A Case of Persistent Generalized Retrograde Autobiographical Amnesia Subsequent to the Great East Japan Earthquake in 2011.
Functional retrograde autobiographical amnesia is often associated with physical and/or psychological trauma. On 11 March 2011, the largest earthquake on record in Japan took place, and subsequent huge tsunami devastated the Pacific coast of northern Japan. This case report describes a patient suffering from retrograde episodic-autobiographical amnesia for whole life, persisting for even more than five years after the disaster. A Japanese man, presumably in his 40s, got police protection in April 2016 but was unable to respond to question about his own name. He lost all information about his personal identity, and his memory was wholly lost until the disaster on 11 March 2011. He was able to recall his life after the disaster, and semantic memories and social abilities were largely preserved. A medical examination performed on 1 November 2016 verified that he was awake, alert, and oriented to time, place, and person (except for himself). General physical and neurological examinations revealed no pathological findings. He also experienced some symptoms associated with posttraumatic stress disorder (PTSD), such as intrusive thoughts, flashbacks, and nightmares. No abnormalities were detected by biochemical test and brain magnetic resonance imaging (MRI). Physicians and other professionals who take care of victims of disaster should be aware of dissociative spectrum disorders, such as psychogenic amnesia.


Bactericidal effect of 5-azacytidine on Escherichia coli carrying EcoRII restriction-modification enzymes.
5-Azacytidine was found to be bactericidal to Escherichia coli carrying plasmids specifying EcoRII restriction-modification systems, but not to the same strains lacking these plasmids. Of other base analogs tested, only 5(beta-D-ribofuranosyl)isocytidine had similar, although weaker, effects. Plasmids that had lost the EcoRII restriction-modification system did not confer sensitivity to 5-azacytidine. Mutants defective in the restriction function remained sensitive to the toxic effects of the drug; however, a mutant defective in the modification function lost most of the sensitivity to 5-azacytidine. For the bactericidal effect to be seen, the cells had to be growing; cells in the stationary phase of growth were not killed by the drug. The drug inhibited the methylase enzyme, and an inhibitor of the enzyme could be detected in vitro in extracts of cells that had been treated with 5-azacytidine. This nalidixic acid inhibited its formation. Coumermycin but not nalidixic acid antagonized the bactericidal effect of the drug; however, coumermycin was more effective in preventing the inhibition of the methylase by 5-azacytidine than was nalidixic acid.


Clinical equipoise: actual or hypothetical disagreement?
In his influential 1987 essay, "Equipoise and The Ethics of Randomized Clinical Research," Benjamin Freedman argued that Charles Fried's theoretical equipoise requirement threatened clinical research because it was overwhelmingly fragile and rendered unethical too many randomized clinical trials. Freedman, therefore, proposed an alternative requirement, the clinical equipoise requirement, which is now considered to be the fundamental or guiding principle concerning the ethics of enrolling patients in randomized clinical trials. In this essay I argue that Freedman's clinical equipoise requirement is ambiguous and can be interpreted in (at least) two different ways. I furthermore claim that, ironically, the best interpretation of the clinical equipoise requirement opens Freedman to the same objection that he leveled against Fried twenty-five years ago; namely, that it (Freedman's clinical equipoise requirement) renders unethical too many randomized clinical trials.


Functional Analysis of Amorpha-4,11-Diene Synthase (ADS) Homologs from Non-Artemisinin-Producing Artemisia Species: The Discovery of Novel Koidzumiol and (+)-α-Bisabolol Synthases.
The production of artemisinin, the most effective antimalarial compound, is limited to Artemisia annua. Enzymes involved in artemisinin biosynthesis include amorpha-4,11-diene synthase (ADS), amorpha-4,11-diene 12-monooxygenase (CYP71AV1) and artemisinic aldehyde Δ(11)13 reductase (DBR2). Although artemisinin and its specific intermediates are not detected in other Artemisia species, we reported previously that CYP71AV1 and DBR2 homologs were expressed in some non-artemisinin-producing Artemisia plants. These homologous enzymes showed similar functions to their counterparts in A. annua and can convert fed intermediates into the following products along the artemisinin biosynthesis in planta These findings suggested a partial artemisinin-producing ability in those species. In this study, we examined genes highly homologous to ADS, the first committed gene in the pathway, in 13 Artemisia species. We detected ADS homologs in A. absinthium, A. kurramensis and A. maritima. We analyzed the enzymatic functions of all of the ADS homologs after obtaining their cDNA. We found that the ADS homolog from A. absinthium exhibited novel activity in the cyclization of farnesyl pyrophosphate (FPP) to koidzumiol, a rare natural sesquiterpenoid. Those from A. kurramensis and A. maritima showed similar, but novel, activities in the cyclization of FPP to (+)-α-bisabolol. The unique functions of the novel sesquiterpene synthases highly homologous to ADS found in this study could provide insight into the molecular basis of the exceptional artemisinin-producing ability in A. annua.


Testing can enhance episodic memory updating in younger and older adults.
Older adults sometimes show impaired memory for recent episodes, especially those that are similar but not identical to existing memories. Two experiments examined if interpolated testing between episodes improves recent memories for older and younger adults (N = 60 per group and experiment). Participants studied two lists of cue-response word pairs. Some pairs included the same cue in both lists with changed responses. Between lists, List 1 pairs were tested (Experiments 1 and 2), tested with corrective feedback (Experiment 1 only), or restudied (Experiment 2 only). On a final cued recall test, participants attempted to recall the List 2 response, indicated if responses had changed between lists, and if so, attempted to recall the List 1 response. List 2 recalls for changed pairs operationalized episodic memory updating. Older adults showed poorer List 2 recall than younger adults. But both age groups showed improved List 2 recall following interpolated testing with or without feedback compared to no-test and restudy contrast conditions. This so-called forward testing effect was accompanied by improved memory for responses having changed across lists. These results contrast with the inhibitory deficit proposal that older adults should be more interference prone than younger adults when competing responses are more accessible during encoding. These findings are more compatible with the view that retrieval practice of competing responses can support the encoding of cross-episode associations and potentially mitigate interference, thus improving age-related associative memory deficits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


MLN4924 neddylation inhibitor promotes cell death in paclitaxel-resistant human lung adenocarcinoma cells.
Acquired resistance to first-line chemotherapeutics, including paclitaxel (PTX), is a primary factor contributing to chemotherapy failure in non-small cell lung cancer (NSCLC) patients. Previous studies have identified that targeting NEDD8-activating enzyme (NAE) with MLN4924 effectively overcomes platinum resistance in preclinical models of ovarian cancer. However, the underlying mechanisms are yet to be fully elucidated. The present study demonstrates that the inhibition of the neddylation pathway with MLN4924 an NAE inhibitor inhibited protein neddylation, inactivated cullin-RING E3 ligase and exhibited a potent antiproliferative effect on PTX-resistant A549 and H460 cells (A549/PTX and H460/PTX). The application of MLN4924 promotes apoptosis and DNA damage in A549/PTX and H460/PTX cells. Additionally, MLN4924 abrogated the 3-dimensional growth potential of these cells and inhibited the formation of the A549/PTX and H460/PTX spheroids. Notably, combining MLN4924 with PTX did not exhibit synergy in PTX-resistant NSCLC cells. Taken together, the results of the current study suggest that MLN4924 may be utilized as an effective strategy for the treatment of PTX-resistant NSCLC.


Right ventricular hypoplasia: outcome after conservative perinatal management.
Isolated right ventricular hypoplasia is a rare congenital cardiac anomaly. A case described in which prenatal diagnosis was made by echocardiography. Conservative perinatal management produced a favourable short-term outcome without compromising the definitive surgical intervention later. The decisions were based on principles used in the treatment of pulmonary atresia with intact interventricular septum.


Human chorionic gonadotropin and luteinizing hormone-releasing hormone reverse the blockade of ovulation in pregnant mare's serum gonadotropin-primed immature rats by the anti-androgenic drug, hydroxyflutamide.
The present study was designed to examine mechanism(s) of the anti-ovulatory action of the anti-androgen, hydroxyflutamide (OH-F). Prepubertal rats were treated with 4 IU pregnant mare's serum gonadotropin (PMSG) (day -2) to induce first estrus and ovulation. They received OH-F in sesame oil or oil alone at 08:00 and 20:00 h on day 0 (the day of proestrus) and ovulations were assessed on the morning of day 1. Eighty-three percent of control animals ovulated with a mean of 7.7 +/- 1.1 corpora lutea per rat. Hydroxyflutamide blocked ovulation in all but 2 of the 12 rats receiving this drug alone. All of OH-F treated rats that received 5 and 25 IU human chorionic gonadotropin (hCG) ovulated with means +/- SEM of 9.1 +/- 0.1 and 7.3 +/- 1.4 corpora lutea per rat, respectively. The dose of 0.2 IU hCG was essentially ineffective, while the effect of 1.0 IU hCG was intermediate. At the dose of 20 ng and above (100 and 500 ng) luteining hormone-releasing hormone (LHRH) completely overcame the ovulation blockade in the OH-F treated animals, while a 4-ng dose was ineffective. At 18:00 h on the day of proestrus, serum LH levels in control animals were 17.56 +/- 2.60 ng/mL, which were 920% above basal levels (1.90 +/- 0.13) indicating a spontaneous LH surge. This surge was suppressed in OH-F treated rats. Injection of LHRH, at the dose of 20 ng and above, reinstated the LH release in OH-F treated animals. Thus, the anti-androgen, OH-F, inhibits ovulation in PMSG-treated immature rats through its interference with the preovulatory LH surge; the inhibition can be reversed by hCG or LHRH. Hydroxyflutamide does not appear to interfere at the level of the pituitary, but may have direct action at the hypothalamic and (or) extrahypothalamic sites involved in the generation of positive feedback signals that control LH release.


Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas.
Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, representing 90% of all oral carcinomas and accounting for 3-5% of all malignancies. The WWOX gene (WW-domain containing oxidoreductase) is a candidate tumor suppressor gene located at 16q23.3-24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we demonstrated an altered WWOX gene in 50% (10/20) of OSCCs. Using nested RT-PCR, mRNA transcription was altered in 35% of the tumors, with the complete absence of transcripts in 2 samples as well as absence of exons 6-8 (2 tumors), exon 7 (1 tumor), exon 7 and exon 6-8 (1 tumor) and partial loss of exons 8 and 9 (1 tumor). To determine if the aberrant transcripts were translated, Western blots were performed in all samples; however, only the normal protein was detected. By immunohistochemistry, a reduction in Wwox protein expression was observed, affecting 40% of the tumors when compared with normal mucosa. In addition, a novel somatic mutation (S329F) was found. The presence of alterations in mRNA transcription correlated with the reduced expression of Wwox protein in the tumors. These results show that the WWOX gene is frequently altered in OSCC and may contribute to the carcinogenesis processes in oral cancer.


Identification of upstream stimulatory factor binding sites in the human IGFBP3 promoter and potential implication of adjacent single-nucleotide polymorphisms and responsiveness to insulin.
The actions of IGFs are regulated at various levels. One mechanism involves binding to IGF-binding protein-3 (IGFBP-3) for transport, thus governing bioavailability. IGFBP3 transcription is modulated by many hormones and agents that stimulate or inhibit growth. We have previously shown in pediatric and adult cohorts a correlation between IGFBP-3 serum levels and two single-nucleotide polymorphisms (SNPs) located within the minimal promoter (-202 A/C and -185 C/T). Functionality of these SNPs was further explored in hepatic adenocarcinoma-derived SK-HEP-1 cells using transient transfections of luciferase constructs driven by different haplotypes of the IGFBP3 promoter. Basal luciferase activity revealed a significant haplotype-dependent transcriptional activity (at nucleotides -202 and -185, AC > CC, P < 0.001; AC > CT, P < 0.001; AC > AT, P < 0.001). Insulin treatment produced a similar haplotype dependence of luciferase activity (AC > CC, P = 0.002; AC > CT, P < 0.001; AC > AT, P = 0.011). However, induction ratios (insulin/control) for CC and AT were significantly higher compared with AC and CT (CC > AC, P = 0.03; CC > CT, P = 0.03; AT > AC, P = 0.03; AT > CT, P = 0.04). Gel retardation assays were used to identify upstream stimulatory factor (USF-1 and USF-2) methylation-dependent binding to E-box motifs located between the SNPs. Mutation of the USF binding site resulted in a significant loss of insulin stimulation of luciferase activity in the transfection assay. Chromatin immunoprecipitation with anti-USF-1/-2 showed an enrichment of IGFBP3 promoter in insulin-treated cells compared with unstimulated cells. Bisulfite sequencing of genomic DNA revealed that CpG methylation in the region of USF binding was haplotype dependent. In summary, we report a methylation-dependent USF binding site influencing the basal and insulin-stimulated transcriptional activity of the IGFBP3 promoter.


Regulation of the lateral association of phospholipase Cbeta2 and G protein subunits by lipid rafts.
One function of membrane domains of liquid-ordered lipids or "rafts" may be to stabilize complexes of signaling proteins, thereby playing a role in the transduction of cellular signals. Here, we have used fluorescence methods to directly test this idea by assessing the ability of phospholipase Cbeta2 (PLCbeta2) to associate with G protein subunits on model membranes in the fluid phase and on membranes that contain domains of lipids in the liquid-ordered phase (rafts). We find that the apparent dissociation constant for the equilibrium between PLCbeta2 and Galpha(q)(GTPgammaS) was identical on both types of membrane surfaces. However, the degree of association between PLCbeta2 and Gbetagamma subunits was significantly reduced on the surfaces containing rafts. Time studies indicate that this phenomenon is a dynamic process. Incorporating the lipid substrate of PLCbeta2 into membranes that forms rafts, we find that its basal activity is unaffected. However, its activation by Gbetagamma subunits is inhibited, supporting a reduced degree of interaction between these two proteins when rafts are present. Since lipid rafts affected PLCbeta2-Gbetagamma association and not PLCbeta2-Galpha(q)(GTPgammaS) association, we explored the possibility that the membrane interaction of Gbetagamma differed when rafts are present. We find that although the membrane partition coefficient of Gbetagamma is not significantly changed in the presence of rafts, proteolysis of Gbetagamma by trypsin increases and the ability of Gbetagamma Tyr/Trp fluorescence to be quenched by iodide ions decreases when rafts are present. These results suggest a model in which lipid rafts occlude the PLCbeta2 interaction site on Gbetagamma subunits by localizing these subunits at the domain interface.


Implication of European-derived adiposity loci in African Americans.
Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively). We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.


Leptospira interrogans in Rodents from Cape Verde.
Leptospirosis is an important worldwide zoonotic disease that can infect both animals and humans. In most cases, leptospirosis is a nonspecific self-limiting illness, but some patients can develop a severe form with a high mortality. This study was carried out in Santiago Island, Cape Verde, in 2012-2013. A total of 62 wild rodents (Rattus rattus and Mus domesticus) were analyzed. The lipL32 gene, present only in pathogenic Leptospira spp., was amplified by PCR, and 16 samples were positive (25.8%). In both rodent species, Leptospira interrogans was identified. The results show the presence of pathogenic Leptospira in the three localities analyzed in Santiago. The presence of L. interrogans demonstrates a serious health risk for the population, since this species has been associated with the most severe form of leptospirosis, the Weil's disease in humans, a severe infection with jaundice, renal failure, and hemorrhage.


Expression of interferon regulatory factor 5 is regulated by the Sp1 transcription factor.
The transcription factor, interferon regulatory factor 5 (IRF5), is important in the induction of type I interferon, proinflammatory cytokines and chemokines, and is involved in autoimmune diseases and tumourigenesis. However, the mechanisms underlying the transcriptional regulation of wild‑type IRF5 remain to be fully elucidated. The present study was primarily designed to clarify whether specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially, the IRF5 promoter region was cloned and its promoter activity was examined using Hela and HEK 293 cells. Deletion analyses revealed that the region spanning ‑179 to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this region contained three putative Sp1 binding sites, and mutational analyses revealed that all the Sp1 sites contributed to transcriptional activity. Secondly, the overexpression of Sp1 was found to increase the activity of the IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays and polymerase chain reaction analysis, respectively. By contrast, treatment with mithramycin and Sp1 small interfering RNA significantly reduced the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an electrophoretic mobility shift assay and a chromatin immunoprecipitation assay demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo. These results suggested that the Sp1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.


[The immune-enhancing effects of oral administration of strains bifidobacteria in experiments].
This paper reviews evidence for the immune-enhancing effects of probiotics. The influence of bifidobacteria B. lactis 668 and B. lactis BB12 on the immune functions and the structure of peripheral lymphoid organs in male Wistar rats was investigated after 3 weeks feeding. Rats were oral administrated with bifidobacteria x 10(7) CFU/sm3. The rats of control group had no feeding any probiotics. This is evidence that probiotic bacteria improve host immune function: cell-mediated and humoral immunity in rats. The increased activity of peritoneal macrophages was confirmed by enhancement superoxid anion pro duction that leads to improving unspecific resistance of organism. The immunostimulatory effects of probiotics was also confirmed by morphological investigation of peripheral lymphoid organs.


Assembly of Multifold Helical Polyoxometalate-Based Metal-Organic Frameworks as Anode Materials in Lithium-Ion Batteries.
For exploring the multifold helical fabrication of polyoxometalate (POM)-based hybrid compounds, four POM-based crystalline compounds with different meso-helices, H3[Ag27(trz)16(H2O)6][SiW12O40]2·5H2O (1), H[Ag27(trz)16(H2O)4][PW12O40]2·2H2O (2), [Ag23(trz)14(H2O)2][HSiW12O40] (3), and [Ag23(trz)14(H2O)2][PW12O40] (4), were successfully isolated by using the delicate 1,2,3-triazole ligand and silver ions in this work. Crystal analysis reveals that compounds 1 and 2 and compounds 3 and 4 are isomorphous and display 2-/4-fold mixed meso-helices and simple 2-fold meso-helices, respectively. In addition, due to the reversible multielectron redox behavior and electron storage functions of POMs, compounds 1 and 3 were studied as anode materials in lithium-ion batteries (LIBs). Compounds 1 and 3 show very high lithiation capacities (1356 and 1140 mAh g-1, respectively) in the initial cycle, which are much higher than those of (NBu4)4[SiW12O40] and commercial graphite at the current density of 100 mA g-1. More importantly, both compounds also show good stable performance after 100 cycles.


