Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity.
Macrophages were isolated from the strongly immunogenic, non-metastasizing FS6 sarcoma transplanted in syngeneic C57BL/6 mice and from a weakly immunogenic, spontaneously metastasizing line (mFS6) of the same tumor. Macrophages isolated from the FS6 sarcoma non-specifically inhibited growth and DNA synthesis of tumor cells in vitro. After culture FS6 macrophages rapidly lost their cytotoxic activity and became capable of non-specifically stimulating tumor growth in vitro. Macrophages obtained from the mFS6 tumor non-specifically enhanced the proliferative activity of tumor target cells and this capacity was maintained when the macrophages were cultured.


Accommodation and the third spatial harmonic.
Mathews and Kruger recently reported that accommodative tracking of sine wave grating targets is best between 1 and 7 cpd. Their study suggests that the spatial third harmonic might not enhance the accommodative response if the fundamental is higher than roughly 2 cpd. This study tested the effect of adding the third harmonic with targets that included 1, 3, and 5 cpd fundamental sine wave gratings, compound gratings with the third harmonic of each of these fundamentals added in either peaks-add or peaks-subtract phase, as well as each third harmonic presented alone at one-third of the contrast of the fundamental gratings. Accommodation was monitored continuously with a dynamic infrared optometer while the subject viewed the gratings in a Badal stimulus system. Dioptric vergence changed sinusoidally over a 2.00 or 0.50 D range at 0.2 Hz. A Fast Fourier Transform extracted the amplitude and phase of each response at the temporal frequency of the stimulus. The third harmonic enhanced the accommodative response only when the fundamental was 1 cpd. This was true at both amplitudes of target motion. This contradicts models that suggest that high spatial frequencies are used to refine the accommodative response. Second, the responses to the peaks-add and peaks-subtract phase conditions were essentially the same for each fundamental. This suggests that the effect of harmonics cannot be described by any simple linear relationship between the increased luminance gradient of the grating target and the accommodative response. Third, the accommodative response to gratings with a 5 cpd fundamental were smaller than the responses to gratings with the 3 cpd fundamental. This contradicts the gradient hypothesis of accommodative control inasmuch as the luminance gradient is steeper in the gratings with the 5 cpd fundamental. Alternatively, it seems that harmonics will enhance an accommodative response regardless of phase if they are effective accommodative stimuli on their own.


The association between miR-34 dysregulation and distant metastases formation in lung adenocarcinoma.
Lung cancer has the highest mortality rate amongst human cancers and the majority of deaths can be attributed to metastatic spread. The miR-34 family includes three tumor suppressive miRs: miR-34a, miR-34b and miR-34c. miR-34 downregulation is a frequent observation in human malignancies and is often attributed to hypermethylation of the miR-34a and miR-34b/c promoters. Here, the potential association between aberrant miR-34 expression and promoter methylation and distant metastases formation in lung adenocarcinoma (LAC) is investigated. The expression levels of miR-34a, miR-34b and miR-34c, as well as the methylation status of the miR-34a and miR-34b/c promoters were determined in a LAC patient cohort comprising 26 non-metastasizing and 26 metastasizing primary LACs, as well as 24 paired distant metastases and 25 tumor-adjacent normal lung samples using RT-qPCR and Methylation-Sensitive High Resolution Melting (MS-HRM) analysis. No difference in expression was observed for miR-34a when comparing metastasizing and non-metastasizing LACs (p=0.793). For both miR-34b and miR-34c, a significantly lower expression level was determined in metastasizing LACs compared to non-metastasizing LACs (p=0.0005 and p=0.002) with similarly decreased expression levels observed in the paired distant metastases. Hypermethylation was detected in 35/51 LACs compared to 0/25 tumor-adjacent normal lungs for the miR-34a promoter (p<0.0001). Similarly, 18/51 LACs compared to 1/25 tumor-adjacent normal lungs showed hypermethylation of the miR-34b/c promoter (p=0.003). No difference in methylation was observed between metastasizing and non-metastasizing LACs for neither the miR-34a (p=0.832) nor the miR-34b/c (p=0.900) promoter. In conclusion, miR-34a and miR-34b/c promoter hypermethylation is a frequent event in LAC occurring in 68.7% and 35.3% of tested cases (n=51), respectively. Low miR-34b and miR-34c expression was associated with distant metastases formation in LAC. These changes can be targeted as novel biomarkers in LAC.


Diagnostic usefulness and limitations of the sural nerve biopsy.
In recent years, the sural nerve biopsy has become a commonly performed procedure in the diagnostic work-up of patients with peripheral neuropathy. This paper reviews the diagnostic usefulness and limitations of this procedure. Based on 385 sural nerve biopsies, we found clinically helpful or relevant information in 45% of cases. In 24% of cases, specific diagnoses were obtained, among which vasculitic neuropathy was most common.


Patterns of care of radiation therapy in patients with stage IV rectal cancer: a Surveillance, Epidemiology, and End Results analysis of patients from 2004 to 2009.
According to the 2013 National Comprehensive Cancer Network guidelines, pelvic radiation therapy (RT) is one of the preferred regimens for patients with metastatic rectal cancer (mRC). The objective of this study was to analyze patterns of care and outcomes data for the receipt of RT among patients with mRC using the Surveillance, Epidemiology, and End Results (SEER) database. Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (2004-2009). Patients were stratified according to their primary disease site (rectum vs rectosigmoid), tumor (T) classification, and lymph node (N) classification. Treatment regimens (with or without surgical resection, with or without RT) were recorded. The Fisher exact test was used to compare RT rates based on stratified factors. Two and five-year survival rates were compared among treatment groups. In total, 6873 patients with stage IV rectal cancer and 3417 patients with rectosigmoid cancer were identified. Overall, 20.5% of patients with rectal cancer underwent surgery alone, whereas 38.7% received RT with or without surgery. Within the rectosigmoid group, 51.4% of patients underwent surgery alone, and 15.1% received RT with or without surgery. The use of RT differed significantly between patients with in situ (Tis) through T2 tumors versus T3/T4 tumors (P < .001) and between those with N0 disease versus N1/N2 disease (P < .001). The 2-year and 5-year survival rates differed between treatment groups, with the highest survival rates observed among those who received combined surgery and RT. The primary treatments for patients with mRC include RT with or without surgery. RT is used more commonly in patients with primary rectal (vs rectosigmoid) tumors, N0 disease, or Tis-T2 tumors. Treatment with combination surgery and RT is associated with prolonged survival.


[Effects of Ligustrazine Injection on Serum Cys C Level in Scierema Neonatorum Children Patients].
Objective To observe the effects of Ligustrazine Injection (LI) on serum cystatin C (Cys C) level in sclerema neonatorum (SN) children patients. Methods Totally 69 SN children patients were recrui- ted as the SN group, 39 with mild SN and 30 with moderate-severe SN. Another 30 neonates were recruited as a control group. Mild SN children patients and moderate-severe SN children patients were respectively assigned to the treatment group and the routine group according to random digit table. Children patients in the routine group received routine supportive treatment and symptomatic treatment, while those in the treatment group were additionally injected with LI (6 mg/kg, adding in 30 mL 5% glucose injection; once per day). All treatment lasted for 7 successive days. Serum level of Cys C, blood urea nitrogen (BUN) , and creatinine (Cr) were detected. The abnormality rate of Cys C, BUN, and Cr was respectively calculated, and their correlations analyzed. Meanwhile, scleroma subsidence time was observed in each group. Results The serum level of Cys C was obviously elevated more in the SN group than in the control group (t =10. 55, P <0. 01). There was no statistical difference in serum level of BUN or Cr between the control group and the SN group (t =1.50, 1. 73; P >0. 05). Serum Cys C level obviously increased in moderate-severe SN children patients than in mild SN children patients (t =2. 11 , P <0. 05); serum levels of BUN and Cr showed increasing tendency in moderate-severe SN children patients and mild SN children patients, but with no statistical difference (t =2. 07, 1. 92; P >0. 05). Linear correlation showed that serum Cys C level was respectively positively correlated with serum BUN level and serum Cr level in the SN group (r =0. 314,0. 287,P <0. 05). The abnormality rate of serum Cys C, BUN, and Cr was 72. 5% (50/69), 27. 5% (19/69), and 36. 2% (25/69), respectively. The abnormality rate of serum Cys C was significantly higher than that of BUN or Cr (x² =41. 04; P <0. 01). Compared with the routine group, serum Cys C level and scleroma subsidence time were obviously lowered in moderate-severe SN chil- dren patients and mild SN children patients of the treatment group (P <0. 05), but with no statistical difference in serum level of BUN or Cr (P >0. 05). Conclusions Serum Cys C level could reflect early renal injury in SN children patients. But LI could obviously reduce serum Cys C level, promote the recovery of renal injury of SN neonates, and shorten scleroma subsidence time.


Specific inhibition of phagosome-lysosome fusion in murine macrophages mediated by Salmonella typhimurium infection.
Phagosome-lysosome fusion in murine macrophages infected with S. typhimurium LT2 or S. typhi 1079 was investigated. Fusion of phagosome containing S. typhimurium LT2 with lysosome was markedly impaired, whereas S. typhi 1079 did not inhibit phagosome-lysosome fusion in murine macrophages. A similar inhibition of fusion was observed with LPS-deficient mutants of S. typhimurium LT2, suggesting that O-antigens do not contribute to the inhibition of fusion. Phagosome-lysosome fusion in macrophages after ingestion of UV-killed S. typhimurium LT2 was much greater than that of live bacteria. Furthermore, treatment of S. typhimurium LT2 with streptomycin, an inhibitor of bacterial protein synthesis, caused an increase in the extent of phagosome-lysosome fusion. Therefore protein synthesis in live bacteria is probably required for the inhibition of phagosome-lysosome fusion. These results suggest that phagosome-lysosome fusion in murine macrophages is impaired by some product(s) of viable S. typhimurium LT2.


