[Chemotherapy of prostatic cancer].
CDDP combined chemotherapy was performed in 55 cases out of 229 prostatic cancer patients who were treated in Nara Medical University and Nara Prefectural Nara Hospital between January 1979 and August 1989. The previously untreated 33 patients received chemotherapy with anti-androgen treatment as an initial treatment, as well as 7 cases of unresponsive to antiandrogen treatment, 14 relapsing cases and one case with recurrence after total prostatectomy. The major regimens of chemotherapy were cis-diammine dichloroplatinum (CDDP) alone in 16 cases, PVB regimen (bleomycin or peplomycin + vincristine + CDDP) in 19 cases, and CAP regimen (cyclophosphamide + adriamycin + CDDP) in 16 cases. Complete response was not achieved or partial response was observed in 20 cases (34%), no change was seen in 20 cases (34%), and progression was seen in 19 cases (32%). Among each evaluable lesion, effects (CR + PR) were observed in 40% in the prostate, in 18% in the bone lesions, in 44% in the soft tissue lesions, and in 42% in the prostatic tumor marker. The 7-year survival rate of the chemotherapy group (35.6%) was better than that of the antiandrogen treatment group (26.6%) in stage D patients, but was not significant statistically When evaluated by the regimen, a partial response was observed in 56% of CDDP alone, in 21% of PVB regimen, and in 38% of the CAP regimen. However, there was no significant difference in survival rate among the regimens. As an adverse effect, myelosuppression and renal toxicity seemed to be dose limiting factors of CDDP combined chemotherapy for advanced prostatic cancer patients.


The regulation of cellular transcription by Simian virus 40 large T-antigen.
The transforming protein of Simian virus 40 (SV40), large T-antigen, regulates transcription both positively and negatively during the productive infection cycle. We have isolated a number of cellular genes which are expressed at elevated levels in SV40-transformed cells and have used these to study the mechanism or mechanisms by which the viral transforming protein regulates cellular gene expression. Small RNAs homologous to the mouse B2 repetitive sequence family are found at higher levels in transformed cells than in normal cells and we have shown that pure large T-antigen stimulates transcription of such repeats by RNA polymerase III. A class I major histocompatibility complex (MHC) gene is also activated as a result of SV40 transformation and we have used DNA-mediated gene transfer to study how this gene is regulated by large T-antigen.


Quantitation of red cell-bound IgG, IgA, and IgM in patients with autoimmune hemolytic anemia and blood donors by enzyme-linked immunosorbent assay.
This paper describes an enzyme immunoassay for the quantitative determination of IgG, IgA, and IgM immunoglobulins on RBCs. Ether eluates made from RBCs were followed by an enzyme-linked immunosorbent assay of immunoglobulin concentration. Calibration curves were derived from immunoglobulin standards and the number of molecules of each isotype per RBC was calculated. The assay was carried out in 200 healthy blood donors and 62 patients with warm autoimmune hemolytic anemia (AIHA), two of them with a negative DAT. For healthy blood donors, mean values were 58 IgG, 16 IgA, and 3 IgM molecules per RBC. For patients with a positive DAT, the mean values were 3435 IgG, 157 IgA, and 69 IgM molecules per RBC. An increased level of IgA was found in 12 patients without IgA autoantibodies demonstrable in RBC eluates. Increased IgG levels were also observed in patients with a negative DAT and, in one case, an increased level of IgA was also found. The enzyme-linked immunosorbent assay using ether eluates is a sensitive method for quantitating RBC autoantibodies in patients with AIHA as well as immunoglobulins bound to RBCs in healthy individuals.


Long-term nutrient enrichment decouples predator and prey production.
Increased nutrient mobilization by human activities represents one of the greatest threats to global ecosystems, but its effects on ecosystem productivity can differ depending on food web structure. When this structure facilitates efficient energy transfers to higher trophic levels, evidence from previous large-scale enrichments suggests that nutrients can stimulate the production of multiple trophic levels. Here we report results from a 5-year continuous nutrient enrichment of a forested stream that increased primary consumer production, but not predator production. Because of strong positive correlations between predator and prey production (evidence of highly efficient trophic transfers) under reference conditions, we originally predicted that nutrient enrichment would stimulate energy flow to higher trophic levels. However, enrichment decoupled this strong positive correlation and produced a nonlinear relationship between predator and prey production. By increasing the dominance of large-bodied predator-resistant prey, nutrient enrichment truncated energy flow to predators and reduced food web efficiency. This unexpected decline in food web efficiency indicates that nutrient enrichment, a ubiquitous threat to aquatic ecosystems, may have unforeseen and unpredictable effects on ecosystem structure and productivity.


PET evaluation of soft-tissue masses with fluorine-18 fluoro-2-deoxy-D-glucose.
Positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) was performed in 19 patients referred for clinical evaluation of soft-tissue masses. These patients had 20 different lesions and had been evaluated previously with computed tomography (CT) and/or magnetic resonance (MR) imaging. The diagnoses were subsequently confirmed with open biopsy or excision (19 lesions) or by clinical and radiographic follow-up (one lesion). Semiquantitative assessment of FDG accumulation (differential uptake ratio) within the suspected tumor helped correctly separate the 10 malignant tumors from the 10 benign lesions. In contrast, a simple ratio of FDG uptake within the suspected tumor to that within comparable normal soft tissue was less successful in helping make this distinction, with overlap in 12 of the 20 cases. Careful comparison with findings from other available imaging studies is essential for accurate interpretation of PET studies of soft-tissue masses, but in many cases, PET may be a useful adjunct in the preoperative evaluation of suspected soft-tissue tumors, yielding valuable information that is not provided with CT or MR imaging.


[Chlamydia trachomatis in pregnant women in the county of Vestsjaelland. Prevalence, prevention of perinatal transmission and cost-effectiveness of screening].
The prevalence of genital Chlamydia trachomatis (CT) in pregnant women and the perinatal transmission after treatment was investigated. An analysis of the cost-effectiveness of introducing a screening program among women at risk of having CT was made. Out of 339 pregnant women 2.9% had cervical CT. CT-positive women were treated with erythromycin. CT-positive women were significantly younger than CT-negative women and the odds ratio (OR) of having CT if nulliparous was 3.35. The CT-prevalence was 6.6% among women younger than 25 years and 1.6% among women 25 years or older (p = 0.0163). OR of having CT if younger than 25 years was 4.3. The young women were significantly younger at sexual début. None of the children of women treated for CT during pregnancy developed neonatal CT-conjunctivitis. The screening of women younger than 25 years was considered to be cost-effective. It is concluded that women younger than 25 years are at risk of having CT. Treatment of CT-positive women with erythromycin during pregnancy seems to be effective in eradicating this microorganism and thus preventing perinatal transmission and neonatal CT-conjunctivitis. It therefore seems rational to screen all pregnant women under the age of 25 years for cervical CT, especially in high risk areas.


In situ fixation of the slipped capital femoral epiphysis with a single screw.
We made a retrospective analysis of a consecutive series of patients with slipped capital femoral epiphyses (SCFE) surgically treated at the Shriners Hospitals for Crippled Children at Lexington, Kentucky. The clinical outcome was correlated to the number of pins and the incidence of chondrolysis, ischemic necrosis, and progressive slipping after the initial fixation. An evaluation made of the Walters-Simon theoretic pin penetration formula was of no value in this series. We compiled results in the medical literature and compared them with ours; all information indicated that a single pin through an anterior portal significantly reduces complications and provides reliable fixation. However, ischemic necrosis still occurs in the unstable slip, although at a lesser rate than in cases treated with multiple pin fixation.


Near-Infrared Photoluminescence and Electrochemiluminescence from a Remarkably Simple Boron Difluoride Formazanate Dye.
A boron difluoride formazanate dye that exhibits near-infrared photoluminescence and electrochemiluminescence was produced via a straightforward two-step synthesis. Examination of its solid-state structure suggested that the N-aryl substituents have significant quinoidal character, which narrows the S1 -S0 energy gap and leads to the unique optoelectronic properties observed. Cyclic voltammetry studies revealed two oxidation waves and two reduction waves that were electrochemically reversible. Electrochemiluminescence properties were examined in the presence of tri-n-propylamine, leading to maximum intensity at 910 nm, at least 85 nm (1132 cm-1 ) red-shifted compared to all other organic dyes. This work sets the stage for the development of future generations of dyes for emerging applications, including single-cell imaging, that require near-infrared photoluminescence and electrochemiluminescence.


Psychiatric Predictors of Long-term Transplant-Related Outcomes in Lung Transplant Recipients.
Long-term survival after lung transplantation remains poor, yet modifiable risk factors for late-term morbidity and mortality have yet to be identified. Because psychiatric disorders increase risk for poor health outcomes in many nontransplant chronic disease populations, lung recipients with depression or anxiety before or early after transplantation may be at heightened risk for late-term transplant-related morbidity and mortality. Among 178 patients from a prospective study of mental health after lung transplantation, we identified 1-year survivors and examined whether they experienced major depression or anxiety disorders during that year as well as before transplantation. We used multivariable Cox regression to examine the relationship between these disorders and risk for subsequent bronchiolitis obliterans syndrome (BOS), mortality and graft loss for up to 15 years posttransplant, controlling for other known risk factors for the outcomes. One hundred fifty-five recipients were studied. Recipients with posttransplant depression had an elevated risk of BOS (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 1.10-3.31), patient death (HR, 1.65; 95% CI, 1.01-2.71) and graft loss (HR, 1.75; 95% CI, 1.06-2.88). A trend toward reduced risk of BOS was observed in recipients with posttransplant anxiety (HR, 0.61; 95%CI, 0.37-1.00). Neither pretransplant disorder was related to risk for any outcome. Early posttransplant depression increases risk for long-term transplant-related morbidity and mortality. Screening to identify depression should therefore be routine in posttransplant care. Although anxiety was not significantly associated with poor outcomes, screening for posttransplant anxiety should also be routine, to reduce patient distress. Research is needed to better understand mechanisms underlying depression-outcome associations.