Neuroblastoma in Africa: A Survey by the Franco-African Pediatric Oncology Group.
Neuroblastoma is a sympathoadrenal lineage neural crest-derived tumor. It is the third most common childhood malignancy in the Western world. Studies from the United States show that black patients with neuroblastoma have a greater proportion of high-risk neuroblastoma with poorer prognosis compared with white patients. In Africa, there are few published data on the epidemiology and management of neuroblastoma. The primary aim of this study was to assess the diagnostic and therapeutic resources available for the management of neuroblastoma within the Franco-African Pediatric Oncology Group (GFAOP). A survey was conducted in the pediatric oncology centers of the GFAOP. Participating GFAOP centers were Abidjan, Algiers, Bamako, Dakar, Lubumbashi, Lomé, Ouagadougou, Rabat, Tananarive Antananarivo, and Tunis. Questionnaires were sent out by e-mail to the principal investigators at each participating GFAOP center in December 2013. Ten (62%) of 16 GFAOP centers responded to the questionnaire. Neuroblastoma represented only 3% to 5% of childhood cancers in the sub-Saharan African centers, with the exception of Antananarivo, where it represented 7.5%. In contrast, in the northern African centers of Tunis, Rabat, and Algiers, neuroblastoma accounted for 30%,10%, and 7% of childhood cancer, respectively. At initial diagnosis, 50% to 80% of patients had metastatic neuroblastoma in eight of 10 centers. Based on this survey, neuroblastoma seems to be less common in sub-Saharan Africa. The proportion of patients with metastatic neuroblastoma seems to be higher than reported in Western countries.


The Correlation Between Liver Fat Content and Ulcerative Colitis Disease Severity.
To evaluate the association between disease severity and hepatic steatosis in patients with ulcerative colitis (UC) and non-alcoholic steatohepatitis (NASH). Consecutively selected UC patients admitted to the gastroenterology clinic were enrolled in the study. UC severity was assessed by Truelove and Witts classification. Patients with severe UC were excluded from the study. NASH was determined based on persistently elevated serum aminotransferase levels and detection of fatty liver ultrasound. Patients with other etiologies for elevated aminotransferase levels were excluded. Liver fat content (LFC) was assessed by measuring liver fat score (LFS). One hundred patients (42% male) were included in the study. According to liver ultrasound examination, 62 (%) patients were identified with grade 1 fatty liver disease, and 38 (%) patients were classified as advanced (grade 2 and 3) fatty liver disease. Sixty-one patients had left-sided UC and (46%) had mild UC disease severity index. LFS was significantly higher in UC patients with the moderate disease than patients with mild disease (3.53±2.68 vs. 5.89±2.85, respectively; P<0.01). Nevertheless, no significant difference was observed in LFS regarding UC extension. There was no significant difference between NASH ultrasound grades in view of UC severity and extension. LFC might be associated with UC severity.


Efficacy of granulocyte-macrophage colony-stimulating factor on the survival of ischaemic skin flaps in rats.
Our objective was to find out whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the survival of skin flaps in rats. Random skin flaps were raised in 30 male Sprague-Dawley rats, and recombinant GM-CSF 50 microg in 0.5 ml saline solution (n=15) or 0.5 ml saline solution alone (n=15) was injected intradermally into the area of the flap after it had been raised. Surviving areas were measured after seven days, and the median area surviving in the group treated with GM-CSF was greater than that in the control group (728 mm2 (range 565-1120) compared with 985 mm2 (range 636-1368), p=0.005). These results suggest that in this model, GM-CSF given postoperatively improves the viability of ischaemic skin flaps.


Gram-negative prosthetic joint infections managed according to a multidisciplinary standardized approach: risk factors for failure and outcome with and without fluoroquinolones.
To describe the outcome and risk factors for treatment failure of 76 Gram-negative bacilli (GNB) prosthetic joint infections (PJIs) managed with a curative intent according to a standardized protocol derived from published guidelines. We analysed data from all the cases of GNB-PJI treated surgically over an 8 year period. Treatment failure was defined as persistence or recurrence of PJI signs during follow-up, resulting in additional surgery and/or antibiotic administration or death. Treatment failure within the follow-up period (median = 2.6 years) was observed in 16 of 76 (21.1%) patients. The failure rate was similar whether the patients were treated with fluoroquinolones in the whole cohort (22.4% versus 16.7%, P = 0.75) and after stratification according to the surgical procedure. The low failure rate observed in patients not receiving fluoroquinolones might be explained by the standardized attitude of maintaining intravenous β-lactams throughout treatment duration (median = 90 days). In multivariate analysis, C-reactive protein level ≥175 mg/L was significantly associated with treatment failure (adjusted HR = 7.75, 95% CI = 2.66-22.59, P < 0.0001). Management according to standardized procedures may improve the prognosis of GNB-PJI. Intravenous β-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones.


Beyond the silence: bilateral somatosensory stimulation enhances skilled movement quality and neural density in intact behaving rats.
It is thought that a close dialogue between the primary motor (M1) and somatosensory (S1) cortices is necessary for skilled motor learning. The extent of the relative S1 contribution in producing skilled reaching movements, however, is still unclear. Here we used anodal transcranial direct current stimulation (tDCS), which is able to alter polarity-specific excitability in the S1, to facilitate skilled movement in intact behaving rats. We hypothesized that the critical role of S1 in reaching performance can be enhanced by bilateral tDCS. Pretrained rats were assigned to control or stimulation conditions: (1) UnAno: the unilateral application of an anodal current to the side contralateral to the paw preferred for reaching; (2) BiAno1: bilateral anodal current; (3) BiAno2: a bilateral anodal current with additional 30ms of 65μA pulses every 5s. Rats received tDCS (65μA; 10min/rat) to the S1 during skilled reach training for 20 days (online-effect phase). After-effect assessment occurred for the next ten days in the absence of electrical stimulation. Quantitative and qualitative analyses of online-effects of tDCS showed that UnAno and BiAno1 somatosensory stimulation significantly improve skilled reaching performance. Bilateral BiAno1 stimulation was associated with greater qualitative functional improvement than unilateral UnAno stimulation. tDCS-induced improvements were not observed in the after-effects phase. Quantitative cytoarchitectonic analysis revealed that somatosensory tDCS bilaterally increases cortical neural density. The findings emphasize the central role of bilateral somatosensory feedback in skill acquisition through modulation of cortico-motor excitability.


Prevalence of lower airway diseases in patients with chronic rhinosinusitis.
There is high prevalence of lower airway diseases in patients with chronic rhinosinusitis and frequently co-existing lower airway diseases have not been diagnosed before. To examine the prevalence of lower airway diseases in patients with chronic rhinosinusitis. Seventy-three consecutive patients with chronic rhinosinusitis were enrolled in this prospective study. With routine physical examination, spirometry and methacholine bronchial provocation test were performed and chest simple radiograph or chest computed tomography was taken. Thirty patients (41.1%) had lower airway diseases. There were 8 patients with asthma, 5 with asymptomatic bronchial hyperresponsiveness, 11 with small airway disease, 2 with chronic obstructive pulmonary disease and 4 with bronchiectasis. Of these 30 patients, 21 patients (70.0%) were first diagnosed as having lower airway diseases in this study.


Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.
Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.


Novel and nontraditional use of stable isotope tracers to study metal bioavailability from natural particles.
We devised a novel tracing approach that involves enriching test organisms with a stable metal isotope of low natural abundance prior to characterizing metal bioavailability from natural inorganic particles. In addition to circumventing uncertainties associated with labeling natural particles and distinguishing background metals, the proposed "reverse labeling" technique overcomes many drawbacks inherent to using radioisotope tracers. Specifically, we chronically exposed freshwater snails ( Lymnaea stagnalis ) to synthetic water spiked with Cu that was 99.4% (65)Cu to increase the relative abundance of (65)Cu in the snail's tissues from ~32% to >80%. The isotopically enriched snails were then exposed to benthic algae mixed with Cu-bearing Fe-Al particles collected from the Animas River (Colorado), an acid mine drainage impacted river. We used (63)Cu to trace Cu uptake from the natural particles and inferred their bioavailability from calculation of Cu assimilation into tissues. Cu assimilation from these particles was 44%, indicating that 44% of the particulate Cu was absorbed by the invertebrate. This demonstrates that inorganic particulate Cu can be bioavailable. The reverse labeling approach shows great potential in various scientific areas such as environmental contamination and nutrition for addressing questions involving uptake of an element that naturally has multiple isotopes.


Planning Today for Tomorrow's Research: Analysis of Factors Influencing Participation in a Pediatric Cancer Research Biorepository.
Biobanks have become a powerful tool that fosters biomedical research. The success of biobanks depends upon people's perception and willingness to donate their samples for research. This is the first biorepository in Egypt, hence, little is known about the beliefs and attitudes of parents toward participation. To investigate the level of willingness of Egyptians to donate samples of their children and themselves for research and the different factors influencing participation. A structured questionnaire was designed covering multiple items expected to affect the enrollment decision. This was conducted in-person, and data collected included demographic data, socioeconomic, and educational level. In addition, in the case of refusal, participants were asked about reasons behind their decision. Only about 3.1% of patients have not been enrolled in the project, and 0.3% have withdrawn. Three demographic factors were found having disparate trends in the decision-making process to participate or not: father's education (p = 0.0001), mother's education (p = 0.0001), and father's age (p = 0.034). Egyptian parents were willing to donate their samples as well as their children's samples in our research biorepository. The idea of participation was presented in an interview during which the consent form was explained in a comprehensive transparent way allowing participants the right to refuse or withdraw at any time. Still, different communication approaches are needed with older, more highly educated parents to encourage them to participate.