Maternal country of origin and infant birthplace: implications for birth-weight.
This study investigated the effect of mother's country of origin and baby's birthplace on infant birth-weight. The mean birth-weights of full-term babies born of well immigrant women from 5 countries were compared with those of women of Anglo-Australian origin confined at the same hospital. Data were collected from medical records at Canterbury hospital for 1,274 women confined between 1989 and 1992 and 2,524 of their babies. Multiple regression analysis showed that infants born in Australia to women from Vietnam and Korea were significantly heavier than infants born to these women in their country of origin. Babies born to women from Vietnam were significantly lighter than babies born to Anglo-Australian controls.


The effects of fluorocitrate on renal glutamine, lactate, alanine, and oxygen metabolism in the dog.
Acid-base status is considered the major factor controlling renal NH4+ production from glutamine, with maximal values found in chronic acidosis. However, metabolic inhibitors have been shown to increase NH4+ production without acid-base change; the mechanism for this increase is unclear. Fluorocitrate was administered to dogs with chronic metabolic alkalosis. Following fluorocitrate total renal NH4+ production rose from 32 +/- 5 to 104 +/- 15 mumol/(min.100 mL glomerular filtration rate (GFR] (p less than 0.01) and glutamine extraction rose from 26 +/- 8 to 65 +/- 8 mumol/(min.100 mL GFR) (p less than 0.01). These values approximate maximal values found in chronic acidosis. Lactate utilization fell from 165 +/- 19 to 99 +/- 7 mumol/(min.100 mL GFR) following fluorocitrate (p less than 0.01). Citrate extraction fell to zero and alanine production rose from 27 +/- 4 to 46 +/- 7 mumol/(min.100 mL GFR) (p less than 0.01). Oxygen consumption remained unchanged following fluorocitrate, 584 +/- 29 vs. 549 +/- 29 mumol/(min.100 mL GFR). These results demonstrate that in the presence of metabolic inhibition in the kidney, ATP production remains constant. This is achieved by increased utilization of one substrate, glutamine, when the ATP production from other substrates is reduced. Thus the necessity to maintain constant ATP production appears to modulate renal NH4+ production.


Topical delivery of long-acting antiretrovirals to prevent HIV acquisition.
Although tremendous successes in HIV treatment and prevention have occurred in the past decade, existing HIV prevention options are inadequate, unacceptable or inaccessible to many. Topical antiretroviral-based preexposure prophylaxis (PrEP) options may offer effective, long-acting prevention to those who do not desire systemic exposure to anti-HIV drugs or who want greater control over their own prevention. Among long-acting topical PrEP agents, the dapivirine vaginal ring has advanced the furthest in product development; recent studies have shown high adherence and persistence and evidence of HIV protection in open-label studies as well as a well tolerated safety profile, across the life cycle in women. A range of other long-acting topical PrEP products for vaginal or rectal drug delivery are under development. Rigorous end-user research has explored how to develop products that are behaviorally congruent for the population at risk and has shown that no single product option will be desired by all, but rather different options will achieve the greatest prevention coverage. Topically delivered, long-acting antiretroviral PrEP options are being designed to align with user preferences and lifestyles, providing the potential to more effectively expand the HIV prevention method mix and use and achieve an important impact on HIV globally.


Isolation and characterization of AAP1. A gene encoding an alanine/arginine aminopeptidase in yeast.
The yeast AAP1 gene, encoding a putative amino-peptidase, was isolated based on its ability to suppress the temperature-sensitive growth on nonfermentable carbon sources of spr5, a stationary phase regulatory mutant. AAP1 was physically mapped to chromosome VIII between PUT2 and CUP1. Sequence analysis of the AAP1 gene showed a 1581-nucleotide open reading frame capable of encoding a 59-kilodalton protein. The protein encoded by this open reading frame exhibits approximately 40% sequence identity to human, rat, and mouse aminopeptidases. In limited regions, sequence identity between Aap1 and the mammalian aminopeptidases ranges from 53% to 93%. Insertional inactivation of the AAP1 gene resulted in a decrease in glycogen accumulation and the loss of the major band of arginine/alanine aminopeptidase activity. Strains carrying the AAP1 gene on a high copy plasmid show an increase in the major arginine/alanine aminopeptidase activity, a dramatic increase in glycogen accumulation, and an increase in transcription from a vector carrying lacZ fused to the promoter of a gene (SSA3) expressed during post-diauxic and stationary phases of the culture cycle. We conclude that although the AAP1 gene is not essential for viability, the Aap1 protein positively affects glycogen accumulation in yeast.


Evidence for Targeting Low-Molecular-Weight Proteins in Hemodialysis and Hemodiafiltration.
With the identification of β2-microglobulin (β2MG) as an active participant in dialysis-related amyloid fibril formation, low-molecular-weight proteins (LMWPs) are now recognized as a distinct class of uremic toxins, and numerous compounds in this category have been identified. The class of LMWPs, although not precisely defined, has a molecular weight range of approximately 1,000-50,000 Da. With this in mind, dialysis prescriptions have been modified to increase the efficiency of uremic solute removal. Many studies have characterized the dialytic removal of β2MG and it is therefore regarded as a surrogate for LMWPs. In Japan, dialysis membranes that can efficiently remove β2MG are recommended. Recently, researchers have reported that β2MG is not only a uremic toxin that should be removed, but also a predictor of the prognosis of dialysis patients. In Japan, hemodiafiltration (HDF), especially on-line HDF, and protein-permeable hemodialysis (HD) is being actively carried out, and it is often reported that prognosis is improved by decreasing the concentrations of substances larger than β2MG. It is important, then, that dialysis prescriptions achieve effective clearance of such substances. Key Messages: Over 2,000 uremic substances have been identified that form or accumulate because of renal failure and cause various symptoms and complications. Focusing on these facts, HD or HDF therapy, which is associated with albumin loss, was implemented targeting the LMWPs. Here, we report the effects of albumin-losing blood purification (HD/HDF) for the purpose of removing LMWPs.


Kronig-Penney model for periodically segmented waveguides.
Physical insight into the propagation characteristics of periodically segmented waveguides can be obtained by viewing the guiding layer as a thin slab of an idealized infinite medium with periodic layers along the direction of propagation. One can analyze the properties of this infinite medium using a formal analogy with the Kronig-Penney model used to describe the propagation of electron wave functions in a periodic crystal potential. The model correctly gives the effective refractive index of the layer, gives insight into the electric field profiles at different points on the dispersion curve, and leads to a qualitative explanation of why the optical loss diminishes at both large and small duty cycles.


Tumor antigen expression in melanoma varies according to antigen and stage.
Melanoma cells express antigens that can induce T-cell and antibody responses. Obtaining a detailed understanding of antigen expression in primary and metastatic melanoma is essential if these molecules are to be useful targets for immunotherapy of melanoma. Malignant melanomas (n = 586) from 426 patients were typed for antigen expression. Multiple samples were available from 86 individuals, enabling analysis of antigen expression patterns over time. Paraffin-embedded samples were tested by immunohistochemistry for the presence of the differentiation antigens: gp100, Melan-A, tyrosinase, and the "cancer/testis" antigens MAGE-A1, MAGE-A4, and NY-ESO-1. Samples were primary tumors (n = 251), lymph node metastases (n = 174), s.c. metastases (n = 71), and distant metastases (n = 90). The differentiation antigens were strongly expressed in 93% to 95% of tumors regardless of stage. In contrast, the frequency of cancer/testis antigen expression in primary tumors for MAGE-A1, MAGE-A4, and NY-ESO-1 was lower (20%, 9%, and 45%, respectively). MAGE-A1 and MAGE-A4 were acquired with advancing disease (to 51% and 44% in distant metastases, respectively) but not NY-ESO-1, which remained positive in 45%. MAGE-A1 expression was twice as prevalent in ulcerated primaries as in nonulcerated primaries (30% versus 15%; P = 0.006) and in thicker as opposed to thin melanomas (26% versus 10%; P = 0.1). This large series describes patterns of antigen expression in melanoma and their evolution over time. This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials.


Cocaine use among American adolescents and young adults.
In this chapter, we have tried to provide some objective information about the levels of and recent trends in cocaine use among America's adolescents and young adults, as well as some of their attitudes and beliefs about the drug and their reasons for using it. We have also examined cross-time patterns of use, certain predictors of use, and some of the conditions of the social and physical environments which are associated with use. Overall, we have found levels of use to be relatively stable for the past several years after a period of rapid increase between 1976 and 1979. We also found a strong age effect, with cocaine use increasing in the first few years after high school. The levels of use, though stable recently, are disturbingly high, particularly among young adults in their early to mid twenties. Self reported use has followed patterns that parallel exposure to use and use by friend, as would be expected, assuming valid measures. Perceived availability also has moved in tandem with these other measures. The great majority of today's seniors believe regular use to be dangerous, and 77% disapprove of even experimenting with cocaine. Use is found most frequently in the western and northeastern regions of the country, in more urban areas, among males, and among those who are not college-bound. Neither socioeconomic status nor personal income are very strongly associated with use; but a history of truancy, going out frequently in the evenings, and having relatively low religious involvement are. Cocaine users tend to use other illicit drugs (particularly marijuana) and to be cigarette smokers and heavy drinkers much more frequently than nonusers. Thus, there is little evidence that cocaine involves a separate drug-using syndrome. In fact, it is not uncommon for cocaine users to use marijuana or alcohol concurrently. When taking cocaine, high school students most often snort it, though some (24% of recent users) smoke it while only 4% of the users inject it. It is almost always used with other people present, often at a party but more often with just one or two people present. Most use occurs in the evening, with very few young people using at school and a minority ever using at home or in a car. Among the reasons most often cited for using cocaine use are: "to see what it's like," "to get high," and "to have a good time with my friends."(ABSTRACT TRUNCATED AT 400 WORDS)


A systematic review of the effectiveness of bowel management strategies for constipation in adults with stroke.
Constipation is one of the most common medical complications of acute stroke. Currently, management strategies to guide clinical practice are limited. This review aimed to examine the effectiveness of bowel management strategies for constipation in adults with stroke. A systematic review of randomised controlled trials or other quantitative research designs in the absence of randomised controlled trials was undertaken. A comprehensive search of major electronic databases and all reference lists of relevant articles in the English language were performed from January 1990 up to March 2011. Data were extracted and assessed by two independent reviewers. Due to differences in the study designs, the findings are presented in narrative form. There were a total of three studies (two randomised controlled trials and one quasi-experimental study). One of the randomised controlled trials examined a single (once-only) structured nurse-led intervention and the other randomised controlled trial evaluated four bowel management programmes. Both studies yield improvements respectively in symptoms of bowel dysfunction and bowel training efficiency when the programme corresponded with the subjects' bowel patterns before the stroke onset. The quasi-experimental study compared the effectiveness of daily digital stimulation versus every other day and found higher bowel regularity with daily digital stimulation. Constipation management strategies are limited. This review suggests that structured bowel programmes and nurse-led intervention in bowel care have a significant effect in improving bowel evacuations.


