, and enhances therapeutic effectiveness in this group of patients.


Characterization of dengue virus resistance to brequinar in cell culture.
Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release.


Functional imaging of cerebral arteriovenous malformations with a comment on cortical reorganization.
Functional brain imaging is poised to become a standard diagnostic tool. The authors review their experience using functional positron emission tomography (fPET) in patients with cerebral arteriovenous malformations (AVMs). Twelve patients, three males and nine females aged 16 to 30 years, 11 with a cerebral AVM and one with a cavernous angioma, of which five were located in the central area and seven in a speech region, underwent fPET and three-dimensional magnetic resonance imaging. These studies were coregistered in stereotactic space and correlated to Brodmann's areas that were identified from the atlas of Talairach and Tournoux. Vibrotactile and/or motor stimulation of the contralateral hand were used to identify the central region in patients whose AVM resided within, or close to, the motor strip, and language tasks specifically designed to activate visual, auditory, expressive, or semantic language were used in patients whose AVM resided within, or close to, Broca's or Wernicke's areas. Somatosensory and motor activation reliably identified the central region in all cases as validated by identification of Brodmann's areas and by intraoperative cortical mapping, which was performed with the patient under local anesthesia. Similarly, language tasks accurately lateralized major language function to one hemisphere concordantly with neuropsychological assessment, including dichotic listening and intracarotid Amytal tests, and localized language areas appropriately as verified by stereotactic coordinates. Functional cerebral imaging is feasible in patients with structural brain lesions. It is a reliable method to identify the relationship of a cerebral AVM to the central region. The determination of a similar relationship to language areas is dependent on the development and further validation of language-based tasks designed to activate visual, auditory, expressive, and semantic aspects of language specific to particular sites within the anterior and posterior speech regions.


Impact of solvent conditions on separation and detection of basic drugs by micro liquid chromatography-mass spectrometry under overloading conditions.
In this study the impact of solvent conditions on the performance of μLC/MS for the analysis of basic drugs was investigated. Our aim was to find experimental conditions that enable high-performance chromatographic separation particularly at overloading conditions paired with a minimal loss of mass spectrometric detection sensitivity. A focus was put on the evaluation of the usability of different kinds of acidic modifiers (acetic acid (HOAc), formic acid (FA), methansulfonic acid (CH₃SO₃H), trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), and heptafluorobutyric acid (HFBA)). The test mixture consisted of eleven compounds (bunitrolol, caffeine, cocaine, codeine, diazepam, doxepin, haloperidol, 3,4-methylendioxyamphetamine, morphine, nicotine, and zolpidem). Best chromatographic performance was obtained with the perfluorinated acids. Particularly, 0.010-0.050% HFBA (v/v) was found to represent a good compromise in terms of chromatographic performance and mass spectrometric detection sensitivity. Compared to HOAc, on average a 50% reduction of the peak widths was observed. The use of HFBA was particularly advantageous for polar compounds such as nicotine; only with such a hydrophobic ion-pairing reagent chromatographic retention of nicotine was observed. Best mass spectrometric performance was obtained with HOAc and FA. Loss of detection sensitivity induced by HFBA, however, was moderate and ranged from 0 to 40%, which clearly demonstrates that improved chromatographic performance is able to compensate to a large extent the negative effect of reduced ionization efficiency on detection sensitivity. Applications of μLC/MS for the qualitative and quantitative analysis of clinical and forensic toxicological samples are presented.


Role of visually impaired in screening of diseases and the way forward.
The role of visually impaired individuals in disease screening can be significant and beneficial. While visually impaired people may have limitations related to their sight, they can still contribute to and participate in various aspects of disease screening owing to their heightened senses, especially touch. It is important to recognize that each visually impaired individual's capabilities and preferences may vary, and their involvement in disease screening should always be voluntary and based on their comfort level. However, by creating an inclusive environment and addressing accessibility barriers, visually impaired individuals may be specially empowered to engage in disease screening, particularly of the breast.


Determination of the object surface function by structured light: application to the study of spinal deformities.
The projection of structured light is a technique frequently used to determine the surface shape of an object. In this paper, a new procedure is described that efficiently resolves the correspondence between the knots of the projected grid and those obtained on the object when the projection is made. The method is based on the use of three images of the projected grid. In two of them the grid is projected over a flat surface placed, respectively, before and behind the object; both images are used for calibration. In the third image the grid is projected over the object. It is not reliant on accurate determination of the camera and projector pair relative to the grid and object. Once the method is calibrated, we can obtain the surface function by just analysing the projected grid on the object. The procedure is especially suitable for the study of objects without discontinuities or large depth gradients. It can be employed for determining, in a non-invasive way, the patient's back surface function. Symmetry differences permit a quantitative diagnosis of spinal deformities such as scoliosis.