COVID-19 Experiences Predicting High Anxiety and Depression Among a Sample of BRCA1/BRCA2-positive Women in the US.
Purpose. During the COVID-19 pandemic, breast and ovarian cancer survivors experienced more anxiety and depression than before the pandemic. Studies have not investigated the similarities of this trend among BRCA1/2 -positive women who are considered high risk for these cancers. The current study examines the impact of COVID-19 experiences on anxiety and depression in a sample of BRCA1/2 -positive women in the U.S. Methods. 211 BRCA1/2 -positive women from medically underserved backgrounds completed an online survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for associations between COVID-19 experiences and self-reported anxiety and depression stratified by demographic factors. Results. Overall, women who reported quarantining/isolation (aOR, 0.46, 95% CI, 0.24-0.88) experienced significantly fewer depressive symptoms than women who did not report this experience. Racial/ethnic minority women caring for someone at home during COVID-19 were 3.78 times more likely (95% CI, 1.04-13.6) to report high anxiety while non-Hispanic white women were less likely (aOR, 0.36, 95% CI, 0.10-1.33, p -interaction=0.011). Conclusions . To date, this is the first study to analyze anxiety and depression considering several COVID-19 predictors among BRCA1/2 -positive women. Our findings can be used to inform future research and advise COVID-19-related mental health resources specific to these women.


Postnatal growth preceding sudden infant death syndrome.
To compare postnatal growth preceding the sudden infant death syndrome (SIDS) with that of age matched controls. Retrospective case-control study. Each SIDS victim was matched with two controls on date of parental interview, postnatal age, and neighborhood. Clinical and demographic data were collected by parental interview and by review of medical records, and interval body weights were obtained from health visitors' records. All infants dying of SIDS between 1 May, 1987 and 30 April, 1989 in a geographically defined region consisting of four health districts in Avon and North Somerset in southwest England. Seventy-eight of the 99 SIDS victims and 139 of 156 control infants were included in the final analysis. There was no significant difference between SIDS victims and the controls in either of the two indices of postnatal growth which were analyzed. The mean growth rates (+/- 1 SEM) between birth and the last live weight (age equivalent weight for control infants) were 27.1 +/- 1.0 g/day for the SIDS cases and 28.3 +/- 1.5 g/day for the control infants. The mean growth rate (+/- 1 SEM) between the last two live weights were 31.5 +/- 2.9 and 24.9 +/- 2.1 g/day for the SIDS and control infants, respectively. Stratification of the infants by sex, gestational age, maternal smoking during pregnancy, breast versus bottle feeding, or age at death, did not result in any significant differences between SIDS and controls in either of the indices of postnatal growth rate. The 20 SIDS cases which were excluded from the final analysis did not differ from 78 whose data was analyzed, with regard to established SIDS risk factors, age at death, or postmortem weight. No difference was found between the postnatal growth of SIDS victims and that of age matched control infants.


Virus-stimulated neutrophils in the tumor microenvironment enhance T cell-mediated anti-tumor immunity.
The tumor microenvironment (TME) fosters tumors by attenuating anti-tumor immunity, reinforcing tumor cell survival and increasing angiogenesis. Among the constituents of the TME, here, we focused on tumor-associated neutrophils (TANs). First, we found that the combination of poly I:C and inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) synergistically suppressed tumor growth in the B16-F10 melanoma mouse model. In this model, poly I:C contributed to the recruitment of CD11b+Ly6G+ neutrophils to the TME, and co-injection of poly I:C and HVJ-E increased CD11b+Ly6G+FAS+ TAN in the TME. Depletion of neutrophils abolished the synergistic anti-tumor effect of HVJ-E and poly I:C in B16-F10 tumors. We revealed that C-X-C motif chemokine ligand 2 (CXCL2) is produced in the TME by poly I:C, but HVJ-E enhanced neutrophil infiltration of the TME does not occur. An anti-CXCL2 antibody inhibited the tumor suppression by HVJ-E+poly I:C. HVJ-E in combination with recombinant CXCL2 protein or CXCL2 pDNA suppressed mouse melanoma by increasing cytotoxic T lymphocyte activity against B16-F10 melanoma, which was abolished by an anti-Ly6G antibody. HVJ-E directly and indirectly increased FAS and ICAM-1 expression in cultured bone marrow-derived naïve neutrophils. Thus, HVJ-E activates anti-tumor immunity via anti-tumorigenic neutrophils in the TME. An HVJ-E vector containing the CXCL2 gene may be applicable as a novel cancer gene therapy strategy.


Mineralization pathways of organic matter deposited in a river-lake transition of the Rhone River Delta, Lake Geneva.
During the éLEMO endeavour (a research project in which the Russian MIR submersibles were used for studying Lake Geneva) four sediment cores were retrieved on a transect from the delta of the Rhone River towards the profundal part of the lake. The degradation pathways of organic material (OM) were investigated considering different electron acceptors. Essentially, OM at the delta sites had a higher fraction of terrestrial material than the lake sites indicated by higher C/N ratios, and higher long-chain n-alkane and alcohol concentrations. The concentrations of chlorins were higher at the distant sites indicating more easily degradable OM in the sediments. However, the chlorin index that was used to determine the degradation state of the OM material indicated that pigment derived OM of deltaic sediments was less degraded than that of the profundal sediments. The fluxes of reduced species from the sediments decreased from the delta to the profundal for CH4 (from 2.3 to 0.5 mmol m(-2) d(-1)) and NH4(+) (from 0.31 to 0.13 mmol m(-2) d(-1)). Fluxes of Fe(ii) and Mn(ii), however, increased although they were generally very low (between 9 × 10(-5) and 7.6 × 10(-3) mmol m(-2) d(-1)). Oxygen concentration profiles in the pore waters revealed lower fluxes close to the river inflow with 4.3 and 4.1 mmol m(-2) d(-1) compared to two times higher fluxes at the profundal sites (8.8 and 8.2 mmol m(-2) d(-1)). The rates for totally mineralized OM (Rtotal) at the shallower sites (4.7 mmol C m(-2) d(-1)) were only half of those of the deeper sites (9.7 mmol C m(-2) d(-1)). Accordingly, not only the rates but also the mineralization pathways differed between the shallow and profundal sites. Whereas only 0-6% of the OM was mineralized aerobically at the shallow sites (since almost all O2 was used to oxidize the large flux of CH4 from below) the situation was reversed at the deeper sites and the fraction of aerobically degraded OM was 72-78%. We found a better efficiency in CH4 production per carbon equivalent deposited at the deeper sites as a result of the higher degradability of the mainly autochthonous OM in spite of the lower deposition rate and the higher degradation state of the OM compared to the delta sites.


Experimental studies and numerical analysis of the inflation and interaction of vascular balloon catheter-stent systems.
Balloon angioplasty with stenting is a well-established interventional procedure to treat stenotic arteries. Despite recent advances such as drug eluting stents, clinical studies suggest that stent design is linked to vascular injury. Additionally, dilation of the medical devices may trigger pathological responses such as growth and migration of vascular smooth cells, and may be a potent stimulus for neointimal hyperplasia. The purpose of this study is to experimentally investigate the mechanical characteristics of the transient expansion of six commercially available balloon-expandable stent systems, and to develop a robust finite element model based on the obtained experimental results. To reproduce the inflation of stent systems as in clinical practice, a pneumatic-hydraulic experimental setup is built, able to record loads and deformations. Characteristic pressure-diameter diagrams for the balloon-expandable stents and the detached balloons are experimentally obtained. Additionally, typical measures such as the burst opening pressure, the maximum dog-boning and foreshortening, and the elastic recoil are determined. The adopted constitutive models account for elastoplastic deformation of the stent, and for the nonlinear and anisotropic behavior of the balloon. The employed contact algorithm, based on a C(2)-continuous surface parametrization, efficiently simulates the interaction of the balloon and stent. The computational model is able to successfully capture the experimentally observed deformation mechanisms. Overall, the numerical results are in satisfactory agreement with experimental data.


Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons.
During neuronal migration in the developing brain, it is thought that the centrosome precedes the nucleus and provides a cue for nuclear migration along the microtubules. In time-lapse imaging studies of radially migrating granule cells in mouse cerebellar slices, we observed that the movements of the nucleus and centrosome appeared to occur independently of each other. The nucleus often migrated ahead of the centrosome during its saltatory movement, negating the supposed role of the centrosome in pulling the nucleus. The nucleus was associated with dynamic microtubules enveloping the entire nucleus and stable microtubules extending from the leading process to the anterior part of the nucleus. Neither of these perinuclear microtubules converged at the centrosome. Disruption or excess formation of stable microtubules attenuated nuclear migration, indicating that the configuration of stable microtubules is crucial for nuclear migration. The inhibition of LIS1 function, a regulator of a microtubule motor dynein, specifically blocks nuclear migration without affecting the coupling of the centrosome and microtubules in the leading process, suggesting that movements of the nucleus and centrosome are differentially regulated by dynein motor function. Thus, the nucleus moves along the microtubules independently of the position of the centrosome in migrating neurons.