A micro-CT approach for determination of insect respiratory volume.
Variation in the morphology of the insect tracheal system can strongly affect respiratory physiology, with implications for everything from pest control to evolution of insect body size. However, the small size of most insects has made measuring the morphology of their tracheal systems difficult. Historical approaches including light microscopy and scanning and transmission electron microscopy (SEM, TEM) are technically difficult, labor intensive, and can introduce preparation artifacts. More recently, synchrotron X-ray microtomography (SR-μCT) has allowed for detailed analysis of tracheal morphology of diverse insects. However, linear accelerators required for SR-μCT are not readily available, making the approach unavailable for most labs. Recent advancements in microcomputed tomography (μCT) have made possible fine resolution of internal morphology of very small insects. However, μCT has never been used to quantify insect tracheal system dimensions. We measured respiratory volume of a grasshopper (Schistocerca americana) by analysis of high resolution μCT scans. Volume estimates from μCT closely matched volume estimates by water displacement as well as literature estimates for this species. The μCT approach may thus provide a widely available, cost-effective, and straightforward approach to characterizing the internal morphology of insect respiratory systems.


The hospice: Humane care for the dying.
The hospice movement arose as a reaction to the dehumanizing atmosphere of acute-care hospitals, where excessive utilization of life support equipment deprived dying patients of a meaningful vision of their destiny. Respecting the spiritual quest of the terminally ill for wholeness and dignity, the hospice concept prescribes the rendering of compassionate and pastoral care by a benevolent community of family, health care staff, friends, and clergy. Approximately 800 hospice programs are currently evolving in the United States. St. Mary's (formerly "Hillhaven") Hospice in Tucson, Arizona, offers the most comprehensive program of services, including home care, inpatient care, and artistic media through which the dying express their creativity. Numerous demonstration projects funded by several government agencies, principally the Health Care Financing Administration (HCFA), are expected to result in legislative actions eliminating barriers to reimbursement of the cost of hospice services by Medicare, Medicaid, and other third-party payers. Existential analysis reveals the value of religion and spiritual support in enabling the dying to banish anxiety and muster the hope requisite for fully appreciating the authentic meaning of their destiny.


Strain Multiplexed Metasurface Holograms on a Stretchable Substrate.
We demonstrate reconfigurable phase-only computer-generated metasurface holograms with up to three image planes operating in the visible regime fabricated with gold nanorods on a stretchable polydimethylsiloxane substrate. Stretching the substrate enlarges the hologram image and changes the location of the image plane. Upon stretching, these devices can switch the displayed holographic image between multiple distinct images. This work opens up the possibilities for stretchable metasurface holograms as flat devices for dynamically reconfigurable optical communication and display. It also confirms that metasurfaces on stretchable substrates can serve as platform for a variety of reconfigurable optical devices.


Effect of omega-3 fatty acids on canine atopic dermatitis.
Twenty-nine dogs were included in a double-blinded, placebo-controlled, randomised trial and were orally supplemented for 10 weeks with either flax oil (200 mg/kg/day), eicosapentaenoic acid (50 mg/kg/day) and docosahexaenoic acid (35 mg/kg/day) in a commercial preparation, or mineral oil as a placebo. For each dog, clinical scores were determined based on a scoring system developed prior to the trial. Total omega-6 and omega-3 intake and the ratio of omega-6:omega-3 (omega-6:3) were calculated before and after the trial. The dogs' clinical scores improved in those supplemented with flax oil and the commercial preparation, but not in the placebo group. No correlation was identified between total fatty acid intake or omega-6:3 ratio and clinical scores. Based on the results of this study, the total intake of fatty acids or the omega-6:3 ratio do not seem to be the main factors in determining the clinical response.


Allee effects in ants.
1. Allee effects occur when the aggregation of individuals result in mutually beneficial intraspecific interactions whereby individual fitness, or per capita growth rate, increases with the number of individuals. Allee effects are common in social species due to their cooperative behaviours, such as breeding, feeding or defence. Allee effects have important implications for many aspects of basic and applied ecology. Over the past decades, the study of Allee effects has influenced population dynamics, community ecology, endangered species management and invasion biology. 2. Despite the fact that cooperation is the basis of their social structure, Allee effects have received little attention among eusocial insects. Extreme cooperation is common, and reproductive specialization of individuals occurs due to division of labour. These life-history traits suggest that the potential contribution of each caste to reproduction and survival may be differential and nonadditive. 3. We studied Allee effects in the invasive Argentine ant (Linepithema humile). In this species, many queens and workers are present in colonies, which allowed us to explore the differential effects of castes on the presence of Allee effects. In the laboratory, we measured brood production and individual survival in experimental colonies that differed in the initial numbers of queens and workers.4. Our results highlight the differential effect of queens and workers on survival and productivity. We found three positive density-dependent relationships indicative of component Allee effects at the colony level: both workers and queens had a positive effect on the productivity of the other caste, and queens had a positive effect on worker survivorship. 5. Our experimental results suggest a potential positive feedback between worker and queen abundance, which may have contributed to the evolution of large colony sizes. Our study provides the first evidence of Allee effects in eusocial insects and highlights the need to consider castes separately in population dynamics. Division of labour and differential reproductive rates are factors that should be integrated into the study of Allee effects.


High school athletic participation, sexual behavior and adolescent pregnancy: a regional study.
To determine whether high school athletic participation among adolescents in Western New York was associated with reduced rates of sexual behavior and pregnancy involvement. A secondary analysis of data from the Family and Adolescent Study, a longitudinal study of a random sample of adolescents (ages 13-16 years) from 699 families living in households in Western New York. A general population sample was obtained with characteristics closely matching the census distributions in the area. Interview and survey methods provided data on athletic participation, frequency of sexual relations during the past year, and risk for pregnancy. Bivariate correlations were used to examine relationships among athletic participation, demographic and control variables, and measures of sexual behavior and pregnancy rates. Next, path analyses were done in order to test for hypothesized relationships between athletic participation, sexual behavior, and pregnancy involvement while controlling for age, race, income, family cohesion, and non-athletic forms of extracurricular activity. Variables that were significantly associated with sexual behavior and/or pregnancy involvement were presented for both sexes within the resulting multivariate models. Lower income and higher rates of sexual activity were associated with higher rates of pregnancy involvement for both sexes. Family cohesion was associated with lower sexual activity rates for both sexes. For girls, athletic participation was directly related to reduced frequency of sexual behavior and, indirectly, to pregnancy risk. Male athletes did not exhibit lower rates of sexual behavior and involvement with pregnancy than male non-athletes. Boys who participated in the arts, however, did report lower rates of sexual behavior and, indirectly, less involvement with pregnancy. Female adolescents who participated in sports were less likely than their non-athletic peers to engage in sexual activity and/or report a pregnancy. Among male adolescents, athletic participation was unrelated to sexual behavior and pregnancy involvement. Teen pregnancy prevention efforts for girls should consider utilizing sport as a strategic tool.


Genetics of diabetic nephropathy.
Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alterations, and various growth factors and genetic factors. Epidemiologic and family studies have demonstrated that only a subset of the patients develop this complication that family clustering of nephropathy is present, and that ethnicity plays an important role in the risk of developing this kidney disease. Short stature and low birth weight are both associated with increased risk of developing diabetic nephropathy, supporting the hypothesis that genetic predisposition or factors operating in utero, in early childhood, or both contribute to the development of diabetic nephropathy. Studies elucidating phenotypic markers such as parenteral hypertension and systemic blood pressure elevation have yielded conflicting results. The contribution from elevated blood pressure only plays a minor role in the majority of the patients developing diabetic nephropathy. The majority of the studies have demonstrated increased sodium/lithium countertransport activity in insulin-dependent diabetes mellitus patients with nephropathy, whereas studies of this phenotypic marker in parents of patients with and without nephropathy have yielded conflicting results. Recently, studies of genetic markers involved in the regulation of blood pressure and levels of cardiovascular risk factors have been conducted. Several studies have demonstrated that the deletion polymorphism in the angiotensin-I-converting enzyme acts as a risk factor for cardiovascular disease in diabetic patients. However, a meta-analysis does not support the suggestion that this factor plays any role for the initiation of diabetic nephropathy. Similar negative results have been obtained in relation to polymorphisms of the genes encoding for angiotensinogen and the angiotensin II Type 1 receptor. However, studies in diabetic and non-diabetic glomerulopathies have clearly demonstrated a deleterious effect of the deletion polymorphism in the angiotensin-converting enzyme on the progression of kidney function.


