A list-mode multi-energy window low-count SPECT reconstruction method for isotopes with multiple emission peaks.
SPECT provides a mechanism to perform absorbed-dose quantification tasks for $\alpha$-particle radiopharmaceutical therapies ($\alpha$-RPTs). However, quantitative SPECT for $\alpha$-RPT is challenging due to the low number of detected counts, the complex emission spectrum, and other image-degrading artifacts. Towards addressing these challenges, we propose a low-count quantitative SPECT reconstruction method for isotopes with multiple emission peaks. Given the low-count setting, it is important that the reconstruction method extract the maximal possible information from each detected photon. Processing data over multiple energy windows and in list-mode (LM) format provide mechanisms to achieve that objective. Towards this goal, we propose a list-mode multi-energy window (LM-MEW) OSEM-based SPECT reconstruction method that uses data from multiple energy windows in LM format, and includes the energy attribute of each detected photon. For computational efficiency, we developed a multi-GPU-based implementation of this method. The method was evaluated using 2-D SPECT simulation studies in a single-scatter setting conducted in the context of imaging [$^{223}$Ra]RaCl${_2}$. The proposed method yielded improved performance on the task of estimating activity uptake within known regions of interest in comparison to approaches that use a single energy window or use binned data. The improved performance was observed in terms of both accuracy and precision and for different sizes of the region of interest. Results of our studies show that the use of multiple energy windows and processing data in LM format with the proposed LM-MEW method led to improved quantification performance in low-count SPECT of isotopes with multiple emission peaks. These results motivate further development and validation of the LM-MEW method for such imaging applications, including for $\alpha$-RPT SPECT.


Synthesis of a versatile building block for the preparation of 6-N-derivatized α-galactosyl ceramides: rapid access to biologically active glycolipids.
A concise route to the 6-azido-6-deoxy-α-galactosyl-phytosphingosine derivative 9 is reported. Orthogonal protection of the two amino groups allows elaboration of 9 into a range of 6-N-derivatized α-galactosyl ceramides by late-stage introduction of the acyl chain of the ceramide and the 6-N-group in the sugar headgroup. Biologically active glycolipids 6 and 8 have been synthesized to illustrate the applicability of the approach.


Fiduciary responsibilities in nonprofit health care conversions.
Conversions of nonprofit hospitals to for-profit status have been controversial because of concerns that community interests are not represented in the deals. As a result, several states have either passed or are considering conversion legislation. However, dramatic variability among states in approaching conversions remains, including the extent of attorney general intervention. Federal or state legislation could standardize rules for nonprofit conversions, but such comprehensive legislation is unlikely. Instead, this article argues that CEOs and trustees of nonprofit organizations undergoing conversions must honor their fiduciary duties to ensure that a conversion represents community interests.


Daily agreeableness and acculturation processes in ethnic/racial minority freshmen: The role of inter-ethnic contact and perceived discrimination.
Having higher levels of mainstream cultural orientation (MCO), an important component of acculturation attitudes and behaviors, is beneficial for ethnic/racial minority students during the transitions into university. Scant research has investigated MCO at a micro daily timescale. This study examined how personality (agreeableness) functions in conjunction with interpersonal processes (inter-ethnic contact and perceived discrimination) to influence MCO as daily within-person processes. Multi-level structural equation modeling were used to analyze month-long daily diary data from 209 ethnic/racial minority freshmen (69% female). There was a positive indirect association between agreeableness and MCO through inter-ethnic contact at both within- and between-person levels. At the within-person level, on days with lower (vs. higher) levels of ethnic/racial discrimination, higher levels of agreeableness were associated with higher levels of MCO. These findings highlight the contributions of intensive longitudinal data in elucidating ethnic/racial minority students' personality and acculturation processes in daily life involving protective and risk factors on micro timescales.


Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum.
Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn's disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2-deficient mice inoculated with Helicobacter hepaticus, an opportunistic pathogenic bacterium, developed granulomatous inflammation of the ileum, characterized by an increased expression of Th1-related genes and inflammatory cytokines. The Peyer's patches and mesenteric lymph nodes were markedly enlarged with expansion of IFN-gamma-producing CD4 and CD8 T cells. Rip2-deficient mice exhibited a similar phenotype, suggesting that Nod2 function likely depends on the Rip2 kinase in this model. Transferring wild-type bone marrow cells into irradiated Nod2-deficient mice did not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2-deficient mice by transgenic expression of alpha-defensin in Paneth cells rescued the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts is critical for protecting mice from a Th1-driven granulomatous inflammation in the ileum. The model may provide insight into Nod2 function relevant to inflammation of ileal Crohn's disease.


Predoctoral directors: who are they and what do they do in these trying times?
Family medicine faces declining student interest and funding. Predoctoral directors will help lead efforts to overcome these challenges. Academic success will be important for predoctoral directors to be effective leaders in academic health centers. We therefore sought to describe predoctoral directors and factors associated with their academic success. We carried out a cross-sectional survey of all family medicine predoctoral directors at US allopathic medical schools using a Web-based questionnaire. The response rate was 82%. We measured academic success using a variable combining rank and tenure status. We used bivariate analysis and multiple linear regression analysis to identify factors associated with academic success. The mean age of predoctoral directors is 47, and 45% are women. Forty-two percent are assistant professors, 36% associate professors, 20% full professors, and 33% are on a tenure track. Sixty-four percent of predoctoral programs receive Title VII funding, and 63% of predoctoral directors believe that loss of Title VII funding will adversely affect student education. Factors associated with academic success include years since residency, total publications, years as predoctoral director, male gender, state funding for predoctoral family medicine programs, and participation in an academic fellowship. Involvement in educational research was associated with number of publications. Providing predoctoral directors with the skills and support needed to study their educational undertakings and publish their findings may help them achieve academic success. Medical educators must assess the effects of loss of Title VII funding on predoctoral education while seeking new sources of funding.


Size dependent targeted delivery of gold nanoparticles modified with the IL-6R-specific aptamer AIR-3A to IL-6R-carrying cells.
The delivery of gold nanoparticles (AuNPs) to specific cells strongly depends on the properties e.g. the size of the particles and is of great interest for a large variety of biomedical applications. Here we investigated the size dependence of the receptor-ligand mediated AuNP delivery to cells by comparing very small "molecular" Au-clusters of only 2 nm to larger 7 nm and 36 nm AuNPs with a distinct surface plasmon resonance. Since the molecular weight in this range changes by almost three orders of magnitude, we show how the amount of gold relates to the number of delivered AuNPs. We attached small interleukin-6 receptor (IL-6R) specific aptamer molecules (AIR-3A) in different amounts to the particles and investigated the specificity of the delivery to IL-6R-carrying cells. To reduce unspecific interaction the particles were additionally covered with polyethylene glycol (PEG). Besides particle size and concentration we varied additional parameters such as aptamer surface coverage as well as incubation time and temperature. We found that in particular, small particles with diameters of less than 2 nm show an up to six times higher delivery rate for the aptamer-conjugated AuNPs compared to untargeted PEG-coated AuNPs. The specificity reduces with a decreasing aptamer/PEG ratio, and also with an increase in particle size where the unspecific uptake is much higher. In addition we also compared the delivery efficiency of this aptamer-mediated delivery system with an antibody-mediated system targeting the same receptor to validate the performance of this approach.


Li@C60 endohedral fullerene as a supraatomic dopant for C60 electron-transporting layers promoting the efficiency of perovskite solar cells.
C60:Li@C60 hybrid n-type semiconducting films were first fabricated. The Fermi level of 1% Li@C60-added C60 films was determined to be -4.52 eV, which was 0.12 eV higher than that of pristine C60 films. A fraction of Li@C60 is distributed uniformly within the C60 film. Its application in PSCs was demonstrated, in which the addition of Li@C60 into a C60 film improved the device performance.


Structural Design Strategies for Improved Small Overlap Crashworthiness Performance.
In 2012, the Insurance Institute for Highway Safety (IIHS) began a 64 km/h small overlap frontal crash test consumer information test program. Thirteen automakers already have redesigned models to improve test performance. One or more distinct strategies are evident in these redesigns: reinforcement of the occupant compartment, use of energy-absorbing fender structures, and the addition of engagement structures to induce vehicle lateral translation. Each strategy influences vehicle kinematics, posing additional challenges for the restraint systems. The objective of this two-part study was to examine how vehicles were modified to improve small overlap test performance and then to examine how these modifications affect dummy response and restraint system performance. Among eight models tested before and after design changes, occupant compartment intrusion reductions ranged from 6 cm to 45 cm, with the highest reductions observed in models with the largest number of modifications. All redesigns included additional occupant compartment reinforcement, one-third added structures to engage the barrier, and two modified a shotgun load path. Designs with engagement structures produced greater glance-off from the barrier and exhibited lower delta Vs but experienced more lateral outboard motion of the dummy. Designs with heavy reinforcement of the occupant compartment had higher vehicle accelerations and delta V. In three cases, these apparent trade-offs were not well addressed by concurrent changes in restraint systems and resulted in increased injury risk compared with the original tests. Among the 36 models tested after design changes, the extent of design changes correlated to structural performance. Half of the vehicles with the lowest intrusion levels incorporated aspects of all three design strategies. Vehicle kinematics and dummy and restraint system characteristics were similar to those observed in the before/after pairs. Different combinations of structural improvement strategies for improving small overlap test performance were found to be effective in reducing occupant compartment intrusion and improving dummy kinematics in the IIHS small overlap test with modest weight increase.


Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.
The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches.


Concurrent chemotherapy and "concomitant boost" radiotherapy for unresectable head and neck cancer.
For patients with advanced head and neck cancer, various combined chemoradiotherapy regimens have been used to improve local control. This study was carried out to assess the outcome of concomitant chemotherapy with a "concomitant boost" radiotherapy in the treatment of advanced unresectable head and neck cancer patients. Forty-eight patients were treated with combined chemoradiotherapy between the years of 1990 and 1995. Cisplatinum (100 mg/m2) was given intravenously during week 1 and week 5. A "concomitant boost" external beam radiotherapy approach was used with twice-daily treatment delivered during the last 2 weeks. A total of 70 Gy was delivered over 6 weeks. Median follow-up was 23.5 months (2-79 months). Thirty-one (65%) and 17 (35%) patients achieved complete and partial response, respectively. Median survival in complete responders has not been reached. Overall survival at 2 years, 3 years, and 5 years were 58.7%, 52.8%, and 42.4%, respectively. Median overall survival was 38.8 months. Acute confluent mucositis (Radiation Therapy Oncology [RTOG] grade 3) developed in 50% of patients, but there was no severe long-term treatment-related toxicity. This combined chemoradiotherapy approach is safe and efficacious for advanced unresectable head and neck cancer. Treatment-related toxicity was acceptable with 50% of patients developing acute confluent mucositis. There was no severe long-term treatment-related toxicity.


Dynamical remodeling of the transcriptome during short-term anaerobiosis in Saccharomyces cerevisiae: differential response and role of Msn2 and/or Msn4 and other factors in galactose and glucose media.
In contrast to previous steady-state analyses of the O(2)-responsive transcriptome, here we examined the dynamics of the response to short-term anaerobiosis (2 generations) in both catabolite-repressed (glucose) and derepressed (galactose) cells, assessed the specific role that Msn2 and Msn4 play in mediating the response, and identified gene networks using a novel clustering approach. Upon shifting cells to anaerobic conditions in galactose medium, there was an acute ( approximately 10 min) yet transient (<45 min) induction of Msn2- and/or Msn4-regulated genes associated with the remodeling of reserve energy and catabolic pathways during the switch from mixed respiro-fermentative to strictly fermentative growth. Concomitantly, MCB- and SCB-regulated networks associated with the G(1)/S transition of the cell cycle were transiently down-regulated along with rRNA processing genes containing PAC and RRPE motifs. Remarkably, none of these gene networks were differentially expressed when cells were shifted in glucose, suggesting that a metabolically derived signal arising from the abrupt cessation of respiration, rather than O(2) deprivation per se, elicits this "stress response." By approximately 0.2 generation of anaerobiosis in both media, more chronic, heme-dependent effects were observed, including the down-regulation of Hap1-regulated networks, derepression of Rox1-regulated networks, and activation of Upc2-regulated ones. Changes in these networks result in the functional remodeling of the cell wall, sterol and sphingolipid metabolism, and dissimilatory pathways required for long-term anaerobiosis. Overall, this study reveals that the acute withdrawal of oxygen can invoke a metabolic state-dependent "stress response" but that acclimatization to oxygen deprivation is a relatively slow process involving complex changes primarily in heme-regulated gene networks.


Toward individualized cholesterol-lowering treatment in end-stage renal disease.
There is broad evidence that lowering low-density lipoprotein (LDL) cholesterol will reduce cardiovascular risk. However, in patients on maintenance hemodialysis treatment, lowering LDL cholesterol is not as effective in preventing cardiovascular complications as in the general population. Cholesterol is either endogenously synthesized or absorbed from the intestine. It has been suggested that the benefit of using statins to prevent atherosclerotic complications is less pronounced in people with high absorption of cholesterol. Recent data indicate that patients on hemodialysis have high absorption of cholesterol. Therefore, these patients may benefit from dietary counseling to reduce cholesterol intake, from functional foods containing plant sterols and stanols, and from drugs that interfere with intestinal absorption of sterols (i.e., ezetimibe, bile acid resins, and sevelamer). This review discusses cholesterol homeostasis and the perspective of personalized treatment of hypercholesterolemia in hemodialysis.


Academic medicine as a public trust.
Academic medicine is entrusted by society with the responsibility to undertake several important social missions toward improving the health of the public, including education, patient care, and research. This trust is given implicit authority by generous public funding and considerable autonomy. Medical academia can take pride in its successes, manifested by a premier scientific establishment, the development and use of sophisticated medical technologies and drugs, and the recent dramatic declines in death rates from heart disease and stroke. Academic medicine, however, has been relatively unresponsive to a number of vexing public problems, including skyrocketing expenditures for medical care, substandard indexes of population health, uneven quality of care, an unfavorable geographic and specialty mix of physicians, and widespread disability from long-term medical and psychiatric problems. Although there are many cogent reasons why academic medicine has chosen to define its task relatively narrowly (the nature of its funding successes, the intractability of the social problems, and the attractiveness of the biomedical model), the central issue is how well academic medicine is fulfilling its responsibilities to the public. To the degree that academic medicine defines its central mission narrowly, it may violate its implicit social contract and jeopardize its primary source of financial support. Alternatively, in recognition of its public responsibilities, academic medicine can choose to expand its current activities to be more responsive to the health concerns of the general population.


Robotic-Assisted Versus Traditional Full-Sternotomy Coronary Artery Bypass Grafting Procedures: A Propensity-Matched Analysis of Hospital Costs.
We aim to compare hospital costs of robotic-assisted coronary artery bypass grafting (CABG) versus conventional CABG. All consecutive 1,173 patients who underwent conventional and robotic-assisted CABG between January 2018 and June 2021 were included. After propensity-matching, 267 patients in each group (robotic-assisted vs conventional) were included in the study. Patient selection for each group was decided by a treating surgeon with a heart team based on clinical factors. Syntax score was not assessed. Total costs (direct + indirect hospital costs) of patients who underwent robotic-assisted and conventional CABG were compared. Direct cost expenses included surgical operating time, hospital stay, surgical implants and supplies, catheterization laboratory, pharmacy, radiology and ultrasound imaging, blood bank, cardiology, and so on. Indirect cost expenses included general administration medical records, and so on. Using the propensity-matched groups (n = 267), we summed the total cost by year. Results for 267 propensity-matched patients (each group) evidenced that total conventional CABG costs were $9.5 million (average of $35,580/patient), whereas robotic-assisted CABG costs were $5 million ($18,726/patient). Therefore, the differences between robotic-assisted and conventional CABG costs were $4.5 million ($16,853/patient), favoring robotic-assisted over conventional CABG. Differences in direct and indirect costs were $2.2 million and $1.8 million, respectively. When the cost of the Da Vinci robot was added ($1,200,000), the total cost was $3.3 million ($12,359 × patient) lower in the robotic-assisted CABG group. Multivariate analysis showed that, mainly, the shorter hospital length of stay (7 vs 5 days) accounts for the reduced costs observed in the robotic-assisted CABG group. In conclusion, in a mature practice, robotic-assisted CABG decreases hospital length of stay, leading to reduced hospital costs compared with conventional CABG.


Neuroscience of the yogic theory of consciousness.
Yoga as a practice and philosophy of life has been followed for more than 4500 years with known evidence of yogic practices in the Indus Valley Civilization. The last few decades have seen a resurgence in the utility of yoga and meditation as a practice with growing scientific evidence behind it. Significant scientific literature has been published, illustrating the benefits of yogic practices including 'asana', 'pranayama' and 'dhyana' on mental and physical well-being. Electrophysiological and recent functional magnetic resonance imaging (fMRI) studies have found explicit neural signatures for yogic practices. In this article, we present a review of the philosophy of yoga, based on the dualistic 'Sankhya' school, as applied to consciousness summarized by Patanjali in his yoga sutras followed by a discussion on the five 'vritti' (modulations of mind), the practice of 'pratyahara', 'dharana', 'dhyana', different states of 'samadhi', and 'samapatti'. We formulate the yogic theory of consciousness (YTC), a cohesive theory that can model both external modulations and internal states of the mind. We propose that attention, sleep and mind wandering should be understood as unique modulatory states of the mind. YTC allows us to model the external states, internal states of meditation, 'samadhi' and even the disorders of consciousness. Furthermore, we list some testable neuroscientific hypotheses that could be answered using YTC and analyse the benefits, outcomes and possible limitations.


Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis.
Glucocorticoids are used to treat respiratory dysfunction associated with premature birth but have been shown to cause neurodevelopmental deficits when used therapeutically. Recently, we established that acute glucocorticoid exposure at clinically relevant doses produces neural progenitor cell apoptosis in the external granule layer of the developing mouse cerebellum and permanent decreases in the number of cerebellar neurons. As the cerebellum naturally matures and neurogenesis is no longer needed, the external granule layer decreases proliferation and permanently disappears during the second week of life. At this same time, corticosterone (the endogenous rodent glucocorticoid) release increases and a glucocorticoid-metabolizing enzyme that protects the external granule layer against glucocorticoid receptor stimulation (11β-Hydroxysteroid-Dehydrogenase-Type 2; HSD2) naturally disappears. Here we show that HSD2 inhibition and raising corticosterone to adult physiological levels both can independently increase neural progenitor cell apoptosis in the neonatal mouse. Conversely, glucocorticoid receptor antagonism decreases natural physiological apoptosis in this same progenitor cell population suggesting that endogenous glucocorticoid stimulation may regulate apoptosis in the external granule layer. We also found that glucocorticoids which HSD2 can effectively metabolize generate less external granule layer apoptosis than glucocorticoids this enzyme is ineffective at breaking down. This finding may explain why glucocorticoids that this enzyme can metabolize are clinically effective at treating respiratory dysfunction yet seem to produce no neurodevelopmental deficits. Finally, we demonstrate that both acute and chronic glucocorticoid exposures produce external granule layer apoptosis but without appropriate control groups this effect becomes masked. These results are discussed in terms of their implications for glucocorticoid therapy and neurodevelopment during the perinatal period.


Abiotic and Biotic Contributors to Support Inter-Epidemic Francisella tularensis in an Agricultural Peri-Urban Environment.
To characterize the inter-epidemic ecology of Francisella tularensis, we surveyed vertebrates and invertebrates for the abundance, spatial distribution, and status of infection at a site in northern California that had evidence of endemic type B tularemia. We collected 2910 mosquitoes, 77 biting flies, 704 ticks, 115 mammals, and 1911 aquatic invertebrates in 2013-2014. Real-time PCR on all mosquitoes, 40 biting flies, 113 aquatic invertebrates, and 650 ticks did not detect F. tularensis DNA. Indirect enzyme linked immunosorbent assay (ELISA) on 109 mammals revealed 2 (of 2, 100%) seropositive feral cats, 1 (of 24, 4.5%) seropositive black rat, and 5 (of 10, 50%) seropositive Virginia opossums. A riparian reserve, ∼1 km from the primate research center, had the highest seroprevalence in mammals and the highest capture success for invertebrate vectors whereas opossums, cats, and ground squirrels in close proximity to the primate center had high seroprevalence and abundant fleas. Well-vegetated regions with standing water appeared to be ideal habitats for biotic components of tularemia enzootic persistence. Mesocarnivores may facilitate the spread of F. tularensis, and high densities of rodents and their fleas may be a mechanism for amplification and spillover.


Can the generalizability issue of artificial intelligence be overcome? Pneumothorax detection algorithm.
The generalizability of artificial intelligence (AI) models is a major issue in the field of AI applications. Therefore, we aimed to overcome the generalizability problem of an AI model developed for a particular center for pneumothorax detection using a small dataset for external validation. Chest radiographs of patients diagnosed with pneumothorax (n = 648) and those without pneumothorax (n = 650) who visited the Ankara University Faculty of Medicine (AUFM; center 1) were obtained. A deep learning-based pneumothorax detection algorithm (PDA-Alpha) was developed using the AUFM dataset. For implementation at the Health Sciences University (HSU; center 2), PDA-Beta was developed through external validation of PDA-Alpha using 50 radiographs with pneumothorax obtained from HSU. Both PDA algorithms were assessed using the HSU test dataset (n = 200) containing 50 pneumothorax and 150 non-pneumothorax radiographs. We compared the results generated by the algorithms with those of physicians to demonstrate the reliability of the results. The areas under the curve for PDA-Alpha and PDA-Beta were 0.993 (95% confidence interval (CI): 0.985-1.000) and 0.986 (95% CI: 0.962-1.000), respectively. Both algorithms successfully detected the presence of pneumothorax on 49/50 radiographs; however, PDA-Alpha had seven false-positive predictions, whereas PDA-Beta had one. The positive predictive value increased from 0.525 to 0.886 after external validation (p = 0.041). The physicians' sensitivity and specificity for detecting pneumothorax were 0.585 and 0.988, respectively. The performance scores of the algorithms were increased with a small dataset; however, further studies are required to determine the optimal amount of external validation data to fully address the generalizability issue.


Umbilical metastatic deposit from recurrent cholangiocarcinoma: F18-FDG PET-CT findings.
A 69-year-old woman was diagnosed with stage IIIA advanced Type IV Klatskin cholangiocarcinoma, which was treated with radical choledochectomy, extended right hepatectomy and left hepaticojejunostomy. About six months after surgery, she presented with painless jaundice. A 2-18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (F18-FDG PET-CT) was performed, which detected an FDG-avid umbilical metastatic nodule. We describe the F18-FDG PET-CT features of umbilical metastatic nodule in recurrent cholangiocarcinoma. It is sometimes difficult to detect the lesions when they present with non-specific soft tissue thickening on routine CT imaging. F18-FDG PET-CT would probably render these lesions easier to detect and interpret.


Desert dust is a risk factor for the incidence of acute myocardial infarction in Western Japan.
Recently, there has been increasing concern about adverse health effects of exposure to desert dust events. However, the association between dust and the incidence of ischemic heart diseases is unknown. The aim of the present study was to elucidate whether Asian dust (AD), a windblown sand dust originating from mineral soil in China and Mongolia, is associated with the incidence of acute myocardial infarction (AMI). We investigated the data regarding hospitalization because of AMI among 3068 consecutive patients from 4 AMI centers in Fukuoka, Japan, and data for AD from April 2003 to December 2010. We applied a time-stratified case-crossover design to examine the association between AD and the incidence of AMI. Using a conditional logistic regression analysis, we estimated the odds ratios of AMI associated with AD after controlling for ambient temperature and relative humidity. The occurrence of AD events 0 to 4 days before the day of admission was significantly associated with the incidence of AMI. In particular, the occurrence of AD 4 days before admission was significantly associated with the onset of AMI. These data suggest that exposure to AD a few days before symptom onset is associated with the incidence of AMI.


Variable duration hidden Markov model and morphological segmentation for handwritten word recognition.
This paper describes a complete system for the recognition of unconstrained handwritten words using a continuous density variable duration hidden Markov model (CD-VDHMM). First, a new segmentation algorithm based on mathematical morphology is developed to translate the 2-D image into a 1-D sequence of subcharacter symbols. This sequence of symbols is modeled by the CDVDHMM. Thirty-five features are selected to represent the character symbols in the feature space. Generally, there are two information sources associated with written text; the shape information and the linguistic knowledge. While the shape information of each character symbol is modeled as a mixture Gaussian distribution, the linguistic knowledge, i.e., constraint, is modeled as a Markov chain. The variable duration state is used to take care of the segmentation ambiguity among the consecutive characters. A modified Viterbi algorithm, which provides l globally best paths, is adapted to VDHMM by incorporating the duration probabilities for the variable duration state sequence. The general string editing method is used at the postprocessing stage. The detailed experiments are carried out for two postal applications; and successful recognition results are reported.


Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis.
The non-collagenous C-terminal domain of the alpha(3) chain of collagen IV is the autoantigen in Goodpasture disease, an autoimmune disorder described only in humans. Specific N-terminal phosphorylation is a biological feature unique to the human domain when compared with other homologous domains lacking immunopathogenic potential. We have recently cloned from a HeLa-derived cDNA library a novel serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F, Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649). We show here that the pre-mRNA of GPBP is alternatively spliced in human tissues and that the most common transcript found encodes GPBPDelta26, a molecular isoform devoid of a 26-residue serine-rich motif. Recombinantly expressed GPBPDelta26 exhibits lower activity than GPBP, due at least in part to a reduced ability of GPBPDelta26 to interact and to form very active high molecular weight aggregates. In human tissues, GPBP shows a more limited expression than GPBPDelta26 but displays a remarkable preference for the small vessels and for histological structures targeted by natural autoimmune responses including alveolar and glomerular basement membranes, the two main targets in Goodpasture disease. GPBP expression is, in turn, up-regulated in the striated muscle of a Goodpasture patient and in other autoimmune conditions including cutaneous lupus erythematosus, pemphigoid, and lichen planus.