Increased BCAR1 predicts poor outcomes of non-small cell lung cancer in multiple-center patients.
This study was designed to determine the prognostic value of BCAR1 expression and its associations with clinical-demographical characteristics in multiple centers of non-small cell lung cancer (NSCLC) patients. Gene expression microarray (mRNA) of 77 adenocarcinomas from Mayo Clinic, RNA-sequencing of 508 NSCLC from The Cancer Genome Atlas (TCGA), and immunohistochemistry stain of BCAR1-protein expression in 150 cases from Daping Hospital were included in the study. The association of mRNA or protein expression with patient clinical characteristics and overall survival was assessed in each dataset. We also predicted microRNAs (miRNA) that target BCAR1 using bioinformatics prediction tools and evaluated miRNA expression patterns with BCAR1 expression in miRNA-sequencing data of 74 lung cancer cases from TCGA dataset. In the Mayo Clinic dataset, a higher BCAR1-mRNA level correlated significantly with more advanced tumor-stage and lymphatic metastasis. Similar changes were observed in the TCGA RNA-seq dataset. Additionally, higher BCAR1-mRNA levels predicted poorer survival in adenocarcinoma and squamous carcinoma from the TCGA dataset. The protein levels in the adenocarcinoma cases with lymphatic metastasis were significantly higher than of those without metastasis. Tumor tissues demonstrated remarkably higher levels of protein compared with matched normal tissues although there was no significant difference in BCAR1-mRNA expression between tumor and matched normal tissues was detected. In miRNAs that were downregulated in the tumors, Let-7f-2 and miR-22 differed the most (P < 0.001 and P = 0.007, respectively). We confirmed that increased BCAR1 expression predicts poorer prognosis in NSCLC. We postulate that mRNA-protein decoupling of BCAR1 may be a result of reduced inhibition of specific miRNAs in tumor tissues, which warrants further study.


Identification and modelling of fast and slow Ih current components in vestibular ganglion neurons.
Previous experimental data indicates the hyperpolarization-activated cation (Ih) current, in the inner ear, consists of two components [different hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits] which are impossible to pharmacologically isolate. To confirm the presence of these two components in vestibular ganglion neurons we have applied a parameter identification algorithm which is able to discriminate the parameters of the two components from experimental data. Using simulated data we have shown that this algorithm is able to identify the parameters of two populations of non-inactivated ionic channels more accurately than a classical method. Moreover, the algorithm was demonstrated to be insensitive to the key parameter variations. We then applied this algorithm to Ih current recordings from mouse vestibular ganglion neurons. The algorithm revealed the presence of a high-voltage-activated slow component and a low-voltage-activated fast component. Finally, the electrophysiological significance of these two Ih components was tested individually in computational vestibular ganglion neuron models (sustained and transient), in the control case and in the presence of cAMP, an intracellular cyclic nucleotide that modulates HCN channel activity. The results suggest that, first, the fast and slow components modulate differently the action potential excitability and the excitatory postsynaptic potentials in both sustained and transient vestibular neurons and, second, the fast and slow components, in the control case, provide different information about characteristics of the stimulation and this information is significantly modified after modulation by cAMP.


[Detection of free cancer cells in peritoneal cavity in patients surgically treated for gastric adenocarcinoma].
Peritoneal metastasis is a leading cause of therapeutic failure after an operative treatment of patients with gastric adenocarcinoma. Free cancer cells might induce or indicate an early peritoneal seeding with a subsequent peritoneal metastasis. The aim of this study was to determine the frequency of the presence of free cancer cells in the peritoneal cavity in the patients surgically treated for gastric adenocarcinoma, and its relation to certain clinical, operative and pathohistological paramethers. Inside a period from April 2000, and April 2004, the total of 100 patients underwent intraoperative peritoneal lavage for cytological examination. Immediately after the laparotomy, 200 ml physiologic saline, heated to 37 degrees C, was introduced into the abdominal cavity, mannualy dispersed and collected from the region around the gastric tumor and the pouch of Douglas. The nucleated cell layer was smeared on four glass slides for every patient and dyed with May-Grünwald-Giemsa stain. The cytological findings were defined as positive or negative according to the presence of cancer cells. The frequency of positive cytological findings was compared to the location and the diameter of the cancer, pathohistological type of carcinoma, pathohistological stage of the disease, lymph node and the liver and/or peritoneal metastases and the type of surgical procedure. Free cancer cells were found in 24 (24%) of the patients, while in 76 (76%) of them cytological findings were negative. A statistically highly significant difference (p < or = 0.001) in the frequency of positive cytological finding was found between the groups of patients with and without cancer invasion of serosa, with cancer diameters > 5 cm and < or = 5 cm, in the stage of disease I, II and III, IV, with macroscopically present and without metastases, with re section and D2 lymphadenectomy and palliative procedure. Free cancer cells were statistically more frequently (p < or = 0.05) detected in the patients with lymph nodes metastases comparing to the patients with out lymph nodes involvement. The results of the univariate analysis showed that the cancer diameter > 5 cm, tumor invasion of serosa, pathohistological stage of the disease III and IV and macroscopically visible metastases were the most important risk factors for the free cancer cells detection. Peritoneal lavage cytology was shown to be a useful tool for the detection of the group of patients with greatest risk of peritoneal dissemination. The frequency of positive cytological findings was highly associated with the diameter of the tumor and the cancer invasion of serosa. Cytological examination of peritoneal lavage fluid improved the accuracy of staging and selection of patients who might have benefit from neoadjuvant chemotherapy.


Molecular cytogenetic identification of new wheat-rye 6R, 6RS, and 6RL addition lines with resistance to stripe rust and powdery mildew.
Stripe rust and powdery mildew are devastating diseases that have severe effects on wheat production. Introducing resistant genes/loci from wheat-related species into the wheat genome is an important method to improve wheat resistance. Rye (Secale cereale L.) is a cross-pollinating plant and is the most important related species for wheat genetic improvement. In this study, we developed three 6RS ditelosomic addition lines, three 6RL ditelosomic addition lines, and two 6R disomic addition lines by crossing common wheat cultivar Chuannong 25 and rye inbred line QL2. The chromosome composition of all new lines was confirmed by non-denaturing fluorescence in situ hybridization (ND-FISH) and molecular marker analyses. Disease responses to different Puccinia striiformis f. sp. tritici (Pst) races and Blumeria graminis f. sp. tritici (Bgt) isolates and cytogenetic analysis showed that the resistance of the new lines was derived from the rye chromosome 6R of QL2, and both arms (6RS and 6RL) may harbor resistance genes against Pst and Bgt. These new lines could be used as a promising bridging parent and valuable genetic resource for wheat disease resistance improvement.


Problems of long-term informed consent.
This study addresses problems arising with informed consent for long-term maintenance pharmacotherapy. Obtaining patient consent to neuroleptic treatment, with the risk of tardive dyskinesia, has raised questions about long-term recall and the competence of psychiatric patients as a special population. The subjects were 32 adult outpatients, 16 were followed in the psychiatric clinic and 16 in the rheumatology, pulmonary, and neurology clinics. Structured interviews with these patients dealt with knowledge about relevant short-term and long-term medication side effects. Interview results were used to compare psychiatric and medical groups with respect to overall levels of comprehension. Two results were striking. 1. There was a remarkable similarity in the degree of comprehension between psychiatric and medical outpatient groups; this suggests that psychiatric patients need not be considered any less competent than medical outpatients in assimilating necessary medication information. 2. Patients in both groups were knowledgeable about short-term side effects, usually as a consequence of personal experience with them. However, their knowledge was consistently inadequate with regard to potential long-term side effects from their maintenance medication. Current informed consent doctrine may presume a degree of recall and comprehension beyond the capabilities of most patients. The development of an appropriate doctor-patient relationship that reconciles the need for consent with patient limitations remains an important challenge for clinicians.


Alarm substance recognition and predator avoidance by chinook salmon (Oncorhynchus tschawytscha) following exposure to an organophosphate pesticide.
The sense of smell in fish is thought to be important for behaviors associated with alarm scent recognition and predator avoidance. Olfactory function of juvenile chinook salmon was evaluated in two separate experiments following 2-h immersion exposures to 0, 1, 10, or 100 microg diazinon/L. In the first test system, groups of 10 salmon were transferred to the prechoice zone of a Y-maze fluviarium with parallel streams of water. A dilute alarm scent composed of either chinook skin extract or L-serine was pumped into the water supply of one arm. Fish were allowed to choose either upstream arm by raising a containment screen for 10 min, then their positions were photographed and the screen lowered. In the second test system the relationship of diazinon exposure to predation susceptibility was directly examined by transferring groups of 20 salmon (10 diazinon-exposed, 10 control) to troughs containing a protective cover. These salmon were given two olfactory warnings by delivering conspecific skin extract to both their transfer container and the predation tank they entered. After a 2-min prey acclimation period, larger predator rainbow trout were allowed access to the downstream section of the tank containing the test salmon. The combined fish were observed until approximately 50% of the prey fish had been consumed. Statistical comparisons indicated that although the salmon did avoid the water streams containing alarm scents, none of the diazinon exposure levels resulted in significantly different outcomes from the controls (alpha=0.05) in either the two-choice maze study or the predation study. Possible environmental and population implications are discussed in light of related olfaction and diazinon studies.