Enrollment and Retention in 34 United States Pregnancy Registries Contrasted with the Manufacturer's Capture of Spontaneous Reports for Exposed Pregnancies.
Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy. The aim of this study was to evaluate postmarket capture of exposed pregnancies. Pregnancy registries for drugs and biologics were identified in a systematic review. Through a standardized questionnaire, manufacturers provided information on (1) pregnancy registry enrollment and retention, and (2) worldwide receipt of spontaneous reports for exposed pregnancies. A validated algorithm for live-birth pregnancies allowed calculation of exposure rates per 100,000 live births using claims data. Among 34 products with a pregnancy registry, median (interquartile range) registry enrollment was 36 pregnancies (5-258) and median spontaneous report capture was 450 pregnancies (89-1192). Products used in >20/100,000 live births had a median registry enrollment of 490 pregnancies and median capture of 1061 spontaneously reported exposed pregnancies. Lower median registry enrollment and spontaneous report capture was observed for products used in 0.5-20/100,000 live births (36 from registries, 541 spontaneous reports) and <0.5/100,000 live births (3 from registries, 41 spontaneous reports). Among 24 registries enrolling ≥10 pregnancies, median capture of pregnancy outcomes (e.g. live birth, spontaneous abortion) was 83.9%. For 19 registries enrolling ≥10 infants, the median proportion of infants achieving protocol-specified follow-up was 89.9% for up to 4 weeks post-birth, 75.0% for 1-5 months, and 57.1% for ≥6 months. Relatively higher product utilization among pregnant women predicted greater pregnancy registry enrollment. For products rarely used during pregnancy, registry enrollment was low and differences in registry enrollment compared with worldwide spontaneous report receipt were most pronounced. Products with very low utilization levels during pregnancy may require a combination of worldwide pharmacovigilance, pregnancy registries, and additional study methods to achieve adequate surveillance.


Self-amplification of nigral degeneration in Parkinson's disease: a hypothesis.
This review analyzes current evidence regarding possible mechanisms of nigral damage in idiopathic Parkinson's disease (iPD). In normal brain, a specific interplay among the blood-brain barrier (BBB), substantia nigra (SN), and locus coeruleus (LC) creates the condition for a self-accelerating damage to the SN. Three vicious circles involving SN-BBB, LC-SN-BBB, and histamine-BBB-SN interactions are described. In iPD, a self-accelerating loss of nigral cells can be triggered by brain hypoperfusion and by an increased blood histamine level. iPD-associated factors such as decreased CSF levels of substance P, somatostatin, and glutamate can aggravate the vicious-circle-induced damage to the SN.


A model for assortative mating.
It is shown that a generalization of the Hardy-Weinberg law of the proportions of genotypes of the kind given by Wright (1922) is maintained in equilibrium by a pattern of assortative mating suggested by Fisher (1918) and elaborated by Malécot (1939, 1948).


Unusual case of right-sided May-Thurner syndrome and review of its management.
May-Thurner syndrome is a phenomenon commonly described as an acquired stenosis of the left common iliac vein as a result of right common iliac artery compression. We report an unusual case of right-sided May-Thurner syndrome in a patient found to have a left-sided inferior vena cava. We also review the management of this patient using angioplasty, intraoperative thrombolysis, and endoluminal stent placement.


Acute airway management in the critically ill child requiring transport.
Airway compromise was found to be a common problem in children requiring critical care transport to our hospital. This retrospective review of 39 infants and children was undertaken to assess the frequency and degree of airway compromise in these children, to document the management required and to determine who performed it. Ninety-seven per cent of children had airway difficulties associated with their disease, and one-third of these required further airway management on the arrival of the transport team. Airway specialists had not been involved in the care of these children before the arrival of the transport team. This indicates that greater attention should be paid to airway management as soon as children are identified as being sufficiently ill to require transport to a tertiary care facility.


The effect of different isolation protocols on detection and molecular characterization of Campylobacter from poultry.
We determined whether different methods to isolate Campylobacter (including the ISO standard 10272:2006-1) affected the genotypes detectable from poultry, at three points during slaughter: caecal content, neck skin and meat. Carcasses from 28 independent flocks were thus sampled (subset A). In addition, ten neck skin samples from four flocks, ten caecal samples from ten different flocks and ten unrelated meat samples obtained from local supermarkets were collected (subset B). Campylobacter was isolated using eight different protocols: with and without enrichment using Bolton broth, Preston broth or Campyfood broth (CFB), followed by culture on either modified Charcoal Cefoperazone Deoxycholate Agar (mCCDA) or Campyfood agar (CFA). All obtained isolates were genotyped for flaA-SVR, and over half of the isolates were also typed by MLST. The strain richness, as a measure of number of detected fla-genotypes, obtained from subset A neck skin and caecal samples was higher than that of meat samples. In half of the cases, within a flock, at least one identical fla-genotype was obtained at all three slaughter stages, suggestive of autologous contamination of carcasses. Enrichment reduced the observed richness of isolates, while CFA plates increased richness compared to mCCDA plates, irrespective of inclusion of an enrichment step. Because the isolation protocol used influences both the yield and the fla-genotype richness obtained from poultry, this variable should be taken into account when different studies are being compared.


Rapid and area-specific coating of fluoride-incorporated apatite layers by a laser-assisted biomimetic process for tooth surface functionalization.
Surface functionalization of teeth with fluoride-incorporated apatite layers displays great potential in treatments and prevention of dental disorders. In this study, we used a sintered hydroxyapatite (sHA) substrate as a model material of teeth, and established a rapid and area-specific coating technique of fluoride-incorporated apatite layers by using a laser-assisted biomimetic (LAB) process. In this technique, a sHA substrate was irradiated on the surface with a Nd:YAG pulsed UV laser for 30 min in supersaturated calcium phosphate (CaP) solutions with various fluoride concentrations. The fluoride concentration in the CaP solution was varied to control morphology, crystalline structure, and fluoride content of the resulting layers. Without fluoride in the CaP solution, an octacalcium phosphate (OCP) layer with a flake-like structure was formed on the laser-irradiated surface of the substrate. The addition of fluoride (1000 µM and 3000 µM) to the CaP solution led to the formation of fluoride-incorporated apatite layers with an enamel-like needle-like nanostructure. The fluoride-incorporated apatite layers adhered firmly to the sHA surface and reduced acid dissolution of the sHA substrate by acting as a protective covering. Additionally, the layers released fluoride ions for more than 24 h, and exhibited antibacterial activity relative to a caries-causing bacterium, namely Streptococcus mutans. Thus, our LAB process can potentially act as a new tool for functionalization of tooth surfaces. We used a sintered hydroxyapatite (sHA) substrate as a model material of teeth, and established a rapid and area-specific coating technique of fluoride-incorporated apatite layers on the sHA surface by using our laser-assisted biomimetic (LAB) process. In this process, pulsed laser was utilized to accelerate seeded crystal growth in supersaturated calcium phosphate solutions supplemented with NaF. The thus-fabricated fluoride-incorporated apatite layers consisted of enamel-like needle-like nanocrystals with c-axis orientation. These fluoride-incorporated apatite layers adhered firmly to the sHA surface, reduced acid dissolution of the sHA substrate by acting as a protective covering, and exhibited antibacterial activity against Streptococcus mutans through the fluoride release. Thus, our LAB process can potentially act as a new tool for functionalization of tooth surfaces.


Very delayed cervical lymph node metastases from hyalinizing clear cell carcinoma: report of 2 cases.
Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm most often found in the oral cavity. Although it is generally a low-grade malignancy that is treated with wide local excision, there is a growing body of evidence pointing toward the potential for more aggressive behavior. We reviewed available records of patients with delayed cervical lymph node metastases from HCCC. Two patients who were treated with wide local resection for HCCC and remained disease-free at the primary site were diagnosed with cervical lymph node metastases 10 and 14 years later. We treated both with neck dissection, and 1 patient received adjuvant radiation therapy. These cases illustrate the risk for occult nodal metastases from HCCC with delayed presentation. Clinician awareness of the presence of subclinical metastases in the neck requires thorough long-term surveillance and potential intervention should nodal disease become manifest.


Changes in serum inhibin, activin and follistatin concentrations during puberty in girls.
Serum concentrations of inhibin A, inhibin B, activin A and follistatin were determined using two-site enzyme-linked immunosorbent assays (ELISA) during pubertal ovarian development in 28 girls and five follicular phase women. Blood obtained every 15 to 20 min overnight was pooled for peptide determination. Serum inhibin A concentrations increased in mid puberty, exhibiting positive correlations with bone age (r = 0.527, P = 0.0016) and oestradiol concentrations (r = 0.581, P = 0.0005). Inhibin B concentrations peaked in mid puberty and declined thereafter, but remained greater than concentrations seen in prepubertal girls, and correlating positively with oestradiol (r = 0.362, P = 0.046) and follicle stimulating hormone (FSH) concentrations (r = 0.369, P = 0.038). Total activin A concentrations did not vary significantly across pubertal stages. Total follistatin concentrations, determined by radioimmunoassay, decreased with advancing puberty, exhibiting negative correlations with bone age (r = -0.634, P = 0.0001) and oestradiol concentration (r = -0.687, P = 0.0001). Follistatin concentrations determined by an ELISA specific for follistatin 288 were greatest in mid-pubertal girls, but concentrations in late puberty were less than those in early puberty. The free follistatin assay indicated that all circulating follistatin was activin-bound. These results suggest that significant changes in serum concentrations of FSH-regulatory peptides accompany the onset of puberty.


Fiber-supplemented enteral formula slows intestinal transit by intensifying inhibitory feedback from the distal gut.
Because an increase in flow rate accelerates intestinal transit, a reduction in the flow rate of formula delivery is recommended frequently for treatment of diarrhea that develops during enteral feeding. Because intestinal transit is slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit during enteral feeding may depend on a balance between the accelerating effect of flow and the inhibiting effect of the nutrient load. The addition of fiber to a formula may alter this balance. By delaying absorption of nutrients, fiber may extend the length of small intestine exposed to nutrients and thereby trigger more intense inhibitory feedback. To determine whether the addition of fiber favors nutrient-triggered inhibition over flow-driven acceleration, we studied intestinal transit after perfusion of a low-residue enteral formula compared with a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into the duodenum of dogs each with both a duodenal and midgut fistula. With the low-residue formula, intestinal transit accelerated when the flow rate increased from 50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however, intestinal transit was inhibited regardless of the flow rate. To determine whether the fiber-supplemented formula inhibited intestinal transit by displacing nutrients distally, we compared intestinal transit when the two formulas, delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal transit of the fiber-supplemented formula increased by 400%, eliminating the difference in intestinal transit speed between the two formulas. We concluded that the fiber-supplemented formula slowed intestinal transit by intensifying inhibitory feedback from the distal gut.