Recent contributions of molecular biology to the clinical virology of myxoviruses.
Recent advances in the clinical virology of influenza are based on non-pragmatically oriented research on the genetics and biochemistry of the influenza virus. Antigenically hybrid recombinant viruses can be tailored to provide monospecific reagents for serological studies. Basic research on viral structure and the mechanism of viral replication has directly influenced the establishment of a cell culture system suitable for the isolation of most influenza viruses. Identification of viral genotype by RNA gel electrophoresis and mapping of oligonucleotides of viral RNA has already facilitated epidemiologic investigations. The clinical virologist of the future must have an understanding of the potential limitations of these techniques for specific strain identification.


Rhesus macaque model for ovarian cancer chemoprevention.
The objective of the study reported here was to explore whether a nonhuman primate model could be developed for chemoprevention of ovarian cancer. An initial feasibility trial was done with three monkeys to determine tolerance for these drugs and for acquisition of surgical ovarian biopsy specimens. In the study, 19 female adult Macacca mulatta (rhesus macaques) were given fenretinide (4HPR) oral contraceptive (OCP), the combination of 4HPR+OCP, or no medication for three months. Laparotomy was performed before and after drug administration, and ovarian biopsy specimens were obtained to evaluate the potential for this animal as a model for ovarian cancer chemoprevention, as well as evaluating fluorescence spectroscopy and other potential biomarkers for ovarian cancer prevention studies. The monkeys tolerated the drugs, surgeries, and acquisition of multiple ovarian biopsy specimens with resultant minimal morbidity. On initial data analysis, fluorescence spectroscopy was the marker that appeared the most promising. On the basis of results of this study, this model merits further investigation. The rhesus monkey is an excellent candidate for a nonhuman primate model for ovarian cancer chemoprevention.


Use of distortion product otoacoustic emissions to assess middle ear transducers in rhesus monkeys.
Distortion product otoacoustic emissions (DPOAEs) can provide an objective and noninvasive assessment of the peripheral cochlear function. Auditory brainstem responses measured from implanted rhesus monkeys have shown that middle ear transducers, coupled directly to the incus, are capable of delivering the signals to the central auditory system. The DPOAEs were used as a noninvasive method of assessing the frequency specificity of this mechanical transduction. In two rhesus monkeys implanted with the middle ear transducers, one primary stimulating tone (f1) was presented acoustically, and the other primary tone (f2) was presented by the transducer, which converted the signal into a mechanical motion of the probe tip attached to the body of the incus. The nonlinear characteristics of the cochlea produced the distortion product responses at the expected frequencies (2f1 - f2). This demonstrates the fidelity of the middle ear implant signal transduction in vivo. The DPOAEs also indicate minimal changes in the post-implant middle ear transmission. This study demonstrates that the DPOAEs can be used to assess the function of implanted middle ear transducers objectively and noninvasively.


[Case report on the patient who showed a primary lung carcinoma accompanied with lung metastasis from renal cell carcinoma simultaneously during the clinical follow-up].
We have studied on the patient who showed a primary lung carcinoma and microscopic metastasis from renal cell carcinoma simultaneously after nephrectomy for renal cell carcinoma. A 57-year-old man who had an incidentally discovered right renal cell carcinoma at the time of the examination of different disease, and received nephrectomy. Two years and four months after nephrectomy, a solitary primary lung carcinoma was found. Therefore, he received lobectomy. Histopathological examination revealed that the lung tumour was a poorly differentiated adenocarcinoma, and peripheral lesions of the lung tumour, it was also discovered small clear-cell carcinoma simultaneously. At that time, we could not diagnose this carcinoma as a metastatic renal cell carcinoma. Nine months after lobectomy, new coin lesions were appeared in the lung. Therefore, we diagnosed a minimum clear lesion which was found nine months ago was metastatic renal cell carcinoma clinically. At present, the patient receives interferon-alpha therapy. As a result, we diagnosed primary lung carcinoma and small metastatic renal cell carcinoma simultaneously. However, the latter diagnosis could be obtained through the progression of the disease. We conclude that we must give heed to the patients with new cancerous lesions histologically when the patients treated of cancer previously.


Vaccination-induced systemic autoimmunity in farmed Atlantic salmon.
Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single i.p. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected rodents was examined. Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and approximately 50% also reacted with other unique proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.


A Study of VO2 Max and Body Fat Percentage in Female Athletes.
Aerobic capacity of athletes is an important element of success in sports achievements. It is generally considered the best indicator of cardio respiratory endurance and athletic fitness. Body fat percentage affects VO2 max and thus the cardiovascular status of the athletes. The present study was undertaken to assess the VO2 max and body fat percentage in athletes. The secondary objective of the study was to study the relationship between VO2 max and body fat percentage. Twenty five female athletes of age group 17-22years were selected for the study. VO2 max was determined by Queen's college step test and body fat percentage by skin fold calipers. The VO2 max and body fat percentage were determined in non athletes of same age group for comparison. The statistical analysis was done by Student's t-test and Pearson correlation test. The mean VO2 max in athletic group was 39.62 ± 2.80 ml/kg/min. In non-athletic group, VO2 max was 23.54 ± 3.26 ml/kg/min. The mean body fat percentage in athletes was 24.11 ± 1.83% and in non-athletes it was 29.31 ± 3.86%.The difference in VO2 max and body fat percentage was statistically significant in our study. The VO2 max and body fat percentage in both the groups showed negative correlation by Pearson test but, was not statistically significant. The present study showed a statistically significant higher VO2 max in female athletes. The study showed a negative correlation between VO2 max and body fat percentage but was not statistically significant.


Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma.
The incidence of esophageal adenocarcinoma is increasing rapidly. Gastroesophageal reflux is a strong risk factor for this disease. The increase in incidence of esophageal adenocarcinoma coincided with the introduction of medications that promote reflux by relaxing the lower esophageal sphincter (LES), such as nitroglycerin, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines. To test the possible association between use of LES-relaxing medications and risk for adenocarcinoma of the esophagus and gastric cardia. A nationwide population-based case-control study with in-person interviews. Sweden, 1995 through 1997. 189 patients with newly diagnosed esophageal adenocarcinoma, 262 with adenocarcinoma of the gastric cardia, and 167 with esophageal squamous-cell carcinoma were compared with 820 population-based controls. Estimated incidence rate ratios, calculated by using multivariate logistic regression from case-control data with adjustment for potential confounding. Past use of LES-relaxing drugs was positively associated with risk for esophageal adenocarcinoma. Among daily, long-term users (>5 years) of LES-relaxing drugs, the estimated incidence rate ratio was 3.8 (95% CI, 2.2 to 6.4) compared with persons who had never used these drugs. Drugs of all classes contributed to the increased risk, but the association was particularly strong for anticholinergics. Short-term use of other types of LES-relaxing drugs did not seem to be strongly associated with risk. The association almost disappeared after adjustment for reflux symptoms, indicating that promotion of reflux is the link between use of LES-relaxing drugs and esophageal adenocarcinoma. If 15,490 men in any age group take LES-relaxing drugs daily for 5 years, 1 additional case of adenocarcinoma would be expected (number needed to treat for harm); in men older than 60 years of age, the number needed to treat for harm is 5,570. Assuming a causal relation, about 10% of the esophageal adenocarcinomas occurring in the population may be attributable to intake of LES-relaxing drugs. Cardia adenocarcinoma and esophageal squamous-cell carcinoma were not associated with use of LES-relaxing drugs. The widespread use of LES-relaxing drugs may have contributed to the increasing incidence of esophageal adenocarcinoma.


Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor.
Previous studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM). After investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248. Atrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.


[Diagnosis and treatment of carotid cavernous fistulas].
This article provides an overview on the actual state of the interventional neuroradiological management of carotid cavernous fistulas depending on their anatomy and pathophysiology. The results are based on our experience gained during the treatment of patients with complex CCF during the last 15 years. Indications, procedures, and results of transarterial, transvenous and combined arteriovenous approaches for balloon occlusion, embolization, coiling and stenting of these lesions are discussed. Progress in this field is constant so that new technical advances are expected to improve the safety and to expand the indications for these procedures in the future.


An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks.
Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.


Penetration of somatic mammalian cells by sperm.
Penetration of somatic mammalian cells by spermatozoa occurred after simple admixture in culture. With sperm labeled in vivo, autoradiography revealed incorporation of DNA into nuclei of recipient cells, indicating release of DNA after entrance by sperm. This system provides a new approach to study the molecular biology of information transfer and of haploid gene expression.


The influence of sodium gamma-hydroxybutyrate on GABA receptors and catecholamine effect potentiation.
The effects of microiontophoretically applied gamma-hydroxybutyric acid and gamma-hydroxybutyrate (GHBA-Na) on the extracellularly registered spontaneous neuronal electrical activity of rabbit's sensorimotor and frontal cerebral cortex were studied. GHBA-Na depressed the firing of cortical neurons in a dose-dependent manner. This effect was blocked by bicuculline. It was concluded that GHBA-Na interacted with GABA receptors of the neuronal membrane. During traumatic epilepsy GHBA-Na caused excitation of cortical neurons and showed antagonistic relationships with GABA. It is supposed that during epilepsy GHBA-Na binds with GABA receptors, decreases competitively the effect of natural GABA and thus it might cause a disinhibition of neurons. GHBA-Na increased and prolongated the depression of the neurons of frontal cortex which was caused by microiontophoretical application of catecholamines: dopamine and norepinephrine. It is suggested that GHBA-Na prevents catecholamines inactivation.


