Measurement of the axial vector form factor from antineutrino-proton scattering.

Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams1. The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon2. Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, FA, can be measured from neutrino scattering from free nucleons, νµn → µ-p and [Formula: see text], as a function of the negative four-momentum transfer squared (Q2). Up to now, FA(Q2) has been extracted from the bound nucleons in neutrino-deuterium scattering3-9, which requires uncertain nuclear corrections10. Here we report the first high-statistics measurement, to our knowledge, of the [Formula: see text] cross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA11 experiment, extracting FA from free proton targets and measuring the nucleon axial charge radius, rA, to be 0.73 ± 0.17 fm. The antineutrino-hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations12-15. Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments16-20 to better constrain neutrino interaction models.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection, and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms toward infected cells.

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective.

Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (182CWAIC186) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log10-fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.IMPORTANCE RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (182CWAIC186) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')2 form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.

12-Year within-wound study of the effectiveness of custom pressure garment therapy.

Pressure garment therapy is standard of care for prevention and treatment of hypertrophic scarring after burn injury. Nevertheless there is little objective data that confirms effectiveness. The purpose of this study was to determine the effectiveness of pressure garment therapy with objective data obtained with a randomized within-wound comparison. We enrolled consecutive patients with forearm injuries over a 12-year period. The subjects wore custom garments with normal and low compression randomized to either the proximal or distal zones. Hardness, color and thickness of wounds were objectively measured using appropriate devices; clinical appearance was measured by a panel masked to the identity of the pressure treated area. Wounds treated with normal compression were significantly softer, thinner, and had improved clinical appearance. There was no interaction of any effect with patient ethnicity. However, these findings were clinically evident only with moderate to severe scarring. We conclude that pressure garment therapy is effective, but that the clinical benefit is restricted to those patients with moderate or severe scarring.

Disturbed sleep and preterm birth: a potential relationship?

PURPOSE: Many women report disturbed sleep during pregnancy, but its impact on clinical outcomes remains unknown. This study examined subjective sleep quality and daytime sleepiness in relation to preterm birth. METHODS: A convenience sample of 220 pregnant women completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Perceived Stress Scale (PSS) during the second trimester. Women who had preterm and full-term births were compared on these measures. RESULTS: The preterm birth rate of the sample was 14.6%. Sleep latency, the period from lights out to sleep onset, was significantly longer in the preterm group, which also reported a tendency to use more sleep medications, but had lower PSQI daytime dysfunction scores. Perceived stress did not differentiate preterm and full-term groups. CONCLUSION: Disturbed sleep in pregnancy may be associated with preterm birth. Future studies should examine specific physiological factors that underlie this increased vulnerability.

SJL/J mice are highly susceptible to infection by mouse adenovirus type 1.

Mouse adenovirus type 1 (MAV-1) targets endothelial and monocyte/macrophage cells throughout the mouse. Depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. We surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (LD(50)s) were >10(4.4) PFU. However, SJL/J mice were highly susceptible to MAV-1, with a mean LD(50) of 10(-0.32) PFU. Infected C3H/HeJ (resistant) and SJL/J (susceptible) mice showed only modest differences in histopathology. Susceptible mice had significantly higher viral loads in the brain and spleen at 8 days postinfection than resistant mice. Infection of primary macrophages or mouse embryo fibroblasts from SJL/J and C3H/HeJ mice gave equivalent yields of virus, suggesting that a receptor difference between strains is not responsible for the susceptibility difference. When C3H/HeJ mice were subjected to sublethal doses of gamma irradiation, they became susceptible to MAV-1, with an LD(50) like that of SJL/J mice. Antiviral immunoglobulin G (IgG) levels were measured in susceptible and resistant mice infected by an early region 1A null mutant virus that is less virulent that wild-type virus. The antiviral IgG levels were high and similar in the two strains of mice. Taken together, these results suggest that immune response differences may in part account for differences in susceptibility to MAV-1 infection.

Disseminated Bipolaris spicifera in a neonate.

We report a premature infant with disseminated fungal infection identified as Bipolaris spicifera. The infant was born at 23 4/7 weeks' gestation, weighing 780 g. At day of life (DOL) 7 erythematous areas on the back were noticed that progressed to black, necrotic skin lesions. A shave biopsy showed invasive fungal organisms that were identified by culture as B. spicifera. The lesions progressed despite aggressive surgical debridement and antifungal therapy. On autopsy, fungal organisms found throughout the internal organs confirmed disseminated disease with B. spicifera. This organism is now more often recognized as a human pathogen; however, this is the first reported case in a neonate.

Diagnostic and operative transvaginal hydrolaparoscopy for infertility and pelvic pain.

STUDY OBJECTIVE: To review our experience with diagnostic and operative transvaginal hydrolaparoscopy (THL), a procedure that is less invasive than operative laparoscopy. DESIGN: Prospective, observational cohort study (Canadian Task Force classification II-2). SETTING: Private institute and university-affiliated hospital. PATIENTS: Twenty-nine women with infertility and 11 with pelvic pain. INTERVENTIONS: Diagnostic and operative THL. MEASUREMENTS AND MAIN RESULTS: Thirty-five (88%) diagnostic THLs were performed in the office and the other five were done in hospital for insurance reasons; all six operative THLs were performed in the office under conscious sedation. The procedure was conclusive (all organs seen) in 37 patients (93%). Based on THL, no further surgical intervention was recommended in 18 (62%) infertile women and 5 (45%) of those with pain. Further surgical intervention was required in 5 (56%) of 9 infertility patients with a previous normal hysterosalpingogram (HSG) and 6 (32%) of 19 infertility patients with no previous HSG. CONCLUSION: Transvaginal hydrolaparoscopy can be performed in the office with minimal pain, with a conclusive examination anticipated in 93% of cases. The procedure is more accurate than HSG and similar to laparoscopy.