Seasonal shift of diet in bank voles explains trophic fate of anthropogenic osmium?
Diet shifts are common in mammals and birds, but little is known about how such shifts along the food web affect contaminant exposure. Voles are staple food for many mammalian and avian predators. There is therefore a risk of transfer of contaminants accumulated in voles within the food chain. Osmium is one of the rarest earth elements with osmium tetroxide (OsO4) as the most toxic vapor-phase airborne contaminant. Anthropogenic OsO4 accumulates in fruticose lichens that are important winter food of bank voles (Myodes glareolus). Here, we test if a) anthropogenic osmium accumulates in bank voles in winter, and b) accumulation rates and concentrations are lower in autumn when the species is mainly herbivorous. Our study, performed in a boreal forest impacted by anthropogenic osmium, supported the hypotheses for all studied tissues (kidney, liver, lung, muscle and spleen) in 50 studied bank voles. In autumn, osmium concentrations in bank voles were even partly similar to those in the graminivorous field vole (Microtus agrestis; n=14). In autumn but not in late winter/early spring, osmium concentrations were generally negatively correlated with body weight and root length of the first mandible molar, i.e. proxies of bank vole age. Identified negative correlations between organ-to-body weight ratios and osmium concentrations in late winter/early spring indicate intoxication. Our results suggest unequal accumulation risk for predators feeding on different cohorts of bank voles.


Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications.
Acute myeloid leukemia (AML) is a heterogeneous disease that is characterized by distinct cytogenetic or genetic abnormalities. Recent discoveries in cancer epigenetics demonstrated a critical role of epigenetic dysregulation in AML pathogenesis. Unlike genetic alterations, the reversible nature of epigenetic modifications is therapeutically attractive in cancer therapy. DNA methylation is an epigenetic modification that regulates gene expression and plays a pivotal role in mammalian development including hematopoiesis. DNA methyltransferases (DNMTs) and Ten-eleven-translocation (TET) dioxygenases are responsible for the dynamics of DNA methylation. Genetic alterations of DNMTs or TETs disrupt normal hematopoiesis and subsequently result in hematological malignancies. Emerging evidence reveals that the dysregulation of DNA methylation is a key event for AML initiation and progression. Importantly, aberrant DNA methylation is regarded as a hallmark of AML, which is heralded as a powerful epigenetic marker in early diagnosis, prognostic prediction, and therapeutic decision-making. In this review, we summarize the current knowledge of DNA methylation in normal hematopoiesis and AML pathogenesis. We also discuss the clinical implications of DNA methylation and the current therapeutic strategies of targeting DNA methylation in AML therapy.


Case-mix indexes: do they adversely affect some hospitals?
The use of 1981 case mix indexes in setting the hospital-specific payment amounts under PPS appears to treat a number of hospitals arbitrarily. Due to random variation, data errors, and changes in services, the use of these indexes will sometimes produce clearly unreasonable results. Therefore, hospitals should review the effect of the indexes, and if adversely affected, they should properly note their objection to their use to preserve appeal rights when filing PPS cost reports.


Repurposing Riociguat to Target a Novel Paracrine Nitric Oxide-TRPC6 Pathway to Prevent Podocyte Injury.
Increased expression and activity of the Ca2+ channel transient receptor potential channel 6 (TRPC6) is associated with focal segmental glomerulosclerosis, but therapeutic strategies to target TRPC6 are currently lacking. Nitric oxide (NO) is crucial for normal glomerular function and plays a protective role in preventing glomerular diseases. We investigated if NO prevents podocyte injury by inhibiting injurious TRPC6-mediated signaling in a soluble guanylate cyclase (sGC)-dependent manner and studied the therapeutic potential of the sGC stimulator Riociguat. Experiments were performed using human glomerular endothelial cells and podocytes. Podocyte injury was induced by Adriamycin incubation for 24 h, with or without the NO-donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP), the sGC stimulator Riociguat or the TRPC6 inhibitor Larixyl Acetate (LA). NO and Riociguat stimulated cGMP synthesis in podocytes, decreased Adriamycin-induced TRPC6 expression, inhibited the Adriamycin-induced TRPC6-mediated Ca2+ influx and reduced podocyte injury. The protective effects of Riociguat and NO were blocked when sGC activity was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or when TRPC6 activity was inhibited by LA. Our data demonstrate a glomerular (e)NOS-NO-sGC-cGMP-TRPC6 pathway that prevents podocyte injury, which can be translated to future clinical use by, e.g., repurposing the market-approved drug Riociguat.


Engineering mouse chromosomes with Cre-loxP: range, efficiency, and somatic applications.
Chromosomal rearrangements are important resources for genetic studies. Recently, a Cre-loxP-based method to introduce defined chromosomal rearrangements (deletions, duplications, and inversions) into the mouse genome (chromosome engineering) has been established. To explore the limits of this technology systematically, we have evaluated this strategy on mouse chromosome 11. Although the efficiency of Cre-loxP-mediated recombination decreases with increasing genetic distance when the two endpoints are on the same chromosome, the efficiency is not limiting even when the genetic distance is maximized. Rearrangements encompassing up to three quarters of chromosome 11 have been constructed in mouse embryonic stem (ES) cells. While larger deletions may lead to ES cell lethality, smaller deletions can be produced very efficiently both in ES cells and in vivo in a tissue- or cell-type-specific manner. We conclude that any chromosomal rearrangement can be made in ES cells with the Cre-loxP strategy provided that it does not affect cell viability. In vivo chromosome engineering can be potentially used to achieve somatic losses of heterozygosity in creating mouse models of human cancers.


Magnitude of phonetic distinction predicts success at early word learning in native and non-native accents.
Although infants perceptually attune to native vowels and consonants well before 12 months, at 13-15 months, they have difficulty learning to associate novel words that differ by their initial consonant (e.g., BIN and DIN) to their visual referents. However, this difficulty may not apply to all minimal pair novel words. While Canadian English (CE) 15-month-olds failed to respond to a switch from the newly learned word DEET to the novel non-word DOOT, they did notice a switch from DEET to DIT (Curtin et al., 2009). Those authors argued that early word learners capitalize on large phonetic differences, seen in CE DEET-DIT, but not on smaller phonetic differences, as in CE DEET-DOOT. To assess this hypothesis, we tested Australian English (AusE) 15-month-olds, as AusE has a smaller magnitude of phonetic difference in both novel word pairs. Two groups of infants were trained on the novel word DEET and tested on the vowel switches in DIT and DOOT, produced by an AusE female speaker or the same CE female speaker as in Curtin et al. (2009). If the size of the phonetic distinction plays a more central role than native accent experience in early word learning, AusE children should more easily recognize both of the unfamiliar but larger CE vowel switches than the more familiar but smaller AusE ones. The results support our phonetic-magnitude hypothesis: AusE children taught and tested with the CE-accented novel words looked longer to both of the switch test trials (DIT, DOOT) than same test trials (DEET), while those who heard the AusE-accented tokens did not notice either switch. Implications of our findings for models of early word learning are discussed.


An Observational Research Study to Evaluate the Impact of Breakthrough Cancer Pain on the Daily Lives and Functional Status of Patients.
Breakthrough cancer pain (BTcP) is common, resulting in significant physical and psychosocial morbidity. We assessed the impact of BTcP on 81 cancer patients attending Irish specialist palliative care services. BTcP occurred up to twice daily in 24 (30%) and 3-4 times daily in 57 (70%) of cases. Median scores for the 'worst' and 'least' pains in the previous 24 hours were 7 and 2/10 respectively. Pain lasted < 15 minutes in 19 (23.5%), 15-30 minutes in 25 (30.8%), 30-60 minutes in 18 (22.2%) and > 60 minutes in 19 (23.5%) of patients. BTcP had a negative impact on general activity, mood, walking ability, work, relations with others, sleep and overall enjoyment of life. BTcP increased anxiety, depression, anger, isolation, financial difficulties and an inability to undergo cancer treatments. Systematic assessment of BTcP should form an integral part of every oncology/palliative medicine assessment. Once identified, BTcP should be managed assiduously.


Comparison of the low-density lipoprotein cholesterol target value and the preventive effect of statins in elderly patients and younger patients.
To assess whether the low-density lipoprotein cholesterol (LDL-C) target value and preventive effect of statins are different between elderly and younger patients. We investigated 304 patients with previous percutaneous coronary intervention who underwent coronary angiography from January 2007 to December 2016 for examination of recurrent ischemia beyond the early restenosis. Patients were classified into two groups: age ≥ 75 years (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships between the achieved LDL-C level, incidence of late coronary events, and the effectiveness of statins were evaluated. During follow-up, 179 patients underwent late coronary revascularization. Recurrent ischemia presenting as acute coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis revealed that in the younger group, recurrent ACS was significantly lower in patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100 mg/dL (P = 0.035); however, there was no difference between these in the elderly group (P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL-C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C ≥ 100 mg/dL in the elderly group (P = 0.033). Statin use was associated with decreased recurrent ACS (P = 0.005); moreover, only using statins was an independent predictor in the elderly group (HR: 0.375; P = 0.007). Strict control of LDL-C to < 70 mg/dL was effective for reducing the incidence of recurrent ACS in younger patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese elderly patients.


Direction and reliability of head tilt in humans.
It has been proposed that asymmetry in the inner ear underlies various manifestations of brain-behaviour asymmetry in the human. Specifically, Previc (1991) argued that an otolith imbalance manifests itself in an asymmetrical head posture, and later (1994) suggested that head tilt may be consonant with other measures of human laterality. The present study tested the reliability of head tilt across days and assessed its relationship with handedness, footedness, and eyedness. As in Previc's earlier studies, a majority of our subjects tilted rightward. Head tilt proved to be highly stable across days but was not correlated with the other laterality measures. These findings suggest that head tilt may reflect an underlying asymmetric substrate that appears not to be directly related to other measures of cerebral hemispheric dominance.