Oro-Facial-Digital Syndrome: Unspecified Type with the Spontaneous Fusion of Cleft Palate.
Oro-facial-digital syndrome (OFD) is a disorder with varied inheritance patterns. They deal mainly with abnormalities of the face, digits, i.e., fingers and toes, and oral cavity. Hypoplasia of nasal alar cartilage, broad nasal bridge, frontal bossing, and micrognathia are the common facial abnormalities observed in its multiple potential forms. Among the oral features, lobulated tongue, multiple frenulae, and cleft lip/palate are the common findings. The subject presented in our case manifested cleft of the hard palate at the time of presentation, along with other diverse features, which could not match any of the defined OFD types in literature. Furthermore, follow-up of the infant observed closure of the palate spontaneously, without any intervention. Hence, the purpose is to add to the knowledge the typical features of this unspecified type of OFD, along with this unique unprompted cleft palate closure, which aroused the need of close watch in such cases.


Improved variational Bayes inference for transcript expression estimation.
RNA-seq studies allow for the quantification of transcript expression by aligning millions of short reads to a reference genome. However, transcripts share much of their sequence, so that many reads map to more than one place and their origin remains uncertain. This problem can be dealt using mixtures of distributions and transcript expression reduces to estimating the weights of the mixture. In this paper, variational Bayesian (VB) techniques are used in order to approximate the posterior distribution of transcript expression. VB has previously been shown to be more computationally efficient for this problem than Markov chain Monte Carlo. VB methodology can precisely estimate the posterior means, but leads to variance underestimation. For this reason, a novel approach is introduced which integrates the latent allocation variables out of the VB approximation. It is shown that this modification leads to a better marginal likelihood bound and improved estimate of the posterior variance. A set of simulation studies and application to real RNA-seq datasets highlight the improved performance of the proposed method.


Failure of large doses of ethanol to eliminate Markovian serial dependencies in neuronal spike train intervals.
The effect of drug-induced state changes on serial ordering of interaction potential intervals was evaluated by determining if the intervals were generated by a Markov process, and if they were, determining the Markov level (the degree of serial ordering) of the process before and after the injection of an intoxicating dose of ethanol. When categorizing intervals as short, medium, or long, a Markov process of level 4 (i.e., the process has a "memory" for 4 preceding adjacent intervals) was noted for most neurons; this level of serial ordering remained constant after ethanol injections. Many of the specific clusters that made the major contributions to the statistical significance before ethanol did not contribute after ethanol and a new set of clusters made the major contribution. This suggests that neurons may process intervals as "clusters" and the "cluster-length" may be a basic function of the neuron and not dependent on the general state of the organism. This methodology allows us to determine the "cluster-length" of the processor and detect and isolate the specific "clusters" that may be important state-sensitive "information carriers" (signal) in the nervous system.


Secretion in milk and transplacental transfer of two iodized oils, Lipiodol UF and Oriodol, in rabbits.
Many countries in the world are inhabited by populations suffering from iodine deficiency. These populations are affected by serious diseases directly related to iodine deficiency. Iodized oil (Lipiodol UF or Oriodol) is routinely used orally or intramuscularly to treat these populations, including pregnant women. The experiments of the present study in gravid or lactating rabbits show that there is transplacental transfer of iodine and secretion of iodine in milk after administration of iodized oil and consequently an accumulation of iodine in the thyroid glands of the mother, the fetus and the neonate. The advantages of treating pregnant women with iodized oil in the populations concerned is thus confirmed. The oral route can be substituted by the intramuscular route.


The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms.
Vfr is a global regulator of virulence factor expression in the human pathogen Pseudomonas aeruginosa. Although indirect evidence suggests that Vfr activity is controlled by cyclic AMP (cAMP), it has been hypothesized that the putative cAMP binding pocket of Vfr may accommodate additional cyclic nucleotides. In this study, we used two different approaches to generate apo-Vfr and examined its ability to bind a representative set of virulence gene promoters in the absence and presence of different allosteric effectors. Of the cyclic nucleotides tested, only cAMP was able to restore DNA binding activity to apo-Vfr. In contrast, cGMP was capable of inhibiting cAMP-Vfr DNA binding. Further, we demonstrate that vfr expression is autoregulated and cAMP dependent and involves Vfr binding to a previously unidentified site within the vfr promoter region. Using a combination of in vitro and in vivo approaches, we show that cAMP is required for Vfr-dependent regulation of a specific subset of virulence genes. In contrast, we discovered that Vfr controls expression of the lasR promoter in a cAMP-independent manner. In summary, our data support a model in which Vfr controls virulence gene expression by distinct (cAMP-dependent and -independent) mechanisms, which may allow P. aeruginosa to fine-tune its virulence program in response to specific host cues or environments.