Heritability of multivariate factors of the metabolic syndrome in nondiabetic Japanese americans.
A rapidly growing body of evidence demonstrates important associations between the metabolic syndrome, characterized by a cluster of risk factors or phenotypes that include dyslipidemia, central obesity, hypertension, and hyperinsulinemia, and both cardiovascular disease and type 2 diabetes. The purpose of the present study was to characterize the metabolic syndrome in a sample of 432 individuals from 68 Japanese-American families, using factor analysis of quantitative phenotypes, and to estimate the heritability of these independent factors. Using nine characteristic phenotypes that included LDL particle size and C-reactive protein (CRP), factor analysis identified three multivariate factors interpreted as lipids, body fat/insulin/glucose/CRP, and blood pressure, explaining 65% of the variance. Heritability analysis revealed significant genetic effects on all of the factors: lipids (h(2) = 0.52, P < 0.001), body fat/insulin/glucose/CRP (h(2) = 0.27, P = 0.016), and blood pressure (h(2) = 0.25, P = 0.026). This analysis shows that independent, multivariate factors of the metabolic syndrome are heritable, demonstrating genetic influences on the underlying pathophysiological mechanisms of the syndrome.


Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) protocol.
Stroke is the leading cause of acquired disability in adulthood. Ischemic stroke often results in physical, emotional, and cognitive impairment. There is no definitively proven pharmacologic technique to accelerate recovery from stroke. The short-term goal of this study is to develop donepezil hydrochloride as pharmacotherapy for enhancing stroke recovery. The Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) is a prospective, stratified 2-stage trial of donepezil for acute ischemic stroke. Suitable patients must receive treatment within 24 hours of developing symptoms. A total of 30 to 40 patients will be enrolled. TRIAL PROCEDURES: Participants will receive up to 10 mg of donepezil daily for 90 days. Patients will be assessed at less than 24 hours (pretreatment), 30 days, 60 days, 90 days, and 6 months off-drug poststroke. Assessments will include examinations of neurologic, cognitive, functional, and psychological status. The primary outcome will be excellent neurologic recovery, defined as National Institutes of Health Stroke Scale score of 0 or 1 at 90 days after stroke. Secondary outcome measures are the proportion of patients with favorable outcomes defined as follows: National Institutes of Health Stroke Scale score of 0 or 1 at 6 months; modified Rankin scale score of 0 or 1 at 90 days and 6 months; modified Rankin scale score less than 3 at 90 days and 6 months; and Mini-Mental State Examination score greater than 24 at 90 days and 6 months. Clinicaltrials.gov identifier NCT00805792.


Bronchiolitis: recent evidence on diagnosis and management.
Viral bronchiolitis is a leading cause of acute illness and hospitalization of young children. Research into the variation in treatment and outcomes for bronchiolitis across different settings has led to evidence-based clinical practice guidelines. Ongoing investigation continues to expand this body of evidence. Authors of recent surveillance studies have defined the presence of coinfections with multiple viruses in some cases of bronchiolitis. Underlying comorbidities and young age remain the most important predictors for severe bronchiolitis. Pulse oximetry plays an important role in driving use of health care resources. Evidence-based reviews have suggested a limited role for diagnostic laboratory or radiographic tests in typical cases of bronchiolitis. Several large, recent trials have revealed a lack of efficacy for routine use of either bronchodilators or corticosteroids for treatment of bronchiolitis. Preliminary evidence suggests a potential future role for a combination of these therapies and other novel treatments such as nebulized hypertonic saline.


Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML.
DNA hypermethylation of the p15INK4b tumor suppressor gene is commonly observed in acute myeloid leukemia (AML). Repressive histone modifications and their associated binding proteins have been implicated in the regulation of DNA methylation and the transcriptional repression of genes with DNA methylation. We have used high-density chromatin immunoprecipitation-on-chip to determine the histone modifications that normally regulate p15INK4b expression in AML cells and how these marks are altered in cells that have p15INK4b DNA methylation. In AML patient blasts without p15INK4b DNA methylation, a bivalent pattern of active (H3K4me3) and repressive (H3K27me3) modifications exist at the p15INK4b promoter. AML patient blasts with p15INK4b DNA methylation lose H3K4me3 at p15INK4b and become exclusively marked by H3K27me3. H3K27me3, as well as EZH2, extends throughout p14ARF and p16INK4a, indicating that polycomb repression of p15INK4b is a common feature in all AML blasts irrespective of the DNA methylation status of the gene. Reactivation of p15INK4b expression in AML cell lines and patient blasts using 5-aza-2'-deoxycytidine (decitabine) and trichostatin A increased H3K4me3 and maintained H3K27me3 enrichment at p15INK4b. These data indicate that AML cells with p15INK4b DNA methylation have an altered histone methylation pattern compared with unmethylated samples and that these changes are reversible by epigenetic drugs.


[Multi-professional epilepsy teams including psychiatric expertise].
Epilepsy has a diverse spectrum of consequences that can necessitate multi-professional cooperation in order to guarantee a high level of care. Psychiatric comorbidity is common, which influences quality of life, seizure control and mortality. Multi-professional teams, with participation from neurology, psychiatry, psychology, occupational therapy and social work, can together tailor the individual care for patients with complex needs. Close cooperation among team members increases quality and efficiency of care and reassurance for patients and their relatives while decreasing the work load for individual team members.


Epigenetics and early domestication: differences in hypothalamic DNA methylation between red junglefowl divergently selected for high or low fear of humans.
Domestication of animals leads to large phenotypic alterations within a short evolutionary time-period. Such alterations are caused by genomic variations, yet the prevalence of modified traits is higher than expected if they were caused only by classical genetics and mutations. Epigenetic mechanisms may also be important in driving domesticated phenotypes such as behavior traits. Gene expression can be modulated epigenetically by mechanisms such as DNA methylation, resulting in modifications that are not only variable and susceptible to environmental stimuli, but also sometimes transgenerationally stable. To study such mechanisms in early domestication, we used as model two selected lines of red junglefowl (ancestors of modern chickens) that were bred for either high or low fear of humans over five generations, and investigated differences in hypothalamic DNA methylation between the two populations. Twenty-two 1-kb windows were differentially methylated between the two selected lines at p < 0.05 after false discovery rate correction. The annotated functions of the genes within these windows indicated epigenetic regulation of metabolic and signaling pathways, which agrees with the changes in gene expression that were previously reported for the same tissue and animals. Our results show that selection for an important domestication-related behavioral trait such as tameness can cause divergent epigenetic patterns within only five generations, and that these changes could have an important role in chicken domestication.


Impact of pharmacological and non-pharmacological interventions on mortality in chronic obstructive pulmonary disease (COPD) patients.
This review aimed to summarise evidence about the impact of pharmacological and non-pharmacological interventions on survival in COPD patients. We performed a narrative literature review on the effect of pharmacological and non-pharmacological interventions on survival in COPD patients. Inhaled therapies are central to reduce symptoms in COPD. In particular, inhaled steroids seem to have the greatest effect on mortality. Despite the anti-inflammatory effects attributed to statins, their benefit in COPD has been shown only in cases of combined cardiovascular diseases. The use of beta-blockers in COPD has not been associated with increased COPD-related mortality and a beneficial effect on all-cause mortality has even been shown in COPD patients with cardiovascular diseases. Influenza and pneumococcal vaccination reduced the occurrence of exacerbations and mortality due to COPD. In addition, long-term oxygen therapy (LTOT) (≥15h/day) in COPD patients with severe hypoxemia had a positive effect on survival. Regarding non-pharmacological interventions, it has been demonstrated that smoking cessation, treatment compliance and nutritional supplementation for underweight patients also have a positive effect on survival. Non-invasive ventilation results were dependent on patient PaCO2 levels. In patients with advanced COPD, further prospective studies are needed to know the effect of bronchoscopic lung volume reduction and lung transplant on COPD survival. Regarding lung transplant, a survival benefit in patients with a pre-transplant BODE score of ≥7 has been shown in retrospective studies. Most of the studies did not evaluate survival as the main criteria and further long-term studies on the global management of COPD are required.


[Personalised psychiatry: no substitute for personal care].
Personalised psychiatry is the promise that biological stratification and analysis of 'big' data will enable clinical prediction.
 AIM: To analyse promises and problems regarding personalised medicine in the psychiatry.
 METHOD: Analysis of current challenges.
 RESULTS: Essential challenges are: 1. Biological psychiatry yields weak findings and clinically negligible diagnostic likelihood ratios. 2. The impact of biological stratification in medicine is relatively small yet may result in explosive health care costs. 3. Equivalent investment in public mental health may result in considerably higher health gains. 4. Data quality may be more important than data density. 5. The promise of biological stratification detracts from a hermeneutic approach and a focus on connectedness, meaning and identity.
 CONCLUSION: Personal care with a focus on the unique narrative development and the non-linear process of enhancing resilience, in combination with within-person (n=1) predictive measurements (emotional, biological or other), may represent the best way to link the practice of psychiatry with the promise of personalised medicine.