[Three-dimensional finite element analysis of two different framework designs of compound galvano-ceramic bridges].
To analyze stress distribution of two framework designs in compound galvano-ceramic bridges made with three-dimensional finite element models. Three-dimensional finite element models were developed for compound galvano-ceramic bridges with two designed retainers of Ni-Cr frameworks which ringed or partially covered the electroformed gold caps. The models were vertically loaded 200 N on the center of the occlusal surface of the pontic and loaded 400 N on the center of buccoclusal marginal ridge from buccal aspect to lingual aspect at a 30 degree angle with the occlusion plane respectively. The stress distributions and the level of stress concentration in the two models were analyzed by the FEA software. Stress distributing in two designed framework of compound galvano-ceramic bridges were similar. The highest von Mises stress of compound galvano-ceramic bridges was concentrated in the distal connector of the pontic and retainer. Under the vertical loading, the von Mises stress was 24.17 MPa for the partial cover retainer of the Ni-Cr framework and 24.85 MPa for the circular retainer. Under the lateral loading, the corresponding figures were 42.83 MPa and 42.69 MPa. No matter vertical or lateral loading, the margin of electroformed cap was the concentration area of the von Miese stress. In this study, the stress concentration area of compound galvano-ceramic bridges with Ni-Cr framework and electroformed gold caps was the connector and the margin of electroformed cap was the insubstantial area.


Subclavian artery aneurysm associated with absence of the ipsilateral internal carotid artery.
A 48-year-old male presented with a rare subclavian artery aneurysm associated with absence of the ipsilateral internal carotid artery. The aneurysm was resected and replaced with a Gore Tex artificial graft. Computed tomography, angiography and cerebral blood flow findings suggest that defect of the right internal carotid artery occurred in the developmental stage. There was no past history of trauma, nor histological evidence of inflammatory or sclerotic changes in the aneurysmal wall. The two vascular lesions may have been influenced by a synchronous causative factor in his developmental stage.


A systems approach to ethical problems.
Codes of professional ethics and cases designed to teach ethical decision making are written for individual professionals and ignore the systems level of analysis. They typically employ a lineal view of causality and overvalue placement of blame as a component of ethical problem solving. This article takes a systems approach to ethical problems and identifies aspects of systems that promote or impede ethical decision making. Psychological abuse of children is used as an example of a problem requiring a coordinated, systemic response to ethical issues such as autonomy, privacy, and confidentiality.


Inflammatory breast cancer: A review from our experience.
Inflammatory Breast Cancer (IBC) is a distinct and rare type of breast cancer accounting for up to 6% of all breast cancer cases in Europe. The aim of this study was to investigate diagnostic methods, treatments, and outcome after IBC in patients treated at a single institution in Denmark. All patients treated for IBC at Aarhus University Hospital between 2000 and 2014 were identified and included in the cohort. Survival was assessed using Kaplan-Meier curves and log-rank statistics. A total of 89 patients were identified with a median follow up of 3.6 years. The overall survival at 5 and 10 years were 41% and 18%, respectively. The disease free survival at 5 and 10 years were 47% and 27%, respectively. Thirty-four percent had distant metastasis at time of diagnosis. Patients with ER positive tumors had a significantly better overall survival than patients with ER negative tumors (p = 0.01). Despite a more aggressive systemic and loco-regional treatment today, IBC is still a very serious disease with a high mortality.


Artificial intelligence: a computerized decision aid for trauma.
A computerized decision support system has been developed to advise ATLS-trained surgeons on the initial definitive management of patients with penetrating injuries of the abdomen immediately following resuscitation and stabilization. The program was developed as an "expert system," using the techniques of artificial intelligence. It is able to suggest: the need for further examination; additional tests; diagnoses; and treatments. In this study, the advice offered by the expert system was compared to that of physicians-in-training. Five actual patient care situations were presented to the system and to 13 medical students and surgical residents: four MS-III, three PGY-I, three PGY-III, and three PGY-V. The suggestions of each of the 13 trainees, the advice of the expert system, and the actual management were blinded. Five surgeons versed in trauma and otherwise not involved in the project judged whether each of the 15 purported management plans was acceptable and ranked them in order of preference. Only the actual care and the advice from the system were judged acceptable for all five problems. The rankings of the expert system were better than those of any individual trainee. The differences were statistically significant for two of the three chief residents, five of nine residents overall, and all four students. This preliminary validation of a prototype expert system is encouraging for the prospect of a computerized decision support system that can help surgeons make initial definitive management plans for patients with major trauma.


Hemoglobin-Based Oxygen Carrier (HBOC) Development in Trauma: Previous Regulatory Challenges, Lessons Learned, and a Path Forward.
Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist ® (BAXTER), Hemopure ® (BIOPURE) and PolyHeme ® (NORTHFIELD) for resuscitating hypotensive shock. These trials all failed due to safety concerns (e.g., cardiac events, mortality) and certain protocol design limitations. In 2008 the Food and Drug Administration (FDA) put all HBOC trials in the US on clinical hold due to the unfavorable benefit:risk profile demonstrated by various HBOCs in different clinical studies in a meta-analysis published by Natanson et al. (2008). During standard resuscitation in trauma, organ dysfunction and failure can occur due to ischemia in critical tissues, which can be detected by the degree of lactic acidosis. SANGART'S Phase 2 trauma program with MP4OX therefore added lactate >5 mmol/L as an inclusion criterion to enroll patients who had lost sufficient blood to cause a tissue oxygen debt. This was key to the successful conduct of their Phase 2 program (ex-US, from 2009 to 2012) to evaluate MP4OX as an adjunct to standard fluid resuscitation and transfusion of RBCs. In 2013, SANGART shared their Phase 2b results with the FDA, and succeeded in getting the FDA to agree that a planned Phase 2c higher dose comparison study of MP4OX in trauma could include clinical sites in the US. Unfortunately, SANGART failed to secure new funding and was forced to terminate development and operations in Dec 2013, even though a regulatory path forward with FDA approval to proceed in trauma had been achieved.


Down-regulation of Kelch domain-containing F-box protein in Arabidopsis enhances the production of (poly)phenols and tolerance to ultraviolet radiation.
Phenylpropanoid biosynthesis in plants engenders myriad phenolics with diverse biological functions. Phenylalanine ammonia-lyase (PAL) is the first committed enzyme in the pathway, directing primary metabolic flux into a phenylpropanoid branch. Previously, we demonstrated that the Arabidopsis (Arabidopsis thaliana) Kelch domain-containing F-box proteins, AtKFB01, AtKFB20, and AtKFB50, function as the negative regulators controlling phenylpropanoid biosynthesis via mediating PAL's ubiquitination and subsequent degradation. Here, we reveal that Arabidopsis KFB39, a close homolog of AtKFB50, also interacts physically with PAL isozymes and modulates PAL stability and activity. Disturbing the expression of KFB39 reciprocally affects the accumulation/deposition of a set of phenylpropanoid end products, suggesting that KFB39 is an additional posttranslational regulator responsible for the turnover of PAL and negatively controlling phenylpropanoid biosynthesis. Furthermore, we discover that exposure of Arabidopsis to ultraviolet (UV)-B radiation suppresses the expression of all four KFB genes while inducing the transcription of PAL isogenes; these data suggest that Arabidopsis consolidates both transcriptional and posttranslational regulation mechanisms to maximize its responses to UV light stress. Simultaneous down-regulation of all four identified KFBs significantly enhances the production of (poly)phenols and the plant's tolerance to UV irradiation. This study offers a biotechnological approach for engineering the production of useful phenolic chemicals and for increasing a plant's resistance to environmental stress.


Obesity and its effects on the esophageal mucosal barrier.
Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.


The relationship of drug use to suicide ideation and attempts among African American, Hispanic, and white non-Hispanic male adolescents.
This study presents self-report cross-sectional and longitudinal data on associations between drug use, suicide ideation, and attempts in a multiethnic sample of seventh- and eighth-grade male adolescents attending school in the greater Miami, Florida, area. African Americans had the highest prevalence of 6-month ideation (20.5%), and Haitians had the highest attempts (11.4%). For the total sample, tranquilizers had the highest odds ratio for ideation (3.4), and PCP for attempts (6.2). Psychoactive drug-use was consistently related to attempts among Hispanics, white non-Hispanics, and African Americans. Acculturation strains interacted with cocaine and crack to predict suicide attempts among Hispanic respondents.