14N NMR of lipid bilayers: effects of ions and anesthetics.
The interaction of divalent and trivalent metal cations, ferricyanide, a lipophilic ion (tetraphenylborate), and a local anesthetic (tetracaine) with the phosphocholine head group of egg lecithin was investigated by using wide-line 14N and 31P NMR. Measurements of the 14N quadrupolar splittings in the presence of a variety of perturbing agents demonstrated that the 14N NMR technique can be used to directly monitor ion or anesthetic binding. The 14N quadrupolar splitting (delta nu Q) is a measure of the order parameter of the C beta-N bond segment, and changes in delta nu Q as large as 3.5 kHz were observed. Moreover, a comparison of the changes in the quadrupolar splittings induced by the binding of ions or anesthetics provided a sensitive method of discriminating between these perturbing agents in their ability to alter the orientational order of the C beta-N bond segment of the phosphocholine moiety. Without exception, addition of metal ions or anesthetics always resulted in a decrease of the 14N delta nu Q. This reduction reflects a change in the average orientation or degree of motional averaging at the C beta-N bond segment position. In the case of metal ion binding, the strength of the interaction increased with the charge of the metal ion in the order Ca2+ less than Ln3+, in agreement with a previous 2H NMR study [Akutsu, H., & Seelig, J. (1981) Biochemistry 20, 7366-7373].(ABSTRACT TRUNCATED AT 250 WORDS)


Basic investigations on the performance of a normoxic polymer gel with tetrakis-hydroxy-methyl-phosphonium chloride as an oxygen scavenger: reproducibility, accuracy, stability, and dose rate dependence.
Magnetic resonance (MR)-based polymer gel dosimetry using normoxic polymer gels, represents a new dosimetric method specially suited for high-resolution three-dimensional dosimetric problems. The aim of this study was to investigate the dose response with regard to stability, accuracy, reproducibility, and the dose rate dependence. Tetrakis-hydroxy-methyl-phosphonium chloride (THPC) is used as an oxygen scavenger, and methacrylic acid as a monomer. Accuracy, reproducibility, and dose resolution were determined for MR protocols at low spatial resolution (typical for clinical scanners), medium, and microimaging-resolution protocols at three different dose levels. The dose-response stability and preirradiation-induced variations in R2, related to the time interval between preparation and irradiation of the polymer gel, were investigated. Also postirradiation stability of the polymer gel was considered. These experiments were performed using a 60Co beam (E = 1.2 MV) in a water phantom. Moreover, we investigated the dose rate dependence in the low, medium, and saturation dose region of the normoxic polymer gel using a linear accelerator at photon energy of 25 MV. MR scanning was performed on a 3 T whole body scanner (MEDSPEC 30/80, BRUKER BIOSPIN, Ettlingen, Germany) using several coils and different gradient systems adapted to the acquired spatial resolution investigated. For T2-parameter selective imaging and determination of the relaxation rate R2 = 1/T2, a multiple spin echo sequence with 20 equidistant echoes was used. With regard to preirradiation induced variations R2 increases significantly with the increasing time interval between the polymer gel preparation and irradiation. Only a slight increase in R2 can be observed for varying the postirradiation-time solely. The dose reproducibility at voxel volumes of about 1.4 x 1.4 x 2 mm3 is better than 2%. The accuracy strongly depends on the calibration curve. THPC represents a very effective oxygen scavenger in methacrylic acid and gelatin. Polymer gels containing THPC offer high sensitivity to dose but their dose response also strongly depends on dose rate in the medium and high dose region.


Sociobehavioral factors associated with caries increment: a longitudinal study from 24 to 36 months old children in Thailand.
The aim of this study is to investigate sociobehavioral risk factors from the prenatal period until 36 months of age, and the caries increment from 24 to 36 months of the child in Thailand. The data utilized in this study come from the prospective cohort study of Thai children (PCTC) from prenatal to 36 months of the child in Mueang Nan district, Northern Thailand. The total sample size recruited was 783 infants. The sample size with dental caries data was 603 and 597, at 24 months and at 36 months, respectively. The sample size of having two assessment points with a dental examination (at 24 months and at 36 months) was 597. Results indicate that the caries increment was 52.9%, meaning from 365 caries free children at 24 months 193 had developed dental caries at 36 months. The prevalence of dental caries was 34.2% at 24 months (n = 206) and 68.5% at 36 months of age (n = 409). In bivariate analysis, higher education of the mother, lower household income, bottle feeding of the infant, frequent sweet candy consumptions, and using rain or well water as drinking water were associated with dental caries increment, while in multivariate conditional logistic regression analysis lower household income, higher education of the mother, and using rain or well water as drinking water remained associated with dental caries increment. In conclusion, a very significant increase in caries development was observed, and oral health may be influenced by sociobehavioural risk factors.


KATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy.
ATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the KATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy. PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. KATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites.DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence. We identified Kir6.2/SUR1 and Kir6.2/SUR2 KATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of KATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy KATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls.Because KATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of KATP channels as targets of therapies against neuropathic pain and neurodegeneration.


Relationship of reported clinical features of pre-eclampsia and postpartum haemorrhage to demographic and other variables.
Maternal death and disability remain significant problems in developing countries and are predominantly caused by preeclampsia and postpartum haemorrhage. The diagnostic criteria for preeclampsia and postpartum haemorrhage require medical technologies not readily available in underdeveloped areas. To determine the correlates of pre-eclampsia and postpartum haemorrhage using symptoms in a rural setting. This was a cross-sectional study in which 577 women from the Kwahu South District of the Eastern Region of Ghana completed questionnaires that sought for signs and symptoms of pre-eclampsia and postpartum haemorrhage in their current or prior pregnancies. The study was conducted over a period of two months, symptoms of pre-eclampsia assessed included headache, visual disturbance, urination, breathing, leg swelling and seizures. For postpartum haemorrhage, the following features were assessed: placenta delivery, length of labour, difficult delivery of placenta, lacerations associated with delivery, size of newborn, headache, visual disturbance and amount of vaginal bleeding. There was a significant association between education and the number of signs and symptoms of preeclampsia, (Χ² =9.059, =0.018; OR no education vs >7 years=6.8). Mothers with no education were about seven times more likely to have all six signs and symptoms of preeclampsia than those with seven or more years of education. There was no significant association between education and postpartum haemorrhage, (Χ² = 1.835, = 0.400). However, the OR of 1.59, indicated an inverse association between the two variables. The high number of symptoms associated with preeclampsia among women with no formal education strongly supports the need for educational outreach and basic prenatal care in rural Ghana.


Time-dependent quantum dynamics study of the F + C2H6 → HF + C2H5 reaction.
The reaction probabilities, integral cross sections, energy efficiency and rate constants are investigated for the F + C2H6 reaction using the quantum reaction dynamics, wave packet method. The ground-state integral cross section calculated using a six-degree-of-freedom approach is in very good agreement with the quasi-classical trajectory results. We find that the H-CH2CH3 stretching motion has the largest enhancement to reactivity, followed by the H-CH2-CH3 bending motion. However, the stretching motion between CH2 and CH3 slightly hinders the reactivity. The energy-form efficacy based on an equal amount of total energy shows that translational energy is more effective in enhancing the reactivity than vibrational energy of the H-CH2CH3 stretching motion at a relatively lower translational energy, while the reverse is true at a relatively high translational energy. An energy-shifting method is employed to calculate the full-dimensional rate constants. The quantum rate constants agree well with one of the two main experimental measurements, and the activation energy has an excellent agreement with the one calculated using canonical variational transition-state theory.


Myosin heavy chain isoforms in human laryngeal muscles: an expression study based on gel electrophoresis.
Laryngeal muscles in mammals are involved in highly specialized functions such as control of air passage, sphincter for airway protection and phonation. In this study, we aimed to assess whether such specialized functions are accompanied by specific distributions of fibre types. To this end, we studied the expression of the isoforms of the heavy subunit of myosin, myosin heavy chain (MyHC), which are considered the molecular markers of fibre types. The pattern of MyHC isoform expression was determined in 5 intrinsic laryngeal muscles: tensors as thyroarytenoid (TA), vocal (Vo), cricothyroid (CT), adductors as transverse arytenoid or interaytenoid (IA), and abductors as posterior cricoarytenoid (PCA), and 2 extrinsic muscles such as thyropharingeal (TPh) and cricopharingeal (CrPh). Muscles were sampled in 14 patients (11 males and 3 females, age 55-75 years) subjected to laryngectomy. MyHC isoforms were separated by SDS-PAGE and quantified by computer assisted densitometry. The comparison between the proportions of MyHC isoforms showed that: i) the three isoforms expressed in trunk and limb muscles (I, IIA and IIX) were present in all muscles examined, ii) the fast or type II MyHC isoforms were predominant in all muscles, representing 60-70% of the total, with no significant differences with respect to muscle types, iii) an additional isoform (indicated as MyHC L) was present in the muscles of the majority of the subjects and was more abundant in Vo and IA. MyHC L was, however, not found in any muscle of the three female patients and was never found in TA and TPh, iv) a great interindividual variability in MyHC distribution was present in all muscles.


Psychiatric intensive care in acute psychosis.
We have reviewed the development of psychiatric intensive care, focusing on organizational factors and the causes of psychiatric violence, suggesting guidelines for rapid tranquillization. The economics of running a psychiatric intensive care unit were subjected to an analysis of fixed, semi-fixed and variable costs. Variable costs (treatment and patient numbers) were shown to be more open to manipulation and possible cost savings.