Functionally oriented analysis of cardiometabolic traits in a trans-ethnic sample.
Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (1) and determined genes with differential predicted expression by trait. PrediXcan imputes tissue-specific expression levels from genetic variation using variant-level effect on gene expression in transcriptome data. To explore the value of imputed genetically regulated gene expression (GReX) models across different ancestral populations, we evaluated imputed expression levels for predictive accuracy genome-wide in RNA sequence data in samples drawn from European-ancestry and African-ancestry populations and identified substantial predictive power using European-derived models in a non-European target population. We then tested the association of GReX on 15 cardiometabolic traits including blood lipid levels, body mass index, height, blood pressure, fasting glucose and insulin, RR interval, fibrinogen level, factor VII level and white blood cell and platelet counts in 15 755 individuals across three ancestry groups, resulting in 20 novel gene-phenotype associations reaching experiment-wide significance across ancestries. In addition, we identified 18 significant novel gene-phenotype associations in our ancestry-specific analyses. Top associations were assessed for additional support via query of S-PrediXcan (2) results derived from publicly available genome-wide association studies summary data. Collectively, these findings illustrate the utility of transcriptome-based imputation models for discovery of cardiometabolic effect genes in a diverse dataset.


A Comparison of Intervention Intensity and Service Delivery Models With School-Age Children With Speech Sound Disorders in a School Setting.
Purpose This study examined intervention intensity and service delivery with school-age children with mild or mild-moderate speech sound disorders. The commonly used business-as-usual (BAU) service delivery model and a shorter, more frequent, individual model (experimental [EXP]) were compared. Method A between-subjects group design was selected. In BAU, 11 children received group sessions, 2 times per week, 30 min per session for 6 weeks. In EXP, 11 children received individual session, 3 times per week, 5 min per session for 6 weeks. Group differences on measures of dose (i.e., therapeutic input and production trials) and cumulative treatment intensity were examined. The extent to which children, across both conditions, demonstrated gains in speech sound accuracy and the extent to which gains differed between BAU and EXP were examined. Results There was a significant group difference on dose. Children in BAU received more therapeutic input and production trials than children in EXP. Cumulative treatment intensity was not statistically different between groups when dose was calculated as therapeutic input or production trials. Results from both conditions indicated statistically significant differences on measures of speech sound accuracy with large effect sizes. No group differences on gains were noted. Conclusions Dose calculated as therapeutic input and production trials plays an important role in understanding the impact of cumulative intervention intensity. Children with mild or mild-moderate speech sound disorders may benefit more from a shorter, frequent, individual service delivery model than a BAU model.


CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.
Systemic tolerance can be elicited by introducing antigen into an immune-privileged site, such as the eye, or directly into the blood. Both routes of immunization result in a selective deficiency of systemic delayed type hypersensitivity. Although the experimental animal model of anterior chamber-associated immune deviation (ACAID) occurs in most mouse strains, ACAID cannot be induced in several mutant mouse strains that are coincidentally deficient in natural killer T (NKT) cells. Therefore, this model for immune-privileged site-mediated tolerance provided us with an excellent format for studying the role of NKT cells in the development of tolerance. The following data show that CD1-reactive NKT cells are required for the development of systemic tolerance induced via the eye as follows: (a) CD1 knockout mice were unable to develop ACAID unless they were reconstituted with NKT cells together with CD1(+) antigen-presenting cells; (b) specific antibody depletion of NKT cells in vivo abrogated the development of ACAID; and (c) anti-CD1 monoclonal antibody treatment of wild-type mice prevented ACAID development. Significantly, CD1-reactive NKT cells were not required for intravenously induced systemic tolerance, thereby establishing that different mechanisms mediate development of tolerance to antigens inoculated by these routes. A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in self-tolerance and their defects in autoimmunity.


The social determinants of mental health disorders among women with infertility: a systematic review.
Infertility is associated with mental health disorders in women, even if a successful pregnancy resolves infertility. However, the link between social determinants of health (SDoH) and mental health in women with infertility is not well understood. We aimed to investigate the determinants thoroughly so that mental health screening and services can be tailored to suit women with infertility who are vulnerable to mental health disorders. All observational studies that included women participants of reproductive age with infertility and assessed social determinants associated with mental health disorders were searched using a combination of keywords from MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, and Web of Science databases and published in English. Two reviewers conducted screening, data extraction, quality assessment and risk of bias. The protocol was registered on PROSPERO (number CRD42022343962). The systematic review included 32 studies out of 3405 screened articles from January 1st 2010 to 16th October 2023. Compared to women without infertility, the prevalence of mental health disorders, including anxiety, depression, psychological distress, and stress, is high among women with infertility, with the severity being influenced by social determinants-those with higher education, employment, higher personal or family income, private health insurance, higher social support, stronger religious beliefs, and higher spiritual well-being reported better mental health outcomes. The study highlights the need for early detection, tailored interventions, and integrated and comprehensive support systems to address the mental health needs of women with infertility and improve their well-being.


Experimental models of acute lung injury in the newborns.
Acute lung injury in the preterm newborns can originate from prematurity of the lung and insufficient synthesis of pulmonary surfactant. This situation is known as respiratory distress syndrome (RDS). In the term neonates, the respiratory insufficiency is related to a secondary inactivation of the pulmonary surfactant, for instance, by action of endotoxins in bacterial pneumonia or by effects of aspirated meconium. The use of experimental models of the mentioned situations provides new information on the pathophysiology of these disorders and offers unique possibility to test novel therapeutic approaches in the conditions which are very similar to the clinical syndromes. Herewith we review the advantages and limitations of the use of experimental models of RDS and meconium aspiration syndrome (MAS) and their value for clinics.


beta-Naphthoflavone and 3'-methoxy-4'-nitroflavone exert ambiguous effects on Ah receptor-dependent cell proliferation and gene expression in rat liver 'stem-like' cells.
Both natural and synthetic flavonoids are known to interact with the aryl hydrocarbon receptor (AhR); however, their agonist/antagonist properties in vitro have been so far studied mostly in the context of cytochrome P450 1A1 gene (Cyp1a1) regulation. We investigated effects of two synthetic flavones known either as AhR agonist (beta-naphthoflavone; BNF) or antagonist (3'-methoxy-4'-nitroflavone; 3M4NF), using an in vitro model of liver 'stem-like' cells, on expression of various AhR target genes and AhR-dependent cell proliferation. We found that the presumed antagonist 3M4NF induces a partial nuclear translocation and activation of AhR. Although inhibiting the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Cyp1a1 expression, 3M4NF alone induced a minor increase of CYP1A1 mRNA and protein. However, 3M4NF did not induce AhR binding to synthetic dioxin response elements (DRE). In contrast to Cyp1a1, 3M4NF induced a marked expression of other AhR-regulated genes, such as Cyp1b1 and Nqo1, as well as transcriptional repression of Cdh13 gene, confirming that its effects may be promoter-context specific. Like BNF, 3M4NF induced AhR-dependent cell proliferation of contact-inhibited rat liver 'stem-like' WB-F344 cells, associated with a marked upregulation of Cyclin A, as well as the downregulation of proteins involved in formation of cell-cell contacts. Based on these experimental findings, we conclude that partial agonists/antagonists of AhR can increase cell proliferation rate and AhR-dependent genes expression in both cell type- and gene-specific manner. The specificity of effects of flavones on diverse AhR targets should be taken into account, when studying AhR signaling using presumed AhR antagonists.


Pyogenic hepatic abscesses.
A review of pyogenic liver abscess at the University of Alabama in Birmingham revealed 29 cases, of which 22 were single and seven were multiple. Etiology was cryptogenic in 11, secondary to biliary tract disease in seven, trauma in six, and pyelophlebitis in four, and secondary infection in a primary neoplasm in one. No single set of specific diagnostic criteria could be elucidated, but fever occurred in every patient. Leukocytosis, hypoalbuminemia, and elevated alkaline phosphatase were present in more than 80 per cent of patients. Other clinical findings and routine laboratory abnormalities were less consistently present. In suspect patients, a technetium-99 scan was positive in 18 of 19. Ten patients died, including six of seven with multiple abscesses, seven of seven with positive abscess and blood cultures, and seven of 11 in whom liver abscess was not suspected prior to operation or autopsy. Diagnosis demands a high index of suspicion, in patients in whom suggestive factors are present, and liberal use of the technetium-99 scan. Successful treatment requires exploratory laparotomy, with care of discern any underlying septic focus or the presence of multiple abscesses, and wide drainage of the abscesses, as well as vigorous supportive care and appropriate antibiotics.