Study of liver differentiation in vitro.
A clonal rat fetal liver cell line that expresses the functions of differentiated liver cells under controllable conditions has been established. Normal fetal liver cells were transformed by a temperature-sensitive A (tsA) mutant (tsA209) of simian virus 40. At the permissive temperature (33 degrees C), the tsA209-transformed liver cell line (RLA209-15) can be cultured indefinitely and cloned readily. The RLA209-15 cells were temperature sensitive for maintenance of the transformed phenotype. These transformed liver cells selectively lost four characteristics of the transformed phenotype at the restrictive temperature (40 degrees C): generation time of the cells increased, the saturation density decreased, the efficiency of growth on nontransformed cell layers decreased, and the ability to clone in soft agar was lost. The transformation can be reversed simply by a shift in temperature. RLA209-15 fetal liver cells synthesized alpha-fetoprotein albumin, and transferrin. At 33 degrees C, the levels of these liver proteins were relatively low. At 40 degrees C the transformed phenotype was lost and the levels of alpha-fetoprotein, albumin, and transferrin were greatly increased. At the restrictive temperature, maximal induction of the synthesis of alpha-fetoprotein, albumin, and transferrin was achieved 3-4 d after the upward shift in temperature. The synthesis of alpha-fetoprotein then decreased; the synthesis of albumin and transferrin, however, was maintained. A second phase of albumin and transferrin synthesis was observed in all cultures after 6 d or more at 40 degrees C. Alpha-Fetoprotein, albumin, and transferrin secreted by RLA209-15 cells were immunologically indistinguishable from authentic alpha-fetoprotein, albumin, and transferrin, respectively. RLA209-15 cells, like primary cultures of hepatocytes and a simian virus 40 tsA255-transformed fetal liver cell line (RLA255-4) reported earlier from this laboratory, responded to glucagon with markedly elevated levels of cyclic AMP. Thus, it appears that glucagon receptors characteristic of hepatocytes are retained in the simian virus 40 tsA-transformed fetal liver cells.


Blueprint for design: creating models that direct change.
The need for healthcare system change is overwhelming: broken systems, an inadequate workforce, patient safety failures, and lack of access to healthcare are but a few of the significant problems confronting healthcare today. Most people agree that things need to change, but they are not sure on what to change or how to change them. A well-developed model can serve as the currency for that change. By considering the evidence of what has worked well in the past and marrying that with what the future will require, we can create a strong sustainable model for professional practice. The authors explore that evidence and discuss the structure, process, and outcomes that should be considered in designing care delivery models for the future.


[Risk factors associated to upper gastrointestinal bleeding in non intensive care units].
Upper gastrointestinal bleeding--UGB-, as a complication, is well studied at intensive care units (ICU), but is less known in non ICU settings. To determine incidence and risk factors of this entity at clinical hospitalization. A case-control study of patients with gastric ulcer disease diagnosed by endoscopy who presented with melena and hematemesis. Ten controls were taken for each case, matching sex, age and prophylaxis for gastric hemorrhage. Demographic data and other know risks factors were analyzed. We found ten bleeding case among 35070 discharges (incidence: 2.8/10000 discharges). Mortality was not increased but the number of transfusion was higher in the bleeding group. We found an assocciation betwen UGB and systemic inflammatory response syndrome--SIRS-(OR: 9.22 IC 95% 2.98-28.17) and diabetes (OR: 7.8 IC 95% 2.3-26.8). The rest of the factors studied did not rich a statistical significance. UGB during clinical hospitalization is a rare complication that requires an increased staying at hospital and a great number of transfusions. It may be probably associated in a positive way with diabetes and SIRS.


Patterns and predictors of sleep pattern disturbance after cardiac surgery.
The purposes of this study were to examine changes in sleep patterns after cardiac surgery and the contributions of preoperative sleep to postoperative sleep. Seventy-two cardiac surgery patients wore wrist actigraphs for 3 days during the preoperative period (T1) and the 1st (T2), 4th (T3), and 8th (T4) postoperative weeks. They completed the Pittsburgh Sleep Quality Index at T1, T3, and T4. Sleep was most disturbed during the 1st postoperative week and improved at T3 and T4. Overall, sleep pattern disturbance was higher at T3 and T4 than at T1. Age, gender, preoperative New York Heart Association Functional Class, and preoperative sleep variables explained 20%-50% of the variance in sleep at T2, T3, and T4. Sleep disturbance is present preoperatively and continues during the postoperative period.


Trisomy 8 syndrome.
Trisomy 8 syndrome, with or without mosaicism, is characterized by the following clinical signs and symptoms: mental retardation, deformed skull, prominent forehad, high-arched palate, low-set and/or dysplastic ears, long and slender trunk, reduced joint mobility, and deep plantar furrows. The deep furrow or longitudinal crease of the sole may be pathognomonic for the syndrome. It should be noted that it has been seen in other rare syndromes. It is recommended that a child with mental retardation and associated multiple anomalies should be subjected to a cytogenetic study in order to define the incidence of this syndrome. Differnetial diagnosis should include: Fong's syndrome, arthrogryposis and otopalato-digital syndrome. It is interesting to note that there seem to be individuals who have had no physical abnormalities and have been identified during an evaluation for repeated abortions. The above described case of trisomy 8 mosaicism was seen and treated for many years by many different specialists without an accurate diagnosis.


TSH Variability of Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet Form.
Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min-max): 0.28 (0.1-0.45) versus 0.34 (0.01-0.78) mIU/L, p = 0.041] as compared to those taking liquid formulation [TSH (min-max): 0.28 (0.1-0.47) versus 0.30 (0.1-0.55) mIU/L, p = 0.345]. The use of L-T4 liquid formulation, as compared to that of tablets, resulted in a significantly higher number of DTC patients maintaining TSH values in range for the ATA risk score, reducing TSH variability over the time.


Neoadjuvant Treatment for Locally Invasive Esophageal Cancer.
Locally advanced esophageal carcinoma has a poor prognosis, and epidemiologic trends show that more patients are being diagnosed with locally advanced esophageal carcinoma and with adenocarcinoma histology. This prompts a review and evaluation of the field regarding standard of care treatment for patients with locally advanced esophageal carcinoma, both adenocarcinoma and squamous cell carcinoma. We review the evidence showing the moderate benefit of neoadjuvant chemoradiation followed by esophagectomy compared to perioperative chemotherapy plus esophagectomy in patients who are good operative candidates. Also, we summarize the emerging clinical trial landscape in the perioperative setting primarily seeking to apply targeted therapies against HER2 (trastuzumab or pertuzumab) or immune checkpoint inhibitors against programmed death 1 (PD-1; pembrolizumab and nivolumab) or programmed death ligand 1 (PD-L1; durvalumab). Understanding the foundations that have determined the current standard of care for patients with locally advanced esophageal carcinoma will aid in interpreting the clinical trial results that will soon appear with the novel treatment strategies.


[Phage lysis typing and epidemiology of diphtheria 1975-1984].
Phage typing of the available diphtheria strains from epidemics and isolated diphtheria infections in the Federal Republic of Germany since 1975 showed that the various waves of the disease were caused by pathogenic strains which differed from each other in lysis type and lysogenetic spectrum. The individual regional outbreaks, therefore, were not epidemiologically interlinked. Both a high incidence of diphtheria cases and isolated cases occurring in a particular region and within the same time period, however, were caused by the same pathogen with identical lysis type and lysogenetic pattern. On the other hand, the toxinogenic strains introduced from countries with a high prevalence of the disease had clearly different typing characteristics. According to our present studies on the incidence of pathogen carriers, no toxin-producing diphtheria bacteria are circulating in the indigenous population. It can be assumed, therefore, that the outbreaks of diphtheria during the last few years were caused by such imported strains. Since the importation of toxin-producing diphtheria bacteria is unavoidable and may occur at all times, universal active immunisation in childhood, as well as timely revaccination of adolescents and adults, are mandatory prophylactic measures to prevent new epidemics.


The Management of Postoperative Atrial Fibrillation (POAF): A Systematic Review.
Postoperative atrial fibrillation (POAF) refers to new-onset atrial fibrillation (AF) that develops after surgery and is associated with an increased risk of mortality and thromboembolic events. The optimal management and treatment methods for POAF complications are not yet fully established. This systematic review aimed to evaluate the various treatment and management approaches currently available in terms of their suitability, efficacy, and side effects in handling POAF incidence post-surgery. Google Scholar and PubMed electronic databases were searched extensively for relevant articles examining the various management techniques currently used to manage POAF and published between 2018 and 2023. Data were collected on the type of surgery the patients underwent, POAF definition period, intervention, and outcome of interest. Following a systematic assessment guided by the inclusion criteria, 10 of the 579 studies retrieved were included in this study, and 293,417 POAF cases were recorded. Three of these studies used different rhythm control and rate control treatments to manage POAF cases, while seven studies used various anticoagulation therapies to manage POAF incidence. For asymptomatic patients within one to three days of surgery, rate control is sufficient to manage POAF, and routine rhythm control is not needed; rhythm control should be reserved for patients who develop complications such as hemodynamic instability. Anticoagulation was performed in patients whose POAF exceeded four days after surgery. Anticoagulation was associated with an increased risk of mortality, stroke, thromboembolic events, and major bleeding in patients who underwent coronary artery bypass graft (CABG) surgery. In contrast, in a few other studies, anticoagulation treatment led to improved outcomes in patients who developed POAF. A wide range of management methods are available for POAF after different types of surgery. However, there is only limited evidence to guide the clinical practice. The data available are mainly retrospective and insufficient to accurately evaluate the efficacy of the various management methods available for POAF. Future research should make efforts to standardize the treatment for this condition.