Individual variability of the cutaneous larva migrans (CLM) incubation period.
Whether the high variable incubation period of cutaneous larva migrans depends on the parasite or other host factors remains unknown. Two brothers were contaminated simultaneously, but had 15- and 165-day incubation periods, respectively, suggesting a possible influence of host factors. A long incubation period does not rule out cutaneous larva migrans in patients with creeping eruption.


Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 ( FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes.
The present study gives further evidence for the recently found association between variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and PUFA in blood phospholipids and explores this association for cellular fatty acids in erythrocyte membranes. In a subgroup of adults participating in the Bavarian Nutrition Survey II, a cross-sectional population-based study conducted in Bavaria, Germany, allelic variation in three selected loci of the FADS1 FADS2 gene cluster was analysed and used for haplotype construction. Associations with plasma phospholipid PUFA (n 163) and PUFA in erythrocyte membranes (n 535) were investigated by regression analysis. All haplotypes of the original five-loci haplotypes of our previous study could be replicated. In addition, associations with serum phospholipid PUFA were confirmed in the present data set. Although less pronounced, associations between FADS1 FADS2 haplotypes and PUFA in erythrocyte membranes, particularly arachidonic and dihomo-gamma-linolenic acid, could be established. We provide the first replication of the association of the FADS1 FADS2 gene cluster with PUFA in blood phospholipids. For the first time, such associations were also shown for PUFA in cell membranes.


Novel targets for malaria therapy.
Malaria has emerged as one of the most debilitating parasitic infection with about 500 million cases reported annually and one million deaths worldwide. Currently, Plasmodium falciparum has developed resistance to almost all classes of antimalarials, thus precluding the use of those agents which once formed the cornerstone of malaria therapy. In lieu of this phenomenon, and taking into consideration the absence of an effective vaccine for malaria, the only way to combat the deadly parasite is to enrich the antimalarial cache with new molecules acting on fresh targets in the parasite. After potential targets have been validated, these targets can be used as basis for screening compounds to identify new leads followed by lead optimization. This review discusses novel targets of the malaria parasite that can be utilized to treat the disease.


Reversible Membrane Tethering by ZipA Determines FtsZ Polymerization in Two and Three Dimensions.
In most bacteria, the early step of septum formation implies the association of soluble FtsZ polymers with the cytoplasmic membrane. ZipA, together with FtsA, provides membrane tethering to FtsZ in Escherichia coli, forming a dynamic proto-ring that serves as an assembly scaffold for the remaining elements of the divisome. Despite their importance for bacterial cell division, multivalent interactions between proto-ring elements at membrane surfaces remain poorly characterized in quantitative terms. We measured the binding of FtsZ to ZipA incorporated in supported lipid bilayers at controlled densities by using a combination of biophysical surface-sensitive techniques (quartz crystal microbalance and spectroscopic ellipsometry) and analyzed how ZipA density and FtsZ concentration control the state of assembly of FtsZ. We found that ZipA attachment enables FtsZ-GMPCPP (where GMPCPP is a GTP analogue with a reduced level of hydrolysis) to assemble in several distinct ways: (i) two-dimensional polymerization at the membrane and (ii) three-dimensional polymerization from the membrane into the solution phase where this may be associated with the formation of higher-order complexes. In these processes, ZipA is required to enrich FtsZ at the surface but the FtsZ bulk concentration defines which morphology is being formed. Moreover, we report a strong effect of the nucleotide (GDP vs GMPCPP/GTP) on the kinetics of ZipA association/dissociation of FtsZ. These results provide insights into the mode of interaction of proto-ring elements in minimal membrane systems and contribute to the completion of our understanding of the initial events of bacterial division.


Contribution of the hydrophobic effect to globular protein stability.
The decrease in conformational stability, delta(delta G), has been measured for 72 aliphatic side-chain mutants from four proteins in which a larger side-chain is replaced by a smaller side-chain so that steric effects are minimal. When these delta(delta G) values are corrected to the same accessibility, namely 100% buried, then the following -delta(delta G) values per -CH2- group (in kcal/mol) are obtained: Ile----Val (1.26), Ala (1.26), Gly (1.26); Leu----Ala (1.16), Gly (1.21); Val----Ala (1.23), Gly (1.53). The average of these values is 1.27(+/- 0.07) kcal/mol. The 72 individual values range from 0 to 2.4 kcal/mol with an average value of 1.27(+/- 0.51) (standard deviation) kcal/mol. When the delta Gtr values from n-octanol to water are corrected for the difference in volume between the solutes and the solvents, the average value for the same substitutions is 1.25(+/- 0.05) kcal/mol. This suggests that proteins gain 1.3(+/- 0.5) kcal/mol in stability for each -CH2- group buried in folding, and, furthermore, that the volume corrected delta Gtr values for n-octanol for the amino acid side-chains provide good estimates of the contribution of the hydrophobic effect to globular protein stability.


Differences between the tolerance characteristics of two anticonvulsant benzodiazepines.
Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h.


Effects of inhaled metaproterenol and atropine on the pulmonary mechanics of infants with bronchopulmonary dysplasia.
We evaluated the individual and combined effects of an inhaled beta-adrenergic agent (metaproterenol) and an inhaled anticholinergic agent (atropine) on the pulmonary function of infants with bronchopulmonary dysplasia. In this randomized, double-blind study we studied 15 infants at a mean postnatal age of 15.8 weeks (range 4-28 weeks). On 4 successive days, pulmonary function tests were measured before and after a single treatment with one of the following four aerosols: placebo, metaproterenol, atropine, and combined metaproterenol and atropine. Following treatment with metaproterenol, atropine, and combined metaproterenol and atropine, airway resistance and maximal expiratory flow at functional residual capacity improved significantly when compared with baseline. Pulmonary function values returned toward baseline by 3 hours after the treatments. We found no significant differences between the effects of metaproterenol and atropine and were unable to show any synergy of the two agents.


Chlordiazepoxide effects on reactions to novelty and activity with and without prior drug experience.
Reactions to novelty, rearing and ambulation were observed in rats following saline or chlordiazepoxide injections either with or without prior drug experience. Drug suppression of the former two response was evident but there was no indication of prior drug experience being effective. However, experience appeared to negate the compound's depressant effect on ambulation shown by inexperienced subjects. It was concluded that inhibitory influences of chlordiazepoxide on reactions to novelty and rearing can not be ascribed to the aversive effects of a novel drug state.


Epidemiology of multiple sclerosis in Glasgow.
The objectives of the study were to establish the prevalence and incidence of multiple sclerosis in Glasgow and to assess the epidemiological importance of deprivation and ethnicity. The study was a descriptive cross-sectional study. Multiple sources of ascertainment were used to identify cases. The study was carried out in the population of three Local Health Care Cooperatives (LHCCs) in the area of Greater Glasgow NHS Board. The total population was approximately 169,000. In total, 245 patients with multiple sclerosis were identified. The mean age of patients was 49.8 years, the female to male ratio was 3.2:1, and the mean duration of disease was 16 years. The overall prevalence was 14.5 per 10,000, and the overall incidence 5.7 per 100,000 per year. Both the prevalence and incidence of multiple sclerosis were higher in the more affluent population. The crude prevalence in the Asian population was 6.3 per 20,000. The epidemiology of multiple sclerosis in Glasgow was similar, in most respects, to the epidemiology described in other parts of the U.K. There was evidence for the importance of deprivation as a determinant of both incidence and prevalence of disease. The reasons for the higher incidence and prevalence of multiple sclerosis in less deprived populations are not clear.


Physiological roles of mitochondrial fission in cultured cells and mouse development.
Mitochondria, which are double-membrane organelles thought to have originated through endosymbiosis of bacteria, play important roles in not only energy production, but also cellular signaling, differentiation, and development. The morphology of mitochondria is highly diverse among different tissues, and dynamic changes in mitochondrial morphology have been observed in response to various intracellular signals and stresses. These changes in mitochondrial morphology occur by repeated membrane fusion and fission events, which are regulated by three types of GTPase proteins: OPA1, Mfn1/2, Drp1 in mammalian cells. In recent years, the function and molecular mechanisms of mitochondrial dynamics have been demonstrated in cultured cells; however, the role of mitochondrial fission in maintaining tissue homeostasis remains poorly understood. Here, we review recent advances in research on the physiological role of mitochondrial fission in various differentiated tissue types in mammals.


The association between seven ERAP1 polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis involving 8,530 cases and 12,449 controls.
Besides the MHC gene, HLA-B27, ERAP1 is one of the non-MHC genes which also play key roles in the pathogenesis of AS. It has been reported that there is an association between ERAP1 polymorphisms and AS Risk. However, the results were inconclusive. The aim of the current study was to determine the contribution of ERAP1 polymorphisms to ankylosing spondylitis (AS) susceptibility. To derive a more precise estimation of the association, a meta-analysis was performed by searching the MEDLINE and EMBASE data base. The crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to access the strength of association between ERAP1 polymorphisms and AS risk. The pooled ORs were performed for minor allele versus major allele in all polymorphisms. Nine case-control studies consisting of 8,530 AS patients and 12,449 controls were identified in this meta-analysis. Except in rs27434 (P = 0.23), the significant correlation between ERAP1 polymorphisms and AS susceptibility has been detected in rs27044 (OR 1.57, P < 0.001), rs17482078 (OR 1.271, P < 0.001), rs10050860 (OR 0.772, P = 0.006), rs30187 (OR 1.348, P < 0.001), rs2287987 (OR 0.746, P < 0.001) and rs27037 (OR 1.257, P = 0.001). This meta-analysis demonstrates that the ERAP1 polymorphisms may play a significant role in susceptibility to AS. However, this result should be identified by more convincing experimental evidences in molecular level and population level.