Identification of intraplaque hemorrhage on MR angiography images: a comparison of contrast-enhanced mask and time-of-flight techniques.
MRA is widely used to measure carotid narrowing. Standard CE- and TOF-MRA techniques use highly T1-weighted gradient-echo sequences that can detect T1 short blood products, so they have the potential to identify IPH, an indicator of plaque rupture. We sought to determine the accuracy and reliability of these MRA sequences to detect IPH. 3D TOF and CE carotid MRA scans were obtained at 3T on 15 patients (age range, 58-86 years; 13 men) scheduled for CEA. The source images from the precontrast (mask) CE-MRA and the TOF sequences were reviewed by 2 independent readers for IPH presence (identified as hyperintense signal intensity compared with adjacent muscle). CEA specimens were stained with antibody against glycophorin A and Mallory stain to detect IPH and were correlated with MR images. Nine of 15 CEA specimens (61 of 144 MR images) contained IPH confirmed by histology. Compared with TOF, CE-MRA mask demonstrated greater sensitivity, specificity, PPV, and NPV for IPH detection. The accuracy for correctly identifying IPH by using CE-MRA mask images and TOF images was 94% and 84%, respectively. Inter- and intraobserver agreement for IPH detection was excellent by mask images (κ = 0.91 and κ = 0.94, respectively) and TOF images (κ = 0.77 and κ = 0.84, respectively). CE-MRA mask images are highly accurate and reliable for identifying IPH, more so than the TOF sequence, and can potentially provide valuable information about risk for rupture.


Assessing the application of the Synergy Model in hematology to improve care delivery and the work environment.
A pilot project was undertaken to evaluate the impact of the Synergy Model (Curley, 1998) on patient care delivery and professional practice in a hematology unit. Patient characteristics were matched to nurse competency when making the nursing assignments and acuity scores were used to make staffing adjustments. The model resulted in "better fit" assignments, with 87% of nurses reporting their competencies were well matched with patient acuity, compared to 48% before the model implementation. Nurse satisfaction regarding the level of support for novice nurses, involvement in nursing assignments, workload, and engagement also improved. Reduction in safety occurrences and overtime were also observed. The Synergy Model offers a promising framework for improving care delivery and the practice environment in other similar patient populations.


The linker region plays an important role in the interdomain communication of the response regulator OmpR.
OmpR is the response regulator of a two-component regulatory system that controls the expression of the porin genes ompF and ompC in Escherichia coli. This regulator consists of two domains joined by a flexible linker region. The amino-terminal domain is phosphorylated by the sensor kinase EnvZ, and the carboxyl-terminal domain binds DNA via a winged helix-turn-helix motif. In vitro studies have shown that amino-terminal phosphorylation enhances the DNA binding affinity of OmpR and, conversely, that DNA binding by the carboxyl terminus increases OmpR phosphorylation. In the present work, we demonstrate that the linker region contributes to this communication between the two domains of OmpR. Changing the specific amino acid composition of the linker alters OmpR function, as does increasing or decreasing its length. Three linker mutants give rise to an OmpF(+) OmpC(-) phenotype, but the defects are not due to a shared molecular mechanism. Currently, functional homology between response regulators is predicted based on similarities in the amino and carboxyl-terminal domains. The results presented here indicate that linker length and composition should also be considered. Furthermore, classification of response regulators in the same subfamily does not necessarily imply that they share a common response mechanism.


[A factor analytic study of the items for the personality description based on the principle of the three traits theory for the work curve of addition of the Uchida-Kraepelin psychodiagnostic test].
An inventory form for the personality description based on the principle of the three traits theory for the work curve of the Uchida-Kraepelin psychodiagnostic test was investigated from the factor-analytic point of view. Three kinds of analyses were performed. First of all, the 66 items of the present form were administrated and a tentative orthogonal factor solution was obtained. Secondly, the 20 items for a simplified pattern in the sense of "simple structure" were selected based on the result of the first factor rotation, and the further orthogonal factor rotation was applied to the data based on the selected items so that the assumption for the three traits, primacy (A), variability (B), and, recency (C) were confirmed factor-analytically. Finally, in order to increase the number of items for providing an extended form for academic and practical use, more 10 items were added to the 20 items of the second analysis after applying the third orthogonal factor rotation so that the new form consisting of 30 items was obtained. Some relationships between the present work and the one of Eysenck and Eysenck (1968) were discussed.


The influence of polymorphism at position 16 of the beta2-adrenoceptor on the development of tolerance to beta-agonist.
Polymorphism at position 16 of the beta2-adrenoceptor alters receptor down-regulation in vitro. Our aim was to compare the development of tolerance to beta-agonist in homozygous Gly-16 patients with patients harboring the "wild" genotype (homozygous Arg-16) during regular treatment with salmeterol. In a prospective, randomized, double-blind, placebo-controlled, cross-over study, 20 subjects with mild to moderate asthma (10 Gly-16, 10 Arg-16) received 2 weeks of treatment with inhaled salmeterol 100 microg b.i.d. Thereafter, dose responses to inhaled salbutamol were constructed for forced expiratory volume in 1 sec (FEV1), heart rate, QTc interval, serum potassium and glucose, and finger tremor. The protective effect of salbutamol against adenosine monophosphate (AMP) challenge was also measured. Salmeterol resulted in a significant reduction in the area under curve (AUC) for FEV1 (p = 0.01), heart rate (p = 0.01), QTc interval (p = 0.01), and tremor (p = 0.05), and in the maximum responses for FEV1 (p = 0.05), heart rate (p = 0.02), and glucose (p = 0.02). The protective effect of salbutamol against AMP was reduced by 3.61 doubling doses (p < 0.001). However, differences between Gly-16 and Arg-16 patients were small and nonsignificant. Thus, although tolerance is influenced in vitro by polymorphism of the beta2-adrenoceptor, the magnitude of between-genotype differences in vivo is unlikely to be significant.


Noncoding Microdeletion in Mouse Hgf Disrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39.
Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39 However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.


Determination of phenanthrene and hydroxyphenanthrenes in various biological matrices at trace levels using gas chromatography-mass spectrometry.
A fast and efficient multiresidue extraction-purification procedure was developed for low levels (ppb range) of phenanthrene and hydroxyphenanthrene in biological matrices, in order to quantify phenanthrene and metabolites in blood, milk, urine, and biological tissues of lactating goats. Detection and identification of the analytes (phenanthrene and 1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene) were achieved using gas chromatography coupled to mass spectrometry. Deuterium-labeled phenanthrene was used as internal standard for phenanthrene and 2-OHfluorene for metabolites. The developed method includes enzymatic hydrolysis, liquid-liquid extraction, and Envi-Chrom P SPE column purification. Analyses were performed in the selected ion monitoring mode to achieve ad hoc sensitivity in accordance with analyte concentrations in food samples. Detection limits were between 2.3 and 5.1 ng/mL (ppb) for milk samples, 0.5 and 2.5 ng/mL for urine and blood samples, and 1.9 and 8.0 ng/g for tissue samples. This original multiresidue and multimatrix analytical methodology was applied to metabolism studies and polycyclic aromatic hydrocarbon (PAH) risk assessment. We demonstrated, for the first time, that metabolites were present in milk. These results suggested that usual PAHs analysis methods based on the detection of native molecule are not representative of the real contamination of biological matrices.


The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis.
Recently, there has been an increasing amount of literature published on the effects of 4-phenylbutyric acid (4-PBA) in various biological systems. 4-PBA is currently used clinically to treat urea cycle disorders under the trade name Buphenyl. Recent studies however have explored 4-PBA in the context of a low weight molecular weight chemical chaperone. Its properties as a chemical chaperone prevent misfolded protein aggregation and alleviate endoplasmic reticulum (ER) stress. As the ER is responsible for folding proteins targeted for use in membranes or secreted out of the cell, failure of maintaining adequate ER homeostasis may lead to protein misfolding and subsequent cell and organ pathology. Accumulation of misfolded proteins within the ER activates the unfolded protein response (UPR), a molecular repair response. The activation of the UPR aims to restore ER and cellular proteostasis by regulating the rate of synthesis of newly formed proteins as well as initiating molecular programs aimed to help fold or degrade misfolded proteins. If proteostasis is not restored, the UPR may initiate pro-apoptotic pathways. It is suggested that 4-PBA may help fold proteins in the ER, attenuating the activation of the UPR, and thus potentially alleviating various pathologies. This review discusses the biomedical research exploring the potential therapeutic effects of 4-PBA in various in vitro and in vivo model systems and clinical trials, while also commenting on the possible mechanisms of action.