Clinically significant delayed postsphincterotomy bleeding: a twelve year single center experience.
Bleeding following endoscopic biliary sphincterotomy (ES) is associated with morbidity. We sought to identify endoscopic findings and outcome of patients with delayed bleeding after ES. A retrospective study was carried out in a tertiary referral center. A gastrointestinal bleeding and endoscopy database was used to identify all patients with delayed post-ES bleeding from 1994 to 2006. Early endoscopic evaluation and endoscopic hemostasis was performed. Endoscopic findings, factors associated with bleeding severity, identification of stigmata of hemorrhage, and success of endoscopic treatment were identified. There were 84 patients with delayed post-ES bleeding. Bleeding was classified as mild in 31 (36.9%), moderate in 29 (34.5%), and severe in 24 (28.6%). Thirteen of these 84 (15.5%) experienced bleeding at the time of initial ES. Endoscopic findings for evaluation of bleeding included active bleeding in 50 (59.5%) and stigmata of recent bleeding in 34 (40.5%) patients. Endoscopic treatment was employed in 74 (88%) patients. Monotherapy was used in 39.2% and combined therapy was used in 60.8% patients. Recurrence of bleeding was significantly more common in the severe group (P<0.001). A multivariate analysis showed that coagulopathy was a predictive factor for severe post-ES bleeding. Active bleeding or stigmata of hemorrhage occurs in the majority of patients with clinically significant delayed post-ES bleeding. Endoscopic therapy is useful in controlling bleeding in nearly all cases, though multimodal therapy and repeat endoscopic procedures may be required. Coagulopathy is a risk factor for severe bleeding; preventive measures in these patients may reduce morbidity.


Underwater endoscopic mucosal resection of serrated adenomas.
Serrated polyps, which are considered to be precursors of colorectal carcinoma, include hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. With the exception of hyperplastic polyps, all of these lesions must be removed. This study sought to examine whether underwater endoscopic mucosal resection is a safe and effective technique for treating serrated polyps. Cases in which patients were submitted for underwater endoscopic mucosal resection and histologically diagnosed with sessile serrated adenoma were prospectively registered. The median patient age was 54.5 years (range, 48 to 72 years), and the patients included 4 men (28.5%) and 10 women (71.5%). One lesion (6.2%), 10 lesions (62.5%), 1 lesion (6.2%), 3 lesions (18.8%) and 1 lesion (6.2%) were found in the cecum, the ascending colon, the hepatic flexure, the transverse colon and the descending colon, respectively. The median lesion size was 20 mm (range, 10 to 35 mm). Eight lesions (50%) were removed en bloc, and the remaining eight lesions (50%) were removed using a piecemeal technique. None of the cases were complicated by perforation or delayed bleeding. Underwater resection could be a feasible, safe and effective alternative for the resection of sessile serrated adenomas.


Down syndrome and Alzheimer's disease: Common pathways, common goals.
In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments.


Structure of coated pits and vesicles.
Purified coated vesicles typically contain clathrin and auxiliary structural proteins of about 100 000 and 50 000 relative molecular mass (Mr). A model is described for the packing of clathrin trimers into the characteristic pentagons and hexagons of the surface lattices of coats. In a coated vesicle, clathrin appears to bind to an inner 'core' of particles containing the 100 000 and 50 000 Mr proteins. These core proteins may, in turn, bind to receptors in the membrane of the vesicle. The vesicle itself surrounds specific content molecules bound to their respective receptors. Budding coated vesicles are believed to act as molecular filters in cells. The known structural features of coated membranes are discussed in terms of this apparent role.


Vascular endothelial growth factor gene polymorphisms and serum levels in Behçet's disease.
Vascular endothelial growth factor (VEGF) is important for angiogenesis and inflammation, both of which are codependent and contribute to the pathophysiology of Behçet's disease (BD). In this report, we sought to investigate whether the selected VEGF polymorphisms [-634 C/G, +936 C/T and an 18 bp insertion/deletion (I/D) at -2549 of the VEGF promoter region] are associated with susceptibility and severity of BD in the Tunisian population. One hundred and thirty-five Tunisian BD patients and 157 healthy controls were recruited. The VEGF gene was genotyped by polymerase chain reaction followed by digestion with restriction endonucleases. VEGF serum levels of BD patients and healthy controls were measured by enzyme-linked immunosorbent assay. We found no association between the VEGF polymorphisms and the susceptibility to BD. However, when data were analysed according to the presence of each symptom, we found a positive association between VEGF 18 bp I/D polymorphism and ocular involvement as well as BD severity. Indeed, among the BD patients, the frequency of the 18 bp I/I genotype was less in patients with ocular inflammation (6.1% vs 24.6%, P = 0.007) and in patients with severe BD (9.2% vs 21.4%, P = 0.0014). Moreover, the mean serum VEGF level was considerably higher in BD patients (P < 0.01) than in healthy controls. We suggest that VEGF gene polymorphisms may be involved in the development of the ocular BD as well as the severity of the disease.


Organ uptake, toxicity and skin clearance of ruthenium contrast agents monitored in vivo by x-ray fluorescence.
Aims: To investigate the distribution and toxicity of ruthenium nanoparticles (Ru NPs) injected intravenously in mice. Methods: We synthesized Ru NPs, followed their biodistribution by x-ray fluorescence (XRF) imaging and evaluated organ toxicity by histopathology and gene expression. Results: Ru NPs accumulated, mainly in liver and spleen, where they were phagocyted by tissue macrophages, giving a transient inflammation and oxidative stress response that declined after 2 weeks. Ru NPs gradually accumulated in the skin, which was confirmed by microscopic examination of skin biopsies. Conclusion: Ru NP toxicity in recipient organs is transient. Particles are at least partially excreted by the skin, supporting a role for the skin as a nanoparticle clearing organ.


Could knee inflammatory synovitis be induced by pembrolizumab?
Pembrolizumab, a selective anti-PD-1 humanized monoclonal antibody, reactivates T cells to fight cancer. Immune-related adverse events such as autoimmune colitis, pneumonitis, hepatitis, nephritis, hypophysitis, and thyroiditis may occur during, or weeks to months after therapy. Pemprolizumab-induced synovitis is rarely reported. With the wide use of immunotherapy to treat cancers, physicians need to be aware of this rare immune-related adverse event and provide immediate treatment to avoid permanent joint damage.


Ileocaecal tuberculosis.
This report is of a single case of ileocaecal tuberculosis presenting as subacute bowel obstruction, with clinical features suggesting an inflammatory cause. The diagnosis of tuberculosis was made at operation although tuberculosis was suspected beforehand. Treatment consisted of triple therapy only and appeared to be successful in so far as loss of symptoms resulted.


Compressed sensing of twisted photons.
The ability to completely characterize the state of a system is an essential element for the emerging quantum technologies. Here, we present a compressed-sensing-inspired method to ascertain any rank-deficient qudit state, which we experimentally encode in photonic orbital angular momentum. We efficiently reconstruct these qudit states from a few scans with an intensified CCD camera. Since it only requires a small number of intensity measurements, our technique provides an easy and accurate way to identify quantum sources, channels, and systems.


Bullet emboli to the pulmonary artery: a rare occurrence.
In two cases of bullet embolization to the pulmonary artery the bullets were left in place. Removal of the bullet was felt to be an unnecessary surgical risk. A two-year and six-year follow-up revealed no complications. In both instances the patients received adequate blood replacement for resuscitation and levels of antibiotics considered high enough to eradicate any possible infection from the contaminated missile.


Innovative technologies to manage aflatoxins in foods and feeds and the profitability of application - A review.
Aflatoxins are mainly produced by certain strains of Aspergillus flavus, which are found in diverse agricultural crops. In many lower-income countries, aflatoxins pose serious public health issues since the occurrence of these toxins can be considerably common and even extreme. Aflatoxins can negatively affect health of livestock and poultry due to contaminated feeds. Additionally, they significantly limit the development of international trade as a result of strict regulation in high-value markets. Due to their high stability, aflatoxins are not only a problem during cropping, but also during storage, transport, processing, and handling steps. Consequently, innovative evidence-based technologies are urgently required to minimize aflatoxin exposure. Thus far, biological control has been developed as the most innovative potential technology of controlling aflatoxin contamination in crops, which uses competitive exclusion of toxigenic strains by non-toxigenic ones. This technology is commercially applied in groundnuts maize, cottonseed, and pistachios during pre-harvest stages. Some other effective technologies such as irradiation, ozone fumigation, chemical and biological control agents, and improved packaging materials can also minimize post-harvest aflatoxins contamination in agricultural products. However, integrated adoption of these pre- and post-harvest technologies is still required for sustainable solutions to reduce aflatoxins contamination, which enhances food security, alleviates malnutrition, and strengthens economic sustainability.


Subjective evaluation of uncorrected vision in patients undergoing cataract surgery with (diffractive) multifocal lenses and monovision.
To analyze patient satisfaction and difficulties with bilateral multifocal intraocular lenses (IOLs) implantation and aspheric monofocal IOLs implantation using monovision, after cataract surgery. A total of 61 participants were included in the study, 29 with monovision and 32 with multifocal lenses. The inclusion criteria were patients undergoing phacoemulsification for bilateral visual impairment due to cataracts and presenting with postoperative visual acuity of 20/30 or better for distance and line J3 or better for near vision. The 2 groups had similar results regarding difficulties with daily activities such as distance vision, near vision, watching television, reading, cooking, using a computer or cellphone, shaving/putting on makeup and shopping. There were differences in responses between the groups regarding difficulty with night vision (P=0.0565) and night driving (P=0.0291). Degree of satisfaction in terms of distance vision without glasses was statistically significantly better in monovision group (P=0.0332), but not for near (P=0.9101). Both techniques yielded satisfactory results regarding visual acuity for different activities without the need to use glasses. Multifocal lenses are a good option for patients with the exception of night driving, and who desire independence from glasses.