Case report: The effective response to pembrolizumab in combination with bevacizumab in the treatment of a recurrent glioblastoma with multiple extracranial metastases.
Multiple extracranial metastases of recurrent glioblastoma are rare and often indicate a very poor prognosis. The main conventional treatments are chemotherapy, radiotherapy, chemoradiotherapy or antiangiogenic therapy. Median overall survival is 2.3 to 6 months after the detection of extracranial metastases, and to date, there is no effective treatment for these patients. Herein, we report a recurrent glioblastoma patient with lung metastasis treated with a combination therapy containing bevacizumab and pembrolizumab due to overexpression of PD-L1 and the absence of driver mutations. The progression-free survival was 11 months from lung metastases to bone metastases. This combination treatment was further used as maintenance therapy for another 11 months after bone metastasis and secondary dorsal metastasis because there was no suitable treatment alternative. The overall survival was 27 months after lung metastases, which is much longer than previously reported cases. To our knowledge, this was the first effective use of bevacizumab plus pembrolizumab in a glioblastoma patient with extracranial metastases. Furthermore, this was the first time that bevacizumab plus pembrolizumab was used as a maintenance treatment in glioblastoma, with 11 months of response. Importantly, we showed that such combination therapy may be a novel and effective therapy for glioblastoma patients with extracranial metastases.


Regulating the electrical behaviors of 2D inorganic nanomaterials for energy applications.
Recent years have witnessed great developments in inorganic 2D nanomaterials for their unique dimensional confinement and diverse electronic energy bands. Precisely regulating their intrinsic electrical behaviors would bring superior electrical conductivity, rendering 2D nanomaterials ideal candidates for active materials in electrochemical applications when combined with the excellent reaction activity from the inorganic lattice. This Concept focuses on highly conducting inorganic 2D nanomaterials, including intrinsic metallic 2D nanomaterials and artificial highly conductive 2D nanomaterials. The intrinsic metallicity of 2D nanomaterials is derived from their closely packed atomic structures that ensure maximum overlapping of electron orbitals, while artificial highly conductive 2D nanomaterials could be achieved by designed methodologies of surface modification, intralayer ion doping, and lattice strain, in which atomic-scale structural modulation plays a vital role in realizing conducting behaviors. Benefiting from fast electron transfer, high reaction activity, as well as large surface areas arising from the 2D inorganic lattice, highly conducting 2D nanomaterials open up prospects for enhancing performance in electrochemical catalysis and electrochemical capacitors. Conductive 2D inorganic nanomaterials promise higher efficiency for electrochemical applications of energy conversion and storage.


Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase.
Apolipoprotein E (apoE) has been implicated in modulating the central nervous system (CNS) inflammatory response. However, the molecular mechanisms involved in apoE-dependent immunomodulation are poorly understood. We hypothesize that apoE alters the CNS inflammatory response by signaling via low-density lipoprotein (LDL) receptors in glia. To address this hypothesis, we used a small bioactive peptide formed from the receptor-binding domain of apoE, apoE peptide (EP), to study LDL receptor signaling in microglia. To model glial activation, we treated primary mouse microglia and the microglial cell line BV2 with lipopolysaccharide (LPS) and studied two inflammatory responses: an increase in nitric oxide production (NO) and a decrease in apoE production. We found that treatment of primary microglia and BV2 cells with EP attenuated LPS-induced NO accumulation and apoE reduction in a dose-dependent manner. Using the receptor-associated protein to block ligand binding to members of the LDL receptor family, we found that EP attenuated both of these LPS-induced inflammatory responses via LDL receptors. We studied two intracellular signaling cascades associated with apoE: c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). LPS induced both ERK and JNK activation, whereas EP induced ERK activation, but drastically reduced JNK activation. Inhibition of JNK with SP600125 reduced LPS-induced NO production and apoE reduction in a dose-dependent manner. Treatment of microglia with suboptimal EP in combination with JNK inhibitor enhanced attenuation of LPS-induced NO production. These data suggest that microglial LDL receptors regulate JNK activation, which is necessary for apoE modulation of the inflammatory response.


Interbacterial Transfer of Carbapenem Resistance and Large Antibiotic Resistance Islands by Natural Transformation in Pathogenic Acinetobacter.
Acinetobacter baumannii infection poses a major health threat, with recurrent treatment failure due to antibiotic resistance, notably to carbapenems. While genomic analyses of clinical strains indicate that homologous recombination plays a major role in the acquisition of antibiotic resistance genes, the underlying mechanisms of horizontal gene transfer often remain speculative. Our understanding of the acquisition of antibiotic resistance is hampered by the lack of experimental systems able to reproduce genomic observations. We here report the detection of recombination events occurring spontaneously in mixed bacterial populations and which can result in the acquisition of resistance to carbapenems. We show that natural transformation is the main driver of intrastrain but also interstrain recombination events between A. baumannii clinical isolates and pathogenic species of Acinetobacter. We observed that interbacterial natural transformation in mixed populations is more efficient at promoting the acquisition of large resistance islands (AbaR4 and AbaR1) than when the same bacteria are supplied with large amounts of purified genomic DNA. Importantly, analysis of the genomes of the recombinant progeny revealed large recombination tracts (from 13 to 123 kb) similar to those observed in the genomes of clinical isolates. Moreover, we highlight that transforming DNA availability is a key determinant of the rate of recombinants and results from both spontaneous release and interbacterial predatory behavior. In the light of our results, natural transformation should be considered a leading mechanism of genome recombination and horizontal gene transfer of antibiotic resistance genes in Acinetobacter baumannii. IMPORTANCE Acinetobacter baumannii is a multidrug-resistant pathogen responsible for difficult-to-treat hospital-acquired infections. Understanding the mechanisms leading to the emergence of the multidrug resistance in this pathogen today is crucial. Horizontal gene transfer is assumed to largely contribute to this multidrug resistance. However, in A. baumannii, the mechanisms leading to genome recombination and the horizontal transfer of resistance genes are poorly understood. We describe experimental evidence that natural transformation, a horizontal gene transfer mechanism recently highlighted in A. baumannii, allows the highly efficient interbacterial transfer of genetic elements carrying resistance to last-line antibiotic carbapenems. Importantly, we demonstrated that natural transformation, occurring in mixed populations of Acinetobacter, enables the transfer of large resistance island-mobilizing multiple-resistance genes.


Understanding the Memory Window Overestimation of 2D Materials Based Floating Gate Type Memory Devices by Measuring Floating Gate Voltage.
The memory window of floating gate (FG) type non-volatile memory (NVM) devices is a fundamental figure of merit used not only to evaluate the performance, such as retention and endurance, but also to discuss the feasibility of advanced functional memory devices. However, the memory window of 2D materials based NVM devices is historically determined from round sweep transfer curves, while that of conventional Si NVM devices is determined from high and low threshold voltages (Vth s), which are measured by single sweep transfer curves. Here, it is elucidated that the memory window of 2D NVM devices determined from round sweep transfer curves is overestimated compared with that determined from single sweep transfer curves. The floating gate voltage measurement proposed in this study clarifies that the Vth s in round sweep are controlled not only by the number of charges stored in floating gate but also by capacitive coupling between floating gate and back gate. The present finding on the overestimation of memory window enables to appropriately evaluate the potential of 2D NVM devices.


Compound Heterozygous VPS13A Variants in a Patient with Neuroacanthocytosis: A Case Report and Review of the Literature.
Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by pathogenic variants of the vacuolar protein sorting 13A (VPS13A). Only a few patients with ChAc have been reported to date, and the variant spectrum of VPS13A has not been completely elucidated. We describe the case of a 36-year-old woman who had been experiencing orofacial dyskinesia since age 30 years. In a genetic study using next-generation sequencing, 2 variants of VPS13A, the nonsense variant c.4411C>T (p.Arg1471Ter) and the splicing variant c.145-2A>T, were identified. The splicing variant c.145-2A>T was newly classified as a pathogenic variant through a literature review. Consequently, the patient was diagnosed with ChAc based on the typical clinical manifestations, laboratory findings, and imaging results.


Prediction of wall motion improvement after coronary revascularization in patients with postmyocardial infarction: diagnostic value of dobutamine stress echocardiography and myocardial contrast echocardiography.
The diagnostic value of dobutamine stress echocardiography, myocardial contrast echocardiography and dipyridamole stress thallium-201 single photon emission computed tomography (SPECT) for predicting recovery of wall motion abnormality after revascularization was evaluated in 13 patients with postmyocardial infarction. Seventeen segments showed severe wall motion abnormalities before revascularization. Nine segments which had relatively good Tl uptake on delayed SPECT images despite severely abnormal wall motion were opacified during myocardial contrast echocardiography, and showed improved wall motion after revascularization. In contrast, three segments which had poor Tl uptake and severely abnormal wall motion were not opacified during myocardial contrast echocardiography, and showed no improvement in wall motion during dobutamine stress echocardiography and after revascularization. The following three findings were assumed to be signs of myocardial viability: 1) good Tl uptake on delayed SPECT images; 2) improved wall motion by dobutamine stress echocardiography; and 3) positive opacification of the myocardium by myocardial contrast echocardiography. Myocardial contrast echocardiography had the highest sensitivity (100%) and negative predictive value (100%). Delayed SPECT images had the highest specificity (100%) and positive predictive value (100%). Dobutamine stress echocardiography had a sensitivity of 83.0%, specificity of 80.0%, positive predictive value of 90.9%, and negative predictive value of 66.7%, respectively. Myocardial contrast echocardiography showed the lowest specificity (60.0%). The techniques of dobutamine stress echocardiography and SPECT, though noninvasive, may underestimate wall motion improvement after revascularization. Further examination by myocardial contrast echocardiography is recommended to assess myocardial viability for determining the indications for coronary revascularization in spite of its invasiveness.