The effect of K-252a, a potent microbial inhibitor of protein kinase, on activated cyclic nucleotide phosphodiesterase.
K-252a, an indole carbazol compound of microbial origin, inhibited activation of bovine brain phosphodiesterase induced by calmodulin (CaM), sodium oleate, or limited proteolysis with almost equal potency. Kinetic analysis revealed that the CaM-activated phosphodiesterase (CaM-PDE) was competitively inhibited by K-252a with respect to CaM. On the other hand, inhibition of the trypsin-activated phosphodiesterase was competitive with respect to cyclic AMP. Addition of a lower amount of phosphatidylserine or sodium oleate to the reaction medium was efficacious in attenuating the inhibition of the CaM-PDE by W-7, compound 48/80, or calmidazolium but, in contrast, had no effect on the inhibition by K-252a. Furthermore, CaM-independent systems such as [3H]nitrendipine receptor binding or Na+ + K+-ATPase were influenced less by K-252a compared with W-7, compound 48/80 and calmidazolium. In conclusion, K-252a is an inhibitor of CaM-dependent cyclic nucleotide phosphodiesterase and it appears that it inhibits the enzyme not only via CaM antagonism but possibly also by interfering with the enzyme.


The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study.
To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.


Suicidal ideation in adolescence: Depression, substance use, and other risk factors.
The interrelationships of depression and suicide with adolescent drug use, delinquency, eating disorders, and the risk factors for these different problems were investigated among 597 9th and 11th graders in an urban high school. There is a strong association of drug use with suicidal ideation among girls, and a stronger relationship with attempts among girls and boys. Suicidal youths are ill-adjusted and display a lack of attachment and commitment to family and school. Causal models indicate that poor interpersonal interactions with parents, absence of peer interactions, and life events lead to depression, which in turn leads to suicidal ideation. Depressive symptoms are the strongest predictors of suicidal ideation. Among females, depression predicts drug involvement, and in turn, drug use increases suicidal ideation. Drug use is only one class of problem behaviors that constitutes a risk factor for suicidal behavior in adolescence. Delinquency and eating disorders also have direct effects on suicidal ideation beyond those of depressive affect. As for drug involvement, these problem behaviors are more predictive of suicidal behavior among girls than boys. Similarity and specificity of the predictors for problem behaviors within and between the sexes are discussed. Although young women use drugs to handle feelings of depression, drug use appears ineffective in the long run in relieving these depressive feelings. Understanding the dynamics of suicidal ideation in adolescence has important public health implications, since ideation is a strong predictor of attempts, especially among females.


Effect of praziquantel on hematuria and proteinuria in urinary schistosomiasis.
In five settlements on Lake Volta, Ghana, 230 persons infected with S. haematobium were treated with either 30 or 40 mg/kg of praziquantel. Both treatment regimes gave similar overall cure rates (60%) and reduction in geometric mean egg counts (92%) at a six-month follow-up. In this highly endemic area, 32% of the initial urine specimens were visibly bloody and only 4% remained bloody after treatment. Geometric mean egg counts of visibly bloody urine specimens were two to six times higher than normal appearing urine specimens. In children under 15 years of age, gross hematuria was reduced by 91% and hematuria as detected by reagent strips was reduced by 77% after treatment with praziquantel. Among adults, gross hematuria was reduced by 76% and hematuria as detected by reagent strips was reduced by 68%. Reduction was observed in 74% of all persons with 100 mg of protein/100 ml of urine or more prior to treatment. The cure rate with praziquantel was only 36.1% in children who had visibly bloody urine specimens associated with high geometric mean egg counts prior to treatment. The lowest cure rate (15.4%) was observed in persons with persistent hematuria and proteinuria after treatment although the geometric mean urinary egg count was reduced 84%. In infected individuals without hematuria or proteinuria prior to treatment, the cure rate was 96%. This study demonstrated that praziquantel reduced clinical signs due to S. haematobium infection as well as achieved a high cure rate and/or reduction of egg excretion. Conversely, individuals with clinical signs of hematuria and proteinuria had a lower cure rate with praziquantel than individuals without clinical signs.


Smoking and weight change after new health diagnoses in older adults.
Smoking and patterns of diet and activity are the 2 leading underlying causes of death in the United States, yet the factors that prompt individuals to adopt healthier habits are not well understood. This study was undertaken to determine whether individuals who have experienced recent adverse health events are more likely to quit smoking or to lose weight than those without recent events using Health and Retirement Study panel survey data for 20 221 overweight or obese individuals younger than 75 years and 7764 smokers from 1992 to 2000. In multivariate analyses, adults with recent diagnoses of stroke, cancer, lung disease, heart disease, or diabetes mellitus were 3.2 times more likely to quit smoking than were individuals without new diagnoses (P < .001). Among overweight or obese individuals younger than 75 years, those with recent diagnoses of lung disease, heart disease, or diabetes mellitus lost -0.35 U of body mass index (calculated as weight in kilograms divided by height in meters squared) compared with those without these new diagnoses (P < .001). Smokers with multiple new diagnoses were 6 times more likely to quit smoking compared with those with no new diagnoses. The odds of quitting smoking were 5 times greater in individuals with a new diagnosis of heart disease, and body mass index declined by 0.6 U in overweight or obese individuals with a new diagnosis of diabetes mellitus (P < .001). Across a range of health conditions, new diagnoses can serve as a window of opportunity that prompts older adults to change health habits, in particular, to quit smoking. Quality improvement efforts targeting secondary as well as primary prevention through the health care system are likely well founded.


Chitinophaga tropicalis sp. nov., isolated from forest soil.
A novel bacterial strain, designated ysch24T, was isolated from a forest soil sample collected from the Cat Tien National Park, southern Vietnam. Cells were Gram-stain-negative, aerobic, gliding, filamentous or rod-shaped. The results of 16S rRNA gene analyses revealed that strain ysch24T belongs to the genus Chitinophaga, and was most closely related to Chitinophaga silvisoli GDMCC 1.1411T (97.4 %), followed by Chitinophaga oryziterrae JCM 16595T (97.3 %) and Chitinophaga sancti NBRC 15057T (96.9 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain ysch24T and closely related type strains were 72.0-74.0 % and 19.1-19.4 %, respectively. Major fatty acids were iso-C15 : 0, C16 : 1 ω5c and iso-C17 : 0 3-OH and the predominant respiratory quinone was menaquinone 7. Polar lipids consisted of phosphatidylethanolamine, four unidentified aminophospholipids, two unidentified phospholipids and four unidentified lipids. The genomic DNA G+C content was 45.6 mol%. The study clearly showed that strain ysch24T should represent a novel species of the genus Chitinophaga, for which the name Chitinophaga tropicalis sp. nov. is proposed. The type strain is ysch24T (=GDMCC 1.1355T=KACC 21527T).


Laser cyclophotocoagulation enhances the regulative capacity of retinal vessels in glaucoma.
To determine the effects of laser surgical IOP reduction by means of transscleral cyclophotocoagulation (CPC) on retinal blood flow parameters in glaucoma patients using Dynamic Vessel Analysis (DVA). 26 patients (average age: 70 years) with a long history of primary open angle glaucoma underwent CPC. The effect on the reactive capacity of retinal vessels was assessed before and 6-8 weeks after CPC by means of the Dynamic Vessel Analyzer (DVA) using flicker light provocation. In our group of POAG patients, IOP was significantly reduced about approximately 20% by CPC while systemic blood pressure and heart rate were not changed. The most obvious differences between the pre- and postoperative DVA measurements could be observed in the maximal dilation of the retinal arteries which increased from 0.75 % (+/- 0.6) to 3.17 % (+/- 0.5) with an average increase of 2.4 % (p<0.01). In addition, the ability of the arteries for constriction improved significantly (p<0.05) while the dynamic responses of the veins and the initial baseline values (MU) of the vessel diameters did not change. Our results of DVA measurements after an IOP-lowering laser surgical intervention (CPC) reveal a significant recovery of the regulative capacity of retinal arteries in glaucoma patients that has up to now neither been properly documented nor appreciated. Future studies with long-term follow-up must determine the clinical importance of these findings for the treatment of glaucoma patients.


Cellular actions of halothane on cat cerebral arterial muscle.
The effects of halothane on intracellular membrane potential (Em) and force development in cat MCA were studied. Halothane (0.07-0.14 mM/1) relaxed isolated MCA which had developed myogenic tone. Measurement of Em showed that halothane depolarized this preparation in a dose-dependent fashion in the face of vessel relaxation, demonstrating uncoupling of electrical and mechanical activity. Halothane markedly inhibited the contractile effects of histamine and serotonin suggesting that, apart from its direct action on cerebral arterial tone, it also blunts the action of vasoactive agents. When this preparation is partially depolarized from -62 to -50 mV with excess K+, halothane, while having only a small (1.2 mV) additional depolarizing effect, consistently elicits contraction rather than relaxation. Thus, the action of this particular volatile anesthetic on cerebral arteries can depend upon the resting level of Em. These studies indicate that halothane relaxes myogenic tone in cat MCA by an intracellular mechanism, but that the direction of its effect (i.e., relaxation vs. contraction) may depend upon the prior level of Em and muscle cell activation.