Diabetes, a new mutation in the mouse.
Diabetes (db), which occurred in an inbred strain of mouse, is inherited as a unit autosomal recessive and is characterized by a metabolic disturbance resembling diabetes mellitus in man. Abnormal deposition of fat at 3 to 4 weeks of age is followed shortly by hyperglycemia, polyuria, and glycosuria. Accompanying morphological changes in the islets of Langerhans suggest neogenesis to compensate for insulin depletion.


Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive.
To determine the pharmacokinetic and pharmacodynamic interaction between oral tazarotene and an oral contraceptive containing norethindrone 1mg and ethinylestradiol 0.035 mg (Ortho-Novum 1/35). Two separate open-label, parallel-group, single-centre, pharmacokinetic and pharmacodynamic interaction studies. Twenty-seven healthy women (age 20-55 years) completed Study I, with a duration of 64 days during three consecutive menstrual cycles. Ortho-Novum 1/35 was taken once daily from study day 0 (first cycle day 1) to day 61 (third cycle day 6), and oral tazarotene 1.1 mg was coadministered daily from study day 34 (second cycle day 7) to day 61. Twenty-nine healthy women (age 20-44 years) completed Study II, with a duration of 75 days during three consecutive menstrual cycles. Ortho-Novum 1/35 was taken once daily from study day 0 (first cycle day 1) to day 74 (third cycle day 19), and oral tazarotene 6 mg was coadministered daily from study day 48 (second cycle day 21) to day 74. In both studies, the pharmacokinetics of tazarotenic acid on study day 61 (third cycle day 6) were evaluated from plasma tazarotenic acid concentrations. Pharmacokinetic parameters of plasma norethindrone and ethinylestradiol were compared before and after tazarotene administration (cycle day 6 of the second and third cycles, respectively). Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations were compared before and after tazarotene administration (cycle days 2, 4 and 6 of the second and third cycles, respectively). In Study II, serum progesterone concentrations were also determined on cycle days 18 and 20 of the second and third cycles. Tazarotenic acid was determined by liquid chromatography-tandem mass spectrometry. Ethinylestradiol and norethindrone were determined by gas chromatography-mass spectrometry. LH and FSH were assayed by microparticle enzyme immunoassay in Study I and by double-antibody radioimmunoassay in Study II. Progesterone was determined by solid-phase radioimmunoassay. In Study I (tazarotene 1.1 mg), the area under the plasma concentration-time curve from zero to 24 hours (AUC24) and the peak concentration in plasma (Cmax) for tazarotenic acid were 121 +/- 27 microg. h/L and 28.9 +/- 9.4 microg/L (mean +/- SD), respectively. In Study II (tazarotene 6 mg), AUC24 and Cmax for tazarotenic acid were 379 +/- 78 microg. h/L and 111 +/- 37 microg/L (mean +/- SD), respectively. In both studies, for both norethindrone and ethinylestradiol, the 90% CIs of AUC24 and Cmax on cycle day 6 before and after tazarotene administration were within the 80-125% boundary. In Study I, the 90% CIs of serum FSH and LH concentrations on cycle day 4 were within the 80-125% boundary. FSH and LH concentrations on cycle day 6 were marginally/partially outside the 80-125% boundary as a result of high variability. However, the mean FSH and LH serum concentrations on cycle day 6 of the third cycle were lower than those of the second cycle. In Study II, the 90% CIs of serum FSH, LH and progesterone concentrations were all within the 80-125% boundary, except for LH on cycle day 2. LH concentrations on cycle day 2 were marginally/partially outside the 80-125% boundary as a result of high variability. However, the mean serum LH concentration on cycle day 2 of the third cycle was lower than that of the second cycle. Oral tazarotene up to 6 mg once daily does not affect the pharmacokinetics and efficacy of Ortho-Novum 1/35.


Pretransplant risk factors and optimal timing for living-related liver transplantation in biliary atresia: experience of one Japanese children's hospital and transplantation center.
Although living-related liver transplantation (LRLT) is effective for patients with biliary atresia (BA) after a failed Kasai operation, the pretransplant factors affecting post-LRLT mortality and the optimal timing of the procedure remain unclear. A retrospective review of 27 patients with BA after a failed Kasai operation (median age, 22 months; range, 6-237 months) who received LRLT from 1994 to 2005 was done. The clinical characteristics at the time of the pre-LRLT assessment of those who did and did not survive were compared. A simple regression analysis and receiver operating characteristic analysis were done to correlate the clinical data. Among the 27 patients, 4 patients died within 1 year post-LRLT. The significant factors affecting posttransplant death were hepatopulmonary syndrome (HPS), age at LRLT, and graft-to-recipient weight ratio. The arterial blood gas analysis of HPS patients showed that there was a significant negative correlation between the SaO(2) value on room air and the intrapulmonary shunt ratio. The receiver operating characteristic analysis of age at LRLT showed that the optimal cutoff point was 103 months of age. Older children with HPS or a lower graft-to-recipient weight ratio are not ideal candidates for LRLT. The correlation between the shunt ratio and SaO(2) suggests that HPS could be detected early using pulse oximetry.


Gender affects reperfusion injury in rat liver.
Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdehyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldehyde and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.


[Normotest in the early neonatal period].
The aim of this study is the behavior of Normotest (NT) values in newborns in the first 4 days of life. The study has been carried out between January, 1982, and December, 1984, at the Department of Child Health and Neonatal Medicine - School of Medicine - University of Genoa. The number of infants tested was 1320. 694 were males and 626 females, 529 preterm (G.A. less than 37 weeks) and 791 full term babies. Infants have been tested from one to five times in the first four days of life, with the first evaluation within 12 hours of life. 1215 newborns (92%) presented NT values greater than 20%, 105 babies (8%) had NT below 20% in at least one evaluation, and received Vitamin K1 (0.5 mg/kg i.m.) as prophylaxis, being thereafter excluded from this study. Among the neonate with NT greater than 20%, 426 babies have been considered, who had, at least, three evaluations in the first four days of life. 288 (68%) of the 426 newborns, had not important disease, while 138 (32%) were sick neonates; of these babies 88 (64%) had respiratory distress syndrome and 50 (36%) had an infectious condition. The mean of NT values of the 426 newborns decreased from the first (33.84%) to the 2nd day (32.72%), with a following increment in 3rd (35.29%) and 4th day of life (39.01%). Newborns with gestational age (G.A.) less than 34 weeks showed significantly lower values than newborns with G.A. between 34-37 weeks and those with G.A. greater than 37 weeks. No newborn with NT values greater than 20% either received vitamin K or showed symptoms of haemorrhagic disease in early or later neonatal period.


The clinical benefit of epidermal growth factor receptor and human epidermal growth factor receptor 2 targeted agents adding to endocrine therapy in hormone receptor-positive breast cancer.
Studies have suggested that the crosstalk between estrogen receptor and ErbB receptor is involved in endocrine therapy (ET) resistance, which might be overcome by drugs-targeting ErbB receptor. However, the results of clinical studies remain controversial. The aim of this meta-analysis was to evaluate the efficacy and safety of ErbB (mainly epidermal growth factor receptor and human epidermal growth factor receptor 2 [HER2]) inhibitors added to ET for hormone receptor-positive breast cancer patients. Eligible randomized clinical trials on ET with or without ErbB receptor-targeting inhibitors (ERTI) for hormone receptor-positive breast cancer were identified by searching the main electronic databases (up to July 2015). Revman 5.3 was used to analyze the outcomes extracted from the included trials. In the overall population, ERTI failed to show any significant differences on overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). However, improvement on progression-free survival (PFS) (hazard ratio [HR] 0.84, 95% confidence interval [CI] = 0.76-0.93, P = 0.0005) was observed. For the HER2+ subgroup, ERTI could significantly improve ORR, CBR, PFS, OS, and time to progression compared to endocrine monotherapy. This improvement cannot be found in the HER2- subgroup. The risk of serious adverse events (SAEs) increased significantly when ERTI was present (RR = 2.09, 95% CI = 1.44-3.02, P < 0.0001). For HR+/HER2+ breast cancer, ERTI added to ET can significantly improve the clinical efficacy with the cost of increasing SAE.


MAP-kinase activity in etiolated Cucumis sativus cotyledons: the effect of red and far-red light irradiation.
Phytochrome (phy) signalling in plants may be transduced through protein phosphorylation. Mitogen-activated protein kinase (MAP-kinase, MAPK) activity and the effect of R (red) and FR (far-red) light irradiation on MAPK activity were studied in etiolated Cucumis sativus L. cotyledons. By in vitro protein phosphorylation and in-gel assays with myelin basic protein (MBP), a protein band (between 48 and 45 kDa) with MAPK-like activity was detected. The addition to the phosphorylation buffer of specific protein phosphatase (PTP) inhibitors (Na(3)VO(4) and NaF) and genistein, apigenin or PD98059 as MAPK inhibitors allowed us to confirm the MAPK activity of the protein band. Irradiation of etiolated cotyledons with FR light for 5, 10 or 60 min rapidly and transiently stimulated the MAPK activity of the protein band. This suggests that there was a very low fluence response (VLFR) of phys. In addition, 15 min of R light irradiation or a sequential treatment of 15 min of R plus 5 min of FR also increased MAPK activity. The stimulatory effect of R light was also attributed to the same photoreceptor, which suggests that MAPKs are involved in phytochrome signal transduction. Protein immunoprecipitation and immunoblotting analysis with the polyclonal antibody anti-pERK1/2 (Tyr 204) and the monoclonal antibody anti-phosphotyrosine PY20 allowed us to recognize the above mentioned protein band as two proteins with molecular masses (M(r)) of approximately 47 and 45 kDa, and MAPK activity. The biochemical and immunological properties showed by the proteins detected indicated that they were members of the MAPK family phosphorylated in tyrosine residues.