Dopamine Inhibition Differentially Controls Excitability of Substantia Nigra Dopamine Neuron Subpopulations through T-Type Calcium Channels.
While there is growing appreciation for diversity among ventral tegmental area dopamine neurons, much less is known regarding functional heterogeneity among the substantia nigra pars compacta (SNc) neurons. Here, we show that calbindin-positive dorsal tier and calbindin-negative ventral tier SNc dopaminergic neurons in mice comprise functionally distinct subpopulations distinguished by their dendritic calcium signaling, rebound excitation, and physiological responses to dopamine D2-receptor (D2) autoinhibition. While dopamine is known to inhibit action potential backpropagation, our experiments revealed an unexpected enhancement of excitatory responses and dendritic calcium signals in the presence of D2-receptor inhibition. Specifically, dopamine inhibition and direct hyperpolarization enabled the generation of low-threshold depolarizations that occurred in an all-or-none or graded manner, due to recruitment of T-type calcium channels. Interestingly, these effects occurred selectively in calbindin-negative dopaminergic neurons within the SNc. Thus, calbindin-positive and calbindin-negative SNc neurons differ substantially in their calcium channel composition and efficacy of excitatory inputs in the presence of dopamine inhibition.SIGNIFICANCE STATEMENT Substantia nigra dopaminergic neurons can be divided into two populations: the calbindin-negative ventral tier, which is vulnerable to neurodegeneration in Parkinson's disease, and the calbindin-positive dorsal tier, which is relatively resilient. Although tonic firing is similar in these subpopulations, we find that their responses to dopamine-mediated inhibition are strikingly different. During inhibition, calbindin-negative neurons exhibit increased sensitivity to excitatory inputs, which can then trigger large dendritic calcium transients due to strong expression of T-type calcium channels. Therefore, SNc neurons differ substantially in their calcium channel composition, which may contribute to their differential vulnerability. Furthermore, T-currents increase excitation efficacy onto calbindin-negative cells during dopamine inhibition, suggesting that shared inputs are differentially processed in subpopulations resulting in distinct downstream dopamine signals.


Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.
The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus, intra-abdominal fat showed a unique set of relationships to metabolic parameters which could be further related to certain environmental variables.


Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with dyslipidemia.
Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our previous pooled data analysis of the genome scans for low HDL-C and FCHL, which identified three shared chromosomal regions for a qualitative HDL-C trait on 8q23.1, 16q23.3, and 20q13.32. This study further investigates these regions as well as two other loci we identified earlier for premature CHD on 2q31 and Xq24 and a locus for high serum triglycerides (TGs) on 10q11. We analyzed 67 microsatellite markers in an extended study sample of 1,109 individuals from 92 low HDL-C or FCHL families using both qualitative and quantitative lipid phenotypes. These analyses provided evidence for linkage (a logarithm of odds score of 3.2) on 10q11 using a quantitative HDL-C trait. Importantly, this region, previously linked to TGs, body mass index, and obesity, provided evidence for association for quantitative TGs (P = 0.0006) and for a combined trait of HDL-C and TGs (P = 0.008) with marker D10S546. Suggestive evidence for linkage also emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL-C and TGs.


Bronchiolitis obliterans in bone marrow transplantation and its relationship to chronic graft-v-host disease and low serum IgG.
The records of 549 bone marrow transplant (BMT) patients at The Johns Hopkins Oncology Center during a 9-year period were reviewed to determine the incidence of bronchiolitis obliterans (BrOb). Seven patients had BrOb. All seven died, and BrOb was a contributing cause of death in six patients. Only recipients of allogeneic BMT were at risk for developing BrOb (2% incidence). Three cases were incidentally discovered at autopsy in patients who died less than 120 days after BMT from ventilatory failure owing to interstitial pneumonitis. Four cases were patients who died greater than 120 days after BMT. Of this latter group, all had overt chronic graft-v-host disease (CGVHD). Among 120 day survivors of allogeneic BMT, 6% of those with CGVHD developed BrOb as compared with none of those without CGVHD (P = .008). Five percent of patients with reduced IgG levels at day 120 developed BrOb as compared with none of those with normal IgG (P = .04). The incidence of BrOb in 120-day survivors was 14% (4 of 29) in patients with both CGVHD and decreased serum IgG, whereas patients with CGVHD only (0 of 25), those with decreased IgG levels only (0 of 53), and those with no CGVHD and normal IgG levels (0 of 70) did not develop BrOb.


A simple medium without blood modified for successful isolation & cultivation of LD bodies.
A simple growth medium for primary isolation and subsequent cultivation of Leishmania donovani promastigotes without using whole blood is described. This medium is modified from Aljeboori's biphasic medium (used originally only for cultivation), containing only beef extract, peptone, sodium chloride, bactoagar and foetal calf serum (FCS). We have modified the medium by adding glucose and ascertaining the pH in the solid phase and by drastically reducing (91%) FCS in the liquid phase. The medium helps in isolation of L. donovani promastigotes from kala-azar patients, in addition to luxurious growth of parasites. The medium is simple, reliable, reproducible and convenient, with minimal interference in using the parasitic cells for immunological, molecular and isoenzyme studies.


Low-power-penalty wavelength multicasting for 36 Gbit/s 16-QAM coherent optical signals in a silicon waveguide.
All-optical wavelength multicasting has been experimentally demonstrated for 36 Gbit/s 16-quadrature amplitude modulation signals based on four-wave mixing processes in a silicon waveguide with multiple pumps. In our experiment, dual pumps are injected together with the signal into the waveguide and nine idlers are generated, involving five wavelength multicasting channels. Coherent detection and advanced digital signal processing are employed, and the recovered constellation diagrams of the multicasting idlers show a root-mean-square error vector magnitude degradation as small as 2.74%. The bit error rate (BER) results are measured for these multicasting idlers, and the power penalties are all lower than 0.96 dB at the BER of 3.8×10(-3) (corresponding to the forward error correction threshold).


Assessing the Nutritional-Value-Based Therapeutic Potentials and Non-Destructive Approaches for Mulberry Fruit Assessment: An Overview.
Among different fruits, mulberry is the most highlighted natural gift in its superior nutritional and bioactive composition, indispensable for continuing a healthy life. It also acts as a hepatoprotective immunostimulator and improves vision, anti-microbial, anti-cancer agent, anti-stress activity, atherosclerosis, neuroprotective functions, and anti-obesity action. The mulberry fruits also help reduce neurological disorders and mental illness. The main reason for that is the therapeutic potentials present in the nutritional components of the mulberry fruit. The available methods for assessing mulberry fruits are mainly chromatographic based, which are destructive and possess many limitations. However, recently some non-invasive techniques, including chlorophyll fluorescence, image processing, and hyperspectral imaging, were employed to detect various mulberry fruit attributes. The present review attempts to collect and explore available information regarding the nutritional and medicinal importance of mulberry fruit. Besides, non-destructive methods established for the fruit are also elaborated. This work helps encourage many more research works to dug out more hidden information about the essential nutrition of mulberry that can be helpful to resolve many mental-illness-related issues.


[Toxicity of hydroxyapatite nanoparticles on rabbits].
To study the toxicity of nano-hydroxyapatite on rabbits by vein. The hydroxyapatite solution was intravenous injected into 50 New Zealand white rabbits with different concentration, then to observe the reactions and the survial rates of rabbits, and to investigate the effects of nano-HA to the liver function, renal function, enzyme and Ca, Mg, P. The medium lethal dosege of nano-HA administrated intravenous (iv) was determined as 200mg/kg. The level of phosphorous increased but calcium and magnesium kept stable. LDH, CPK, GOP and GDT dramatically increased in 30 minutes after injection, arriving the peak at 2 hours later, however, they all returned to normal 24h after injection. BUN and ALP got to the peak at 24 hours later, then decreased rapidly to normal level. The other indexes almost maintained at normal level. Nano-hydroxyapatite has no accumulative toxicity to rabbits, it is suggested that it is safe when the hydroxyapatite-sol was applied intravenously as a drug carrier in small dosage more less than the medium lethal dose, even as a kind of anticancer drug.


[A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer].
We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.


Central venous catheters in pediatric patients--subclavian venous approach as the first choice.
It is critical to establish a safe and functional i.v. access in severely sick patients. We evaluated the frequency of application and complications of central venous catheters in a pediatric intensive care unit. Pediatric patients in whom central venous catheters were inserted between March 1997 and May 1999 in the Pediatric Emergency Room and Intensive Care Unit were enrolled in this study. Patients were evaluated with respect to age, sex, weight, central venous catheter indication, site, duration of catheter stay and complications. During the study period a total of 156 central venous catheters were successfully inserted into 146 patients. Of the 156 central venous catheter attempts, 148 (94.9%) were placed into the subclavian vein, six were inserted into the femoral vein, and two into the jugular vein. In 156 attempts, arterial injuries occurred in 20 cases (12.8%). Pneumothorax developed in two patients on mechanical ventilation. Three catheters had to be removed due to catheter related infections. The mortality rate was 0%. We concluded that subclavian central venous catheterization is a safe procedure with minimal complications in pediatric patients. Arterial injury was the most frequent complication. In experienced hands, the success rate was 100%. Subclavian central venous catheter insertion may be considered as the first approach in critically ill patients.