Assessment of in vitro cyto/genotoxicity of sequentially treated electroplating effluent on the human hepatocarcinoma HuH-7 cell line.
The present study compares in vitro toxicity of electroplating effluent after the batch treatment process with that obtained after the sequential treatment process. Activated charcoal prepared from sugarcane bagasse through chemical carbonization, and tolerant indigenous bacteria, Bacillus sp. strain IST105, were used individually and sequentially for the treatment of electroplating effluent. The sequential treatment involving activated charcoal followed by bacterial treatment removed 99% of Cr(VI) compared with the batch processes, which removed 40% (charcoal) and 75% (bacteria), respectively. Post-treatment in vitro cyto/genotoxicity was evaluated by the MTT test and the comet assay in human HuH-7 hepatocarcinoma cells. The sequentially treated sample showed an increase in LC50 value with a 6-fold decrease in comet-assay DNA migration compared with that of untreated samples. A significant decrease in DNA migration and an increase in LC50 value of treated effluent proved the higher effectiveness of the sequential treatment process over the individual batch processes.


Phylogenetic and functional biomakers as indicators of bacterial community responses to mixed-waste contamination.
Few studies have demonstrated changes in community structure along a contaminant plume in terms of phylogenetic, functional, and geochemical changes, and such studies are essential to understand how a microbial ecosystem responds to perturbations. Clonal libraries of multiple genes (SSU rDNA, nirK, nirS, amoA, pmoA, and dsrAB) were analyzed from groundwater samples (n = 6) that varied in contaminant levels, and 107 geochemical parameters were measured. Principal components analyses (PCA) were used to compare the relationships among the sites with respect to the biomarker (n = 785 for all sequences) distributions and the geochemical variables. A major portion of the geochemical variance measured among the samples could be accounted for by tetrachloroethene, 99Tc, No3, SO4, Al, and Th. The PCA based on the distribution of unique biomarkers resulted in different groupings compared to the geochemical analysis, but when the SSU rRNA gene libraries were directly compared (deltaC(xy) values) the sites were clustered in a similar fashion compared to geochemical measures. The PCA based upon functional gene distributions each predicted different relationships among the sites, and comparisons of Euclidean distances based upon diversity indices for all functional genes (n = 432) grouped the sites by extreme or intermediate contaminant levels. The data suggested that the sites with low and high perturbations were functionally more similar than sites with intermediate conditions, and perhaps captured the overall community structure better than a single phylogenetic biomarker. Moreover, even though the background site was phylogenetically and geochemically distinct from the acidic sites, the extreme conditions of the acidic samples might be more analogous to the limiting nutrient conditions of the background site. An understanding of microbial community-level responses within an ecological framework would provide better insight for restoration strategies at contaminated field sites.


Impact of empagliflozin in patients with diabetes and heart failure.
Heart failure (HF) is a common disease with increased risk for mortality and morbidity among patients with type 2 diabetes mellitus (T2DM). Optimal glycemic control in this patient population is challenging as many available therapies can potentially exacerbate symptoms of HF. Empagliflozin is one in a novel class of agents, the sodium glucose co-transporter 2 (SGLT2) inhibitors, that lowers blood glucose by increasing urinary glucose excretion and improves glycemic control and lowers body weight and blood pressure. In the recent EMPA-REG OUTCOME trial, empagliflozin was shown to improve cardiovascular outcomes in patients with T2DM and established cardiovascular risk where it reduced HF hospitalizations and cardiovascular death, with a consistent benefit among patients both with and without baseline HF. Here, we review the empagliflozin data on HF outcomes and discuss potential mechanisms for its benefits in HF with a focus on the potentially significant impact that empagliflozin may have on the care of patients with T2DM and HF in the future.


Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆.
Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.


Comparative analysis of the interaction of HSPs in dendritic cells, macrophages, RGM-1 cells infected by Helicobacter pylori.
Helicobacter pylori may cause chronic gastritis, even gastric cancer, however, antigen-presenting cells (APCs) are most important immune cells involved in the induction and expression of the underlying inflammatory responses to resist H. pylori. To study the interaction of HSPs in dendritic cells (DCs), macrophages and RGM-1 cells infected with H. pylori, HSP-27, HSP-60, HSP-70 and HSP-90 proteins were analyzed in the mucosa tissue or serum of gastritis patients caused by H. pylori, and in cell supernatant of DCs, macrophages, RGM-1 infected by H. pylori, or in above host cells. We found that HSP-27, HSP-60, HSP-70 and HSP-90 decreased in gastric epithelial cells, but increased significantly in DCs, macrophages. Meanwhile, inflammation associated proteins iNOS-2 and COX-2 were participated in the expression of HSPs in the process of host cells defensing against H. pylori infection. These findings contribute to understand the functions of HSP-27, HSP-60, HSP-70 and HSP-90 in H. pylori infection APCs and gastric epithelial cells indicating that HSPs would be diagnostic markers for H. pylori infection.


REM sleep phase preference in the crepuscular Octodon degus assessed by selective REM sleep deprivation.
To determine rapid eye movement (REM) sleep phase preference in a crepuscular mammal (Octodon degus) by challenging the specific REM sleep homeostatic response during the diurnal and nocturnal anticrepuscular rest phases. We have investigated REM sleep rebound, recovery, and documented REM sleep propensity measures during and after diurnal and nocturnal selective REM sleep deprivations. Nine male wild-captured O. degus prepared for polysomnographic recordings. Animals were recorded during four consecutive baseline and two separate diurnal or nocturnal deprivation days, under a 12:12 light-dark schedule. Three-h selective REM sleep deprivations were performed, starting at midday (zeitgeber time 6) or midnight (zeitgeber time 18). Diurnal and nocturnal REM sleep deprivations provoked equivalent amounts of REM sleep debt, but a consistent REM sleep rebound was found only after nocturnal deprivation. The nocturnal rebound was characterized by a complete recovery of REM sleep associated with an augment in REM/total sleep time ratio and enhancement in REM sleep episode consolidation. Our results support the notion that the circadian system actively promotes REM sleep. We propose that the sleep-wake cycle of O. degus is modulated by a chorus of circadian oscillators with a bimodal crepuscular modulation of arousal and a unimodal promotion of nocturnal REM sleep


Crystalline liquid and rubber-like behavior in Cu nanowires.
Via in situ TEM tensile tests on single crystalline copper nanowires with an advanced tensile device, we report here a crystalline-liquid-rubber-like (CRYS-LIQUE-R) behavior in fracturing crystalline metallic nanowires. A retractable strain of the fractured crystalline Cu nanowires can approach over 35%. This astonishing CRYS-LIQUE-R behavior of the fracturing highly strained single crystalline Cu nanowires originates from an instant release of the stored ultralarge elastic energy in the crystalline nanowires. The release of the ultralarge elastic energy was estimated to generate a huge reverse stress as high as ~10 GPa. The effective diffusion coefficient (D(eff)) increased sharply due to the consequent pressure gradient. In addition, due to the release of ultrahigh elastic energy, the estimated concomitant temperature increase was estimated as high as 0.6 Tm (Tm is the melting point of nanocrystalline Cu) on the fractured tip of the nanowires. These factors greatly enhanced the atomic diffusion process. Molecular dynamic simulations revealed that the very high reverse stress triggered dislocation nucleation and exhaustion.


Coffee Consumption Modulates Amoxicillin-Induced Dysbiosis in the Murine Gut Microbiome.
The microbiome is essential for host health, and perturbations resulting from antibiotic use can lead to dysbiosis and disease. Diet can be a powerful modulator of microbiome composition and function, with the potential to mitigate the negative effects of antibiotic use. Thus, it is necessary to study the impacts of diet and drug interactions on the gut microbiome. Coffee is a commonly consumed beverage containing many compounds that have the potential to affect the microbiome, including caffeine, polyphenols, and fiber. We supplemented mice with caffeinated and decaffeinated coffee in conjunction with amoxicillin, and used 16S rRNA amplicon sequencing of fecal samples to investigate changes in diversity and composition of the murine fecal microbiome. We found that antibiotics, regardless of coffee supplementation, caused significant disruption to the murine fecal microbiome, enriching for Proteobacteria, Verrucomicrobia, and Bacteroidetes, but reducing Firmicutes. While we found that coffee alone did not have a significant impact on the composition of the fecal microbiome, coffee supplementation did significantly affect relative abundance metrics in mice treated with amoxicillin. After caffeinated coffee supplementation, mice treated with amoxicillin showed a smaller increase in Proteobacteria, specifically of the family Burkholderiaceae. Correspondingly we found that in vitro, Burkholderia cepacia was highly resistant to amoxicillin, and that it was inhibited by concentrations of caffeine and caffeinated coffee comparable to levels of caffeine in murine ceca. Overall, this work shows that coffee, and possibly the caffeine component, can impact both the microbiome and microbiome members during antibiotic exposure.


Multiple scattering of electromagnetic waves by an aggregate of uniaxial anisotropic spheres.
An exact analytical solution is obtained for the scattering of electromagnetic waves from a plane wave with arbitrary directions of propagation and polarization by an aggregate of interacting homogeneous uniaxial anisotropic spheres with parallel primary optical axes. The expansion coefficients of a plane wave with arbitrary directions of propagation and polarization, for both TM and TE modes, are derived in terms of spherical vector wave functions. The effects of the incident angle α and the polarization angle β on the radar cross sections (RCSs) of several types of collective uniaxial anisotropic spheres are numerically analyzed in detail. The characteristics of the forward and backward RCSs in relation to the incident wavelength are also numerically studied. Selected results on the forward and backward RCSs of several types of square arrays of SiO₂ spheres illuminated by a plane wave with different incident angles are described. The accuracy of the expansion coefficients of the incident fields is verified by comparing them with the results obtained from references when the plane wave is degenerated to a z-propagating and x- or y-polarized plane wave. The validity of the theory is also confirmed by comparing the numerical results with those provided by a CST simulation.