Alpha-naphthyl-acetate-esterase activity in cerebrospinal fluid cells.
Mono-histiocytes and T-lymphocytes were assessed by the cytochemical alpha-naphthyl-acetate-esterase (ANAE) stain in 50 CSF samples of patients with various neurological diseases. The ANAE-activity of lymphocytes was decreased in multiple sclerosis and subacute sclerosing panencephalitis, while the activity of mono-histiocytes was increased in the group of infarctions and bacterial and viral infections of the central nervous system. In bacterial meningitis and viral meningo-encephalo-radiculitis the number of ANAE-positive lymphocytes increased after treatment and clinical improvement. ANAE staining appears to be a useful additional tool in CSF cytology in these conditions.


Molecular cloning and tissue distribution of a novel marmoset ABC transporter.
Common marmosets (Callithrix jacchus) have been recognized as a useful small non-human primate model in preclinical testing for drug development. In this study, a cDNA of novel ATP-dependent efflux transporter ABCB1 was cloned from marmoset liver tissue. Marmoset ABCB1 cDNA encodes a protein of 1279 amino acid residues (MW = 141.4 kDa) containing characteristic regions of an ATP-binding cassette (ABC) protein, two hydrophobic transmembrane regions and two cytoplasmic nucleotide-binding regions, similar to human ABCB1. The deduced amino acid sequences were more highly identical (95%) to those of human ABCB1 compared with non-primate species such as dogs, pigs and rodents (79-90%). A close evolutionary relationship of ABCB1 among marmosets, cynomolgus and rhesus monkeys and humans was evident from a phylogenetic analysis using ABCB1 amino acid sequences from primates, dogs, pigs and rodents. Tissue distribution analyses by quantitative reverse transcription-polymerase chain reaction indicated that marmoset ABCB1 mRNA was most abundant in kidneys, followed by small intestines and livers, similar to human ABCB1, and marmoset ABCB1 proteins in these tissues were also detected by immunoblotting. These results indicated that the primary structure and tissue distribution of ABCB1 in marmosets were similar to those of humans, suggesting similar molecular characteristics of ABCB1 between marmosets and humans.


Early childhood growth patterns and school-age respiratory resistance, fractional exhaled nitric oxide and asthma.
Greater infant weight gain is associated with lower lung function and increased risk of childhood asthma. The role of early childhood peak growth patterns is unclear. We assessed the associations of individually derived early childhood peak growth patterns with respiratory resistance, fractional exhaled nitric oxide, wheezing patterns, and asthma until school-age. We performed a population-based prospective cohort study among 5364 children. Repeated growth measurements between 0 and 3 years of age were used to derive standard deviation scores (s.d.s) of peak height and weight velocities (PHV and PWV, respectively), and body mass index (BMI) and age at adiposity peak. Respiratory resistance and fractional exhaled nitric oxide were measured at 6 years of age. Wheezing patterns and asthma were prospectively assessed by annual questionnaires. We also assessed whether any association was explained by childhood weight status. Greater PHV was associated with lower respiratory resistance [Z-score (95% CI): -0.03 (-0.04, -0.01) per s.d.s increase] (n = 3382). Greater PWV and BMI at adiposity peak were associated with increased risks of early wheezing [relative risk ratio (95% CI): 1.11 (1.06, 1.16), 1.26 (1.11, 1.43), respectively] and persistent wheezing [relative risk ratio (95% CI): 1.09 (1.03, 1.16), 1.37 (1.17, 1.60), respectively] (n = 3189 and n = 3005, respectively). Childhood weight status partly explained these associations. No other associations were observed. PWV and BMI at adiposity peak are critical for lung developmental and risk of school-age wheezing. Follow-up studies at older ages are needed to elucidate whether these effects persist at later ages.


[Cognitive impairment and the risk of falling in the elderly].
Risk of fall is significantly increased in old people with cognitive decline due to specific associations between gait parameters and cognition. This association has recently been demonstrated, there being increasing evidence that cognitive domains such as attention, executive function and types of memory are critical for the correct regulation of gait. Gait disturbances can appear as early predictors of dementia in elderly patients. In the assessment of the fall risk, the use of dual tasks is novel, simple and relevant, especially in cognitive decline. Evidence for interventions in this population is limited, with vitamin D and physical exercise being the most encouraging, for decreasing the risk of fall in dementia.


The effect of activated charcoal on the absorption and elimination of astemizole.
1. The effect of activated charcoal on the absorption and elimination of astemizole and its metabolites was studied in healthy volunteers. 2. Subjects were divided into three groups containing seven subjects each. One group received 30 mg of astemizole with water only (control) and another group with 25 g of activated charcoal. The third group received multiple doses (12 g) of charcoal from 6 h onwards twice daily for 8 days. The concentrations of astemizole and its metabolites in plasma were measured by radioimmunoassay for 192 h. 3. Activated charcoal, administered immediately after astemizole ingestion, reduced the absorption of astemizole by 85% (P < 0.001). Multiple doses of activated charcoal, administered throughout the period of astemizole elimination, had no significant effect on the rate of elimination or the area under the curve from 0 to 192 h. 4. The absorption of astemizole from the gastrointestinal tract can be effectively prevented with activated charcoal. Because astemizole is rapidly absorbed, charcoal should be administered as soon as possible in acute astemizole poisoning. Multiple doses of charcoal do not seem to shorten the elimination half-life of astemizole.


F/Yb-codoped sol-gel silica glasses: toward tailoring the refractive index for the achievement of high-power fiber lasers.
Accurate control of both the doping distribution inside the fiber core and the low refractive index contrast between the fiber core and cladding materials is essential for the development of high-power fiber lasers based on the use of single-mode large-mode-area (LMA) optical fibers. Herein, sol-gel monolithic F/Yb3+-codoped silica glasses were prepared from porous large silica xerogels doped with ytterbium salt solution, which had been subjected to fluorination with hexafluoroethane gas, before subsequent sintering. The fluorine content inside the doped glass has been varied by adjusting the fluorination duration. The space homogeneity of fluorine and ytterbium concentrations in the cylindrical preforms has been checked by chemical analysis and Raman spectroscopy. Moreover, the glass with the lowest fluorine content has been successfully integrated as a core material in a microstructured optical fiber made using the stack-and-draw method. This fiber was tested in an all-fiber cavity laser architecture to evaluate potential lasing performances of the F/Yb3+-codoped silica glass. It presents a maximum efficiency of 70.4%, achieved at 1031 nm from a 1.16 m length fiber. These results confirm the potentialities of the obtained F/Yb3+-codoped glasses for the fabrication of LMA optical fiber lasers.


Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells.
This study is the first to investigate the anticancer effect of plumbagin in human breast cancer cells. Plumbagin exhibited cell proliferation inhibition by inducing cells to undergo G2-M arrest and autophagic cell death. Blockade of the cell cycle was associated with increased p21/WAF1 expression and Chk2 activation, and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C. Plumbagin also reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and the levels of inactivated phospho-Cdc2 and phospho-Cdc25C by Chk2 activation. Plumbagin triggered autophagic cell death but not predominantly apoptosis. Pretreatment of cells with autophagy inhibitor bafilomycin suppressed plumbagin-mediated cell death. We also found that plumbagin inhibited survival signaling through the phosphatidylinositol 3-kinase/AKT signaling pathway by blocking the activation of AKT and downstream targets, including the mammalian target of rapamycin, forkhead transcription factors, and glycogen synthase kinase 3beta. Phosphorylation of both of mammalian target of rapamycin downstream targets, p70 ribosomal protein S6 kinase and 4E-BP1, was also diminished. Overexpression of AKT by AKT cDNA transfection decreased plumbagin-mediated autophagic cell death, whereas reduction of AKT expression by small interfering RNA potentiated the effect of plumbagin, supporting the inhibition of AKT being beneficial to autophagy. Furthermore, suppression of AKT by plumbagin enhanced the activation of Chk2, resulting in increased inactive phosphorylation of Cdc25C and Cdc2. Further investigation revealed that plumbagin inhibition of cell growth was also evident in a nude mouse model. Taken together, these results imply a critical role for AKT inhibition in plumbagin-induced G2-M arrest and autophagy of human breast cancer cells.


Prevalence and cognitive impact of cerebrovascular findings in Alzheimer's disease: a retrospective, naturalistic study.
Cerebrovascular disease (CVD) is a major risk factor for cognitive decline associated with progression to Alzheimer's disease (AD) and dementia. The objective of this study was to retrospectively assess the prevalence of CVD and its cognitive impact in patients with AD in everyday clinical practice. Medical notes were retrospectively reviewed for all individuals who presented at East Sussex Memory Clinic (2004-2008) for investigation of cognitive impairment and had brain magnetic resonance imaging (MRI) as part of their clinical work-up. Global cognitive status was assessed with Mini-Mental State Examination (MMSE) and Cambridge Cognitive Examination. The extent of cerebrovascular abnormalities was qualitatively evaluated with MRI. Notes were reviewed for 232 patients (109 males, 123 females), mean age 76 years (range 62-93), who underwent MRI. Of these, 167 (72%) patients were diagnosed with AD. CVD was present in 89% of AD patients and 47% of patients had moderate to severe cerebrovascular abnormalities. The majority of patients (57%) had MMSE scores in the 21-26 range, indicative of mild AD. There was a trend towards worse cognitive status in patients with more severe CVD, which did not reach significance. Hachinski Ischaemic score indicated these patients did not have vascular dementia (VaD) (mean +/- standard deviation 1.1 +/- 1.3). These findings, based on qualitative MRI, indicate that cerebrovascular pathology is a very common associated feature in patients with mild to moderate AD, without VaD. Although the study suggests that CVD does not contribute to cognitive decline, and is not associated with the development of VaD, a non-significant trend was observed towards worsening cognitive status with increasing severity of CVD. The finding of this trend suggests a need for additional research, especially a prospective quantitative method of assessing CVD, to improve our understanding of how CVD contributes to cognitive impairment in AD.