Reliability and Validity of a New Test of Change-of-Direction Speed for Field-Based Sports: the Change-of-Direction and Acceleration Test (CODAT).
Field sport coaches must use reliable and valid tests to assess change-of-direction speed in their athletes. Few tests feature linear sprinting with acute change- of-direction maneuvers. The Change-of-Direction and Acceleration Test (CODAT) was designed to assess field sport change-of-direction speed, and includes a linear 5-meter (m) sprint, 45° and 90° cuts, 3- m sprints to the left and right, and a linear 10-m sprint. This study analyzed the reliability and validity of this test, through comparisons to 20-m sprint (0-5, 0-10, 0-20 m intervals) and Illinois agility run (IAR) performance. Eighteen Australian footballers (age = 23.83 ± 7.04 yrs; height = 1.79 ± 0.06 m; mass = 85.36 ± 13.21 kg) were recruited. Following familiarization, subjects completed the 20-m sprint, CODAT, and IAR in 2 sessions, 48 hours apart. Intra-class correlation coefficients (ICC) assessed relative reliability. Absolute reliability was analyzed through paired samples t-tests (p ≤ 0.05) determining between-session differences. Typical error (TE), coefficient of variation (CV), and differences between the TE and smallest worthwhile change (SWC), also assessed absolute reliability and test usefulness. For the validity analysis, Pearson's correlations (p ≤ 0.05) analyzed between-test relationships. Results showed no between-session differences for any test (p = 0.19-0.86). CODAT time averaged ~6 s, and the ICC and CV equaled 0.84 and 3.0%, respectively. The homogeneous sample of Australian footballers meant that the CODAT's TE (0.19 s) exceeded the usual 0.2 x standard deviation (SD) SWC (0.10 s). However, the CODAT is capable of detecting moderate performance changes (SWC calculated as 0.5 x SD = 0.25 s). There was a near perfect correlation between the CODAT and IAR (r = 0.92), and very large correlations with the 20-m sprint (r = 0.75-0.76), suggesting that the CODAT was a valid change-of-direction speed test. Due to movement specificity, the CODAT has value for field sport assessment. Key pointsThe change-of-direction and acceleration test (CODAT) was designed specifically for field sport athletes from specific speed research, and data derived from time-motion analyses of sports such as rugby union, soccer, and Australian football. The CODAT features a linear 5-meter (m) sprint, 45° and 90° cuts and 3-m sprints to the left and right, and a linear 10-m sprint.The CODAT was found to be a reliable change-of-direction speed assessment when considering intra-class correlations between two testing sessions, and the coefficient of variation between trials. A homogeneous sample of Australian footballers resulted in absolute reliability limitations when considering differences between the typical error and smallest worthwhile change. However, the CODAT will detect moderate (0.5 times the test's standard deviation) changes in performance.The CODAT correlated with the Illinois agility run, highlighting that it does assess change-of-direction speed. There were also significant relationships with short sprint performance (i.e. 0-5 m and 0-10 m), demonstrating that linear acceleration is assessed within the CODAT, without the extended duration and therefore metabolic limitations of the IAR. Indeed, the average duration of the test (~6 seconds) is field sport-specific. Therefore, the CODAT could be used as an assessment of change-of-direction speed in field sport athletes.


Exaggerated natriuresis induced by sodium chloride infusion in essential hypertension is accompanied by an exaggerated urinary 3' 5' guanosine monophosphate excretion.
The effects of an intravenous infusion of physiological saline on plasma atrial natriuretic peptide (ANP), guanosine 3' 5' monophosphate (cGMP) concentrations, and on urinary cGMP and sodium excretion were studied in 13 patients with essential hypertension, class I according to WHO criteria, and in 10 healthy subjects. It was found that the groups did not differ as to basal and infusion-induced plasma ANP and cGMP and basal urinary cGMP and sodium excretion, but the sodium chloride infusion resulted in a significantly greater urinary cGMP and sodium excretion and creatinine clearance in hypertensive than in control subjects. The results of this study demonstrate that patients with essential hypertension respond to an intravenous sodium chloride load not only with exaggerated natriuresis, but also with augmented urinary cGMP excretion. The latter finding may in part be due to a greater glomerular filtration of cGMP, but increased renal contribution cannot be excluded. Apart from the possible stronger intrarenal effect of ANP on cGMP production in patients with hypertension, independent direct effect of volume expansion on cGMP excretion and modified activity of other cGMP generating systems may all be responsible for the higher urinary cGMP excretion in essential hypertension.


A psychosocial approach to dentistry for the underserved: incorporating theory into practice.
Dentistry for the underserved is more than an egalitarian social issue--it is a key factor in the health and social progress of our nation. The first signs or manifestations of several diseases such as varicella (i.e., chicken pox and shingles), STDs, and influenza become apparent in the oral cavity. The value of access to quality dentistry is an immeasurable factor in maintaining general medical health of people and fulfilling their psychosocial needs of pain reduction and enhanced cosmetics. In the United States, for the most part, only the middle and upper classes receive non-extraction, restorative, and prosthetic dentistry that is economically within their ability to pay. In addition, uninsured and poverty-level individuals often must face overwhelming long waiting lists, unnecessary referrals, lack of choice, and bureaucratic hurdles when seeking primary dental care. Therefore, it seems pertinent to put forth the question: What are the critical values and beliefs of psychosocial theory that can underscore the practice of dentistry for underserved populations in the United States? The widely employed public health theory, the health belief model (HBM), is applied to evaluate psychosocial factors in dental care for the underserved. The HBM is used to predict and explain behavioral changes in dental health and associated belief patterns. The HBM as applied to dentistry for the underserved predicts self-perceptions of susceptibility and seriousness of dental disease, health status, cues to action, and self-efficacy. Furthermore, patients can make judgments about benefits, costs, and risks of dental treatment. A theoretical approach to dentistry employing the HBM, mediated by values and culture, can provide significant insights into patient thinking, beliefs, and perceptions. These insights can mediate access to and use of primary care dental services by underserved populations. Evidence-based practice (i.e., based on research using the scientific method) has been put forth as the future of modern dentistry. However, the practice of dentistry need not just be evidence-based, but have its roots clearly grounded in theory.


Frequency and enterotoxigenicity of Campylobacter jejuni and C. coli in domestic animals in Pakistan as compared to Sweden.
Domestic and wild animals have been considered to be the most common reservoirs of Campylobacter for human infections. This study has been conducted to establish the frequency and enterotoxigenicity of C. jejuni and C. coli in the stools of domestic animals in a developing versus a developed country. Faecal samples of 300 chickens and laying hens, 102 horses, 180 cows, 92 goats and sheep were collected from Pakistan and Sweden. The hippurate hydrolysis test and CHO-cell test were performed for species differentiation and enterotoxigenicity determination respectively. The pattern and sequence of frequency distribution of Campylobacter in animals in Pakistan and Sweden were similar, the main difference being a significantly higher frequency in Pakistani samples. C. jejuni was the dominant species from both countries and Pakistani strains were more enterotoxigenic than Swedish strains. We conclude that the spread of Campylobacter infection in developing countries originates from different sources in the neighbourhood, for example animals, and unless hygienic conditions improve no change can be expected.


A rare case of follicular thyroid carcinoma in a patient with thyrotropin-secreting pituitary adenoma.
To report a rare case of a thyrotropin (TSH)-secreting pituitary adenoma associated with thyroid carcinoma. We report the clinical history, imaging studies, and laboratory and pathologic data in a male patient affected by TSH-secreting pituitary adenoma and goiter; histologic evaluation revealed thyroid carcinoma. A 50-year-old man complained of years of palpitations, hypertensive crisis, and excessive nervousness that tended to progressively worsen. The basal and dynamic hematologic evaluation showed the presence of high free thyroid hormone levels with inappropriate levels of TSH. The thyroid morphologic study using Doppler ultrasonography showed a gland of increased volume with multiple nodular lesions bilaterally. The nuclear magnetic resonance of the pituitary gland described a microadenoma. A total thyroidectomy was performed followed by neurosurgical treatment of the pituitary lesion. The definitive thyroid histologic examination showed the presence of minimally invasive follicular carcinoma of 17 mm diameter. The patient firmly refused surgical removal of the pituitary adenoma. He was started on replacement therapy with thyroxine. Twelve months later, the hematologic examinations showed normal thyroid hormone levels and a TSH of 6.97 uIU/mL. The pituitary nuclear magnetic resonance showed a stable lesion without difference in size. The clinical association between thyroid carcinoma and TSH-producing adenoma is rare, with the removal of the pituitary lesion being mandatory. Pituitary surgery, in this case, is impossible, showing that TSH-producing microadenoma could seldom have an indolent behavior.


Celiac artery compression syndrome.
Celiac artery compression syndrome is a rare disorder characterized by episodic abdominal pain and weight loss. It is the result of external compression of celiac artery by the median arcuate ligament. We present a case of celiac artery compression syndrome in a 57-year-old male with severe postprandial abdominal pain and 30-pound weight loss. The patient eventually responded well to surgical division of the median arcuate ligament by laparoscopy.


Occupational risk of the acquired immunodeficiency syndrome among health care workers.
In August 1983, we initiated nationwide prospective surveillance of health care workers with documented parenteral or mucous-membrane exposures to blood or other body fluids of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related illnesses. The purpose of the surveillance project is to quantitate prospectively the risk to health care workers of acquiring the AIDS virus, human T-cell lymphotropic virus Type III/lymphadenopathy-associated virus (HTLV-III/LAV), as a result of occupational exposures. By December 31, 1985, 938 health care workers were being followed in the surveillance project. The mean length of follow-up was 15 months (range, 0 to 56) and 531 health care workers (57 percent) had been followed for more than one year. Needlestick injuries and cuts with sharp instruments accounted for 76 percent of the exposures. Over 85 percent of all exposures were to blood or serum. None of the health care workers have acquired signs or symptoms of AIDS. Analyses of T-lymphocyte subsets were performed for 341 (36 percent) of the exposed health care workers, and tests for antibody to HTLV-III/LAV were performed for 451 (48 percent). Seven health care workers who had low helper/suppressor T-lymphocyte ratios on initial testing were retested; only three had persistently low ratios. Only two health care workers tested were seropositive for antibody to HTLV-III/LAV. The results of this surveillance project, thus far, suggest that the risk to health care workers of occupational transmission of HTLV-III/LAV is low (the upper bound of the 95 percent confidence interval for the seroprevalence rate among workers with greater than or equal to 3 months of follow-up with HTLV-III/LAV antibody testing is 1.65 percent) and appears to be related to parenteral exposure to blood.


Gamma-radiation induced changes in the physical and chemical properties of lignocellulose.
gamma-radiation induced effects on the physical and chemical properties of natural lignocellulose (jute) polymer were investigated. Samples were irradiated to required total doses at a particular dose rate. The changes in the parameters such as the tensile strength, elongation at break, and work done at rupture for the lignocellulose samples on irradiation with the gamma-rays from a cobalt-60 source were measured. The mechanical properties were found to have nonlinear relations with the radiation doses. The chemical stability of irradiated fibers was found to degrade progressively with the increase of radiation dose. Additionally, other chemical changes of the samples due to exposure to high-energy radiation were also investigated using fluorescence and infrared spectroscopic analysis. Differential scanning calorimetry and thermogravimetric studies showed a significant reduction in thermal stability. The wide-angle X-ray diffraction study showed that structural changes of cellulose appeared due to the radiation-induced chemical reaction of lignocellulose.


A new pan-nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.
The Amplatzer ventricular septal defect (VSD) occluder has a fixed stainless steel pin bottom protruding out of the surface at the center of the discs on both sides. Theoretically, this protruding bottom may interfere with epithelialization or, in some cases, cause thrombosis. To evaluate a new type of pan-nitinol VSD occluder without the protruding stainless steel pin bottom on both sides in a canine VSD model designed to ensure safety, effectiveness, and feasibility. VSDs were successfully created by transseptal ventricular septal puncture with a Brockenbrough needle and dilation with an 8-mm-diameter balloon via the right jugular vein in 9 out of 12 canines. The new type VSD occluder was successfully implanted in 8 of the 9 modeled canines. No procedure- or device-related complication was observed. Transthoracic echocardiography and MRI 2 months after device implantations showed that there was no device dislocation or heart valve dysfunction in 6 of the 8 tested canines. In addition, gross and pathological examinations 3-6 months after implantation showed no corrosion of the devices or serious inflammatory reactions in the modeled animals. Complete endothelialization was seen over the surface of the discs. The new pan-nitinol VSD device can be successfully implanted in a canine VSD model via a transcatheter approach featuring high success rate, low risk of procedure-related complications, and sound biocompatibility. The result suggests that this new VSD occluder could be used safely in future clinical trials for further test.


Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations.
Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural precursors manifested a phenotype that faithfully replicated the molecular and biochemical changes found in patient post-mortem brain tissue. We confirmed the same loss of mtDNA and complex I in dopaminergic neurons generated from the same stem cells. POLG-driven mitochondrial dysfunction led to neuronal ROS overproduction and increased cellular senescence. Loss of complex I was associated with disturbed NAD+ metabolism with increased UCP2 expression and reduced phosphorylated SirT1. In cells with compound heterozygous POLG mutations, we also found activated mitophagy via the BNIP3 pathway. Our studies are the first that show it is possible to recapitulate the neuronal molecular and biochemical defects associated with POLG mutation in a human stem cell model. Further, our data provide insight into how mitochondrial dysfunction and mtDNA alterations influence cellular fate determining processes.


Overfeeding Extends the Period of Annual Cyclicity but Increases the Risk of Early Embryonic Death in Shetland Pony Mares.
Obesity has been associated with altered reproductive activity in mares, and may negatively affect fertility. To examine the influence of long-term high-energy (HE) feeding on fertility, Shetland pony mares were fed a diet containing 200% of net energy (NE) requirements during a three-year study. The incidence of hemorrhagic anovulatory follicles (HAF) and annual duration of cyclicity were compared to those in control mares receiving a maintenance diet. Day-7 embryos were flushed and transferred between donor and recipient mares from both groups; the resulting conceptuses were collected 21 days after transfer to assess conceptus development. HE mares became obese, and embryos recovered from HE mares were more likely to succumb to early embryonic death. The period of annual cyclicity was extended in HE compared to control mares in all years. The incidence of HAFs did not consistently differ between HE and control mares. No differences in embryo morphometric parameters were apparent. In conclusion, consuming a HE diet extended the duration of cyclicity, and appeared to increase the likelihood of embryos undergoing early embryonic death following embryo transfer.


French registry of acute leukemia and myelodysplastic syndromes. Age distribution and hemogram analysis of the 4496 cases recorded during 1982-1983 and classified according to FAB criteria. Groupe Francais de Morphologie Hematologique.
During 1982 and 1983, 4496 new cases were recorded in the French Registry of acute leukemia and myelodysplastic syndromes by the French Group of Hematologic Morphology. This cooperative group associated members of 37 university centers spread throughout France; these centers handle the overwhelming majority of acute leukemias diagnoses. The cases were all classified according to FAB guidelines. Two thousand four hundred ninety-nine cases of acute myeloid leukemia were recorded, with similar total recruitment and distribution by cytologic subclass for both years. Hemogram data analysis revealed significant differences between different classes for certain parameters, particularly leukocytosis. A greater proportion of the acute myelogenous leukemias (AMLs) secondary to chemotherapy and/or radiotherapy (n = 145) were unclassifiable according to the French-American-British (FAB) system than the de novo AMLs (n = 1954). Eight hundred twenty cases of myelodysplastic syndromes were analyzed. Their frequency was underestimated due to optional reporting during the first year and the less favorable position of the university centers for recruiting these syndromes. The characteristics of the hemograms were established for acquired idiopathic sideroblastic anemia (n = 107), refractory anemia with excess blasts (RAEB) (n = 329), chronic myelomonocytic leukemia (n = 129) and RAEB in transformation (n = 65). Analysis of the 1177 acute lymphoblastic leukemias (ALLs) recorded showed good stability from one year to the next in terms of numbers of cases and distribution in the subclasses L1, L2, and L3. The distribution among these three subclasses by age also was determined. For L1 and L2 the hemogram data were examined separately for adults and children. The study of 74 cases of type L3 ALL enabled us to detail the hematologic presentation of this rare form of leukemia.


Methylation of the EcoRI recognition site does not alter DNA conformation: the crystal structure of d(CGCGAm6ATTCGCG) at 2.0-A resolution.
Methylation of nucleic acid bases is known to prevent the cleavage of DNA by restriction endonucleases. The effect on the conformation of the DNA molecule itself and hence its interactions with other DNA binding proteins has been a subject of general interest. To help address this question, we have solved the crystal structure at 2.0 A of the methylated dodecamer, d(CGCGAm6ATTCGCG), which contains the EcoRI recognition sequence and have compared the conformation of the methylated molecule with that of its nonmethylated counterpart. This methylation produces a bulky hydrophobic patch on the floor of the major groove of B-DNA which plays an important role in the mechanism of inhibition of EcoRI restriction activity. However, with the exception of small perturbations in the immediate vicinity of the methyl groups, the structure is virtually unchanged. Given the lack of a conformational change upon methylation, we have extended this thesis of the recognition process to other types of restriction systems and found that different restriction enzymes seem to have their own characteristic protein-DNA interactions. The relative spatial orientations of methylation sites and cleavage sites must play a major role in ordering protein secondary structure elements as well as subunit-subunit interactions along the DNA strand.


Evaluation of outcomes of intravenous to oral antimicrobial conversion initiatives: a literature review.
Inappropriate use of antimicrobial agents could result in antimicrobial resistance that could impact clinical cure outcomes (by increasing morbidity in terms of increased adverse events and risk of secondary and hospital-acquired infections and mortality) and increase costs to health care institutions. Thus, appropriate antimicrobial use has become vital for balancing patient safety and costs and is therefore a focus for health care institutions. This is often achieved through efforts of antimicrobial stewardship programs that include intravenous to oral conversion initiatives with clinical pharmacists playing an instrumental role in their development and implementation with medical staff approval. However, the delivery and effectiveness of these programs are quite variable. Therefore, for guiding the successful delivery and evaluations of these programs in the future, the objective of this literature review is to document the impact of intravenous to oral conversion programs in terms of clinical and economic outcomes at various institutions worldwide along with the pharmacist's role in these programs.


Does frequent eating out cause undesirable food choices? Association of food away from home with food consumption frequencies and obesity among Korean housewives.
This study examined the relationship among socioeconomic factors, frequency of food away from home (FAFH) and food-consumption patterns of 1,070 housewives, and the association of those factors with obesity, using data from the third Korea National Health and Nutrition Examination Survey. Although lower intakes of fruits, meats, and fast foods were associated with seldom eating out, no consistent pattern was observed regarding the relationship between the frequency of FAFH and food consumption for all groups of housewives. Further analysis indicated that obesity rates were lower among housewives aged 20-49 years with 7-12 years of education and moderate eating-out frequency, compared to older, less educated women. It appeared that reducing the frequency of FAFH does not always entail desirable food intakes among full-time housewives in Korea. Our findings suggest that choosing healthy meals away from home is more important for housewives than refraining from eating out.