Matrix metalloproteinases and their specific tissue inhibitors in menstruation.
The timely breakdown of extracellular matrix is essential for menstruation. Matrix metalloproteinases, which are able to degrade virtually all components of the extracellular matrix, are spatiotemporally expressed in the cyclic endometrium. The expression of most matrix metalloproteinases is regulated transcriptionally and their proteolytic activities are precisely controlled. The balance between matrix metalloproteinases and their specific tissue inhibitors is believed to be crucial for menstruation. This review focuses on the roles of matrix metalloproteinases and their tissue inhibitors in the initiation of menstruation and on the regulation of matrix metalloproteinase expression and activation. For example, the function of matrix metalloproteinases and their tissue inhibitors in endometrial re-epithelialization and angiogenesis during endometrial regeneration, when cell migration is facilitated to ensure endometrial repair, is discussed. This and other processes, although not fully resolved, serve to illustrate the involvement of matrix metalloproteinases and their tissue inhibitors in the process of menstruation.


Effects of aging on cell cooperation and lymphocyte responsiveness to cytokines.
Functional activities and cell cooperation of macrophages (Mphi), T cells, and B cells of young and old Lewis rats were compared. Splenic M phi from young and old rats provided accessory help for T cell mitogenesis and B cell mitogenesis, provided accessory help for generation of PFC, and produced IL 1 equally well as measured in costimulator assays. Splenic T cells of aged Lewis rats, however, were poorly responsive in mitogen assays and did not respond to supplemental IL 2 and antigen with blast transformation and with increased help for B cells to produce PFC. "Old" B cells did not respond in vitro to mitogens with help from M phi and T cells, nor did they respond to B cell helper factor with increased PFC. The data indicate that hyporesponsiveness of the immune system, especially of B cells, in aged rats is due in part to defective reactivity to interleukins and cytokine(s) and to defective cell-cell cooperation.


Seroprevalence of hepatitis B and factors potentially associated in a population-based study in Medellin, Colombia.
The seroprevalence of hepatitis B (HB) and of potentially associated factors in Medellin, Colombia, were investigated 17years after the start of universal vaccination. Biological and sociodemographic data from a population survey with a multistage random sampling were analyzed in 6-64year old individuals. HB surface antigen, total HB core antibodies and HB surface antibodies, and in some cases IgM antibodies to HB core antigen, were tested in 2077 samples. Factors potentially associated with and natural, and vaccine immunity relative to susceptibility (absence of any marker) were analyzed using a multinomial logistic regression. The prevalence of serological patterns was: chronic infection 0.20% (95% CI 0.11-0.71), vaccine immunity 25.10% (95% CI 21.72-28.83) and natural immunity 2.60% (95% CI 1.80-3.74). No markers were detected in 71.30% (95% CI 67.70-74.83) of the individuals and evidence of recent infection was not detected. Relative to the absence of markers, natural immunity was potentially associated with age (6-17years and 41-64years) and sleeping less than 6 hours, while vaccine immunity was associated with age (6-17years), reporting vaccination against HB, belonging to high socioeconomic strata, home ownership and being obese, after adjusting for other variables. These results may be a population effect of mass vaccination. It is recommended to complete the vaccination schedule and to study in detail, persistence of antibodies and the role of obesity and socioeconomic strata in the vaccine immunity.


Synthesis and biological properties of antiparallel and parallel dimers of alpha-human atrial natriuretic peptide.
To obtain antiparallel and parallel dimers of alpha-human atrial natriuretic peptide (alpha-hANP), two fully protected peptides I and II having the same amino acid sequence as alpha-hANP with different protective groups at the cysteinyl residues were synthesized, the former having Acm and Npys and the latter MeBzl and Acm. Equivalent amounts of peptides I and II were mixed and subjected to HF deprotection. Next, the first disulfide bond was linked between the remaining Npys group in I and the liberated SH group in II to form a monodisulfide dimer. The second disulfide bond was formed within the newly formed dimer between the remaining Acm groups by treatment with iodine, giving an antiparallel dimer. The parallel dimer of alpha-hANP was synthesized similarly starting from the protected peptide II. These dimers could be clearly segregated on HPLC. The retention time on HPLC of the antiparallel dimer was identical with that of natural beta-hANP. Both dimers showed biological activities as high as one third to one sixth of alpha-hANP in smooth muscle spasmolytic activity, and almost the same level of natriuretic activity as alpha-hANP at a high dose (10 nmol/kg) but about one fifth the activity at a low dose (1 nmol/kg). In these assay systems, the antiparallel dimer showed a slower onset and a tendency of longer duration than alpha-hANP.


Prevalence and risk-factors for Helicobacter pylori infection in urban and rural Beninese populations.
In total, 446 healthy individuals (240 in urban and 206 in rural environments, respectively) were selected from 96 households, based on cluster sampling of residential location. Demographic, sociological and environmental data were collected by face-to-face interviews using a standard questionnaire. Infection with Helicobacter pylori was assessed by detection of anti-H. pylori IgG serum antibodies. The prevalence of H. pylori antibodies was 75.4% in the urban population and 72.3% in rural (village) residents (p 0.459). No association was found between infection and age, gender, education level, size of household, economic activity or source of drinking water. The infection rate was higher in children whose parents were both infected, and also in children whose mother was infected (p < 0.001). By logistic regression analysis, the density of occupation of sleeping accommodation (more than three persons sharing a room; 95% odds ratio (OR) = 9.82 (4.13-23.31), p < 0.001), and the mother's status within the household (95% OR = 3.85 (1.53-9.67), p 0.003), were independent predictors for H. pylori infection. The 74% seroprevalence of H. pylori infection found in healthy Beninese individuals is similar to that reported previously from other parts of sub-Saharan Africa. Family contact with infected persons and crowded living conditions were associated with increased risk of infection. These findings are consistent with intra-familial H. pylori transmission and suggest that improvement of living conditions should be protective against infection.


Wandering Pattern Sensing at S-Band.
Increasing prevalence of dementia has posed several challenges for care-givers. Patients suffering from dementia often display wandering behavior due to boredom or memory loss. It is considered to be one of the challenging conditions to manage and understand. Traits of dementia patients can compromise their safety causing serious injuries. This paper presents investigation into the design and evaluation of wandering scenarios with patients suffering from dementia using an S-band sensing technique. This frequency band is the wireless channel commonly used to monitor and characterize different scenarios including random, lapping, and pacing movements in an indoor environment. Wandering patterns are characterized depending on the received amplitude and phase information of that measures the disturbance caused in the ideal radio signal. A secondary analysis using support vector machine is used to classify the three patterns. The results show that the proposed technique carries high classification accuracy up to 90% and has good potential for healthcare applications.


An immune dysregulation in MPN.
Myeloproliferative neoplasms (MPNs) are stem cell-derived clonal myeloid malignancies characterized by a unique somatic mutational profile since three mutually exclusive mutations (JAK2V617F, MPL, and CALR) sustain the great majority of the cases. However, clinical observation that autoimmune diseases may predispose to MPNs, autoimmune disorders or autoimmune phenomena may be associated with MPNs, and genetic constitutional variants that predispose to autoimmune disorders or inflammatory phenomena also predispose to MPNs raises a hypothesis that there might be an autoimmune/inflammatory basis underlying the pathogenesis of MPNs. Recent studies have documented that MPNs are characterized by an abnormal activity of key cells of the immune system, for example, increase in monocyte/macrophage compartment, altered regulatory T cell frequency, expansion of myeloid-derived suppressor cells, and CD4/natural killer cell dysfunction. This review is focused on summarizing recent advances in our understanding of immunological defects in MPNs with accompanying translational implications.


Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study.
Five European laboratories tested a simple in vitro batch system for dietary fibre fermentation studies. The inoculum was composed of fresh human faeces mixed with a carbonate-phosphate buffer complex supplemented with trace elements and urea. Five dietary fibre sources (cellulose, sugarbeet fibre, soyabean fibre, maize bran and pectin) were used by each laboratory on three occasions to determine pH, residual non-starch polysaccharides (NSP) and short-chain fatty acid production during fermentation. Cellulose and maize bran degradabilities were very low (7.2(SE 10.8) and 6.2 (SE 9.1)% respectively after 24 h), whereas pectin and soyabean fibre were highly degraded (97.4 (SE 4.4) and 91.1 (SE 3.4)% respectively after 24 h). Sugarbeet fibre exhibited an intermediate level of degradability (59.5 (SE 14.9)%). Short-chain fatty acid production was closely related to NSP degradation (r 0.99). Although each variable was ranked similarly by all laboratories, some differences occurred with respect to absolute values. However, the adaptation of donors to the experimental substrates was not an influential factor. Interlaboratory differences could be reduced either by adding less substrate during incubations or using less-diluted inocula. In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results. There was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat using the same fibres. The in vitro batch system tested during the present study provides a rapid means of obtaining quantitative estimates of the fermentation and the estimation of the energy content of new sources of dietary fibre.


pKa of 4MP and chemical equivalence in formulations of free base and salts of 4MP.
Fomepizole (4-Methylpyrazole, 4MP) is used as an antidote for ethylene glycol and methanol poisoning. In France it is administered intravenously as the sulfate or hydrochloride salt formulation and in the United States, as the free base formulation. Since its pKa was unknown, it was unknown if the free base, hydrochloride and sulfate salt formulations of 4MP are chemically equivalent, and if 4MP is in chemically equivalent forms in blood when these base and salt formulations are administered intravenously. Using UV spectrophotometry, the pKa of 4MP was determined to be 2.91 +/- 0.05 (n = 7) at a low concentration of 0.006 M in formate buffers of various pH, and 3.00 +/- 0.16 (n = 7) when high concentration of 4MP (0.06 M) was titrated with HCl at 25 degrees C. The hydrochloride salt formulation (pH 6.64) was ionically and hence chemically equivalent to the free base formulation (pH 7.02), while the sulfate salt formulation, due to its lower pH of 2.33, showed presence of some ionized 4MP indicating chemical inequivalence. In order to determine chemical equivalence upon intravenous administration, these formulations were diluted with phosphate buffer (pH 7.4) with identical ionic strength and buffer capacity as blood. In spite of chemical inequivalence of the sulfate salt formulation, 4MP free base was observed from all three formulations when diluted with physiological buffer suggesting chemical equivalence under physiological conditions due to the strong buffering action of blood.