GATA-4 and serum response factor regulate transcription of the muscle-specific carnitine palmitoyltransferase I beta in rat heart.

Transcriptional regulation of nuclear encoded mitochondrial proteins is dependent on nuclear transcription factors that act on genes encoding key components of mitochondrial transcription, replication, and heme biosynthetic machinery. Cellular factors that target expression of proteins to the heart have been well characterized with respect to excitation-contraction coupling. No information currently exists that examines whether parallel transcriptional mechanisms regulate nuclear encoded expression of heart-specific mitochondrial isoforms. The muscle CPT-Ibeta isoform in heart is a TATA-less gene that uses Sp-1 proteins to support basal expression. The rat cardiac fatty acid response element (-301/-289), previously characterized in the human gene, is responsive to oleic acid following serum deprivation. Deletion and mutational analysis of the 5'-flanking sequence of the carnitine palmitoyltransferase Ibeta (CPT-Ibeta) gene defines regulatory regions in the -391/+80 promoter luciferase construct. When deleted or mutated constructs were individually transfected into cardiac myocytes, CPT-I/luciferase reporter gene expression was significantly depressed at sites involving a putative MEF2 sequence downstream from the fatty acid response element and a cluster of heart-specific regulatory regions flanked by two Sp1 elements. Each site demonstrated binding to cardiac nuclear proteins and competition specificity (or supershifts) with oligonucleotides and antibodies. Individual expression vectors for Nkx2.5, serum response factor (SRF), and GATA4 enhanced CPT-I reporter gene expression 4-36-fold in CV-1 cells. Although cotransfection of Nkx and SRF produced additive luciferase expression, the combination of SRF and GATA-4 cotransfection resulted in synergistic activation of CPT-Ibeta. The results demonstrate that SRF and the tissue-restricted isoform, GATA-4, drive robust gene transcription of a mitochondrial protein highly expressed in heart.

Papers presented at the 8th international conference of maternity care researchers.

This column provides a brief overview of some of the papers and presentations offered at the 8th International Conference of Maternity Care Researchers, held September 2000 at the University of Glasgow in Scotland.

Adopting birth philosophies to guide successful birth practices and outcomes.

Research studies conducted recently in hospitals located in Switzerland and Canada reveal the importance of birth philosophies in attaining successful birth practices and outcomes.

Current research continues to support breastfeeding benefits.

Lamaze International and Lamaze Certified Childbirth Educators are strong supporters of breastfeeding. This paper reviews eight recent studies that are related to breastfeeding and useful to clinicians and educators.

Dexter: a tool to facilitate impairment ratings.

Calculating impairment in burn patients is crucial to understanding outcome. However, it is rarely reported after burns, presumably because the process of calculating impairment ratings is complicated and tedious. Computerized systems have been developed that facilitate the process, but it has not been established in burn patients that these systems reduce the time required to calculate impairment. We evaluated the Dexter Evaluation and Therapy System by Cedaron Medical Inc (Davis, CA). A sample of 10 manually recorded ratings was compared with 10 performed on the Dexter. Mean time for the manual technique was 65 +/- 35 minutes versus 37 +/- 13 minutes for the Dexter (P < .05, Mann-Whitney). The time taken to perform impairment ratings in burn survivors is significantly reduced by the use of the Dexter system. Time saving occurs primarily at three points: (1) electronic data entry directly from the measuring instruments, (2) compilation of data, and (3) rapid generation of reports.

Perinatal nursing research: a 25-year review--1976-2000.

Parent-infant nursing research from 1976-2000 is reviewed through four groups of studies: development of research instruments, studies of mothers and fathers through the childbearing years, studies of newborns (both healthy and at risk), and studies of special populations. Potential directions for maternal/parent/newborn nursing research in the 21st century are suggested.

Adolescent pregnancy rates in three European countries: lessons to be learned?

Adolescent pregnancy and abortion rates in the Netherlands, France, and Germany are lower than rates in the United States and the mean age of sexual debut is later. Contributing factors include philosophical differences about the rights and responsibilities of adolescents, access to contraceptives, sexuality education, and mass media campaigns. The data used in this article were gathered from meetings with health care providers in the three European countries studied and from published reports. While it is not possible to impose practices from one society upon another, nurses in North America may want to consider implementing some of these ideas in their practices.

Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance.

PURPOSE: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of 'induced radioresistance' (IRR). MATERIALS AND METHODS: Three cell lines, V79, RT112 and UM-UC-3, which are known to exhibit low-dose hypersensitivity (HRS) and induced radioresistance (IRR), and the radiosensitive cell line ATBIVA, were transfected with antisense oligonucleotides directed towards the DIR1 gene. Scrambled oligonucleotides were used as controls. DNA single-strand break (ssb) repair, using the alkaline comet assay, and cell survival using a standard clonogenic assay was measured after exposure to X-rays. RESULTS: Following treatment with 4Gy X-rays, the V79, RT112 and UM-UC-3 cell lines all exhibited significantly increased rates of ssb repair after transfection with DIR1 antisense oligonucleotides compared with cells transfected with scrambled oligonucleotides. They also demonstrated significantly enhanced survival after exposure to 2 Gy X-rays; the radiosensitive ATBIVA cells did not show these effects. CONCLUSIONS: Repression of the DIR1 gene product leads to an increase in the rate of repair and cell survival in three radioresistant cells lines but not in the radiosensitive ATBIVA cell line. Because DIR1 is repressed by X-rays in the dose range where IRR is observed, it may represent a candidate gene involved in the IRR phenomenon.

Cigarette smoking, low birth weight, and preterm births in low-income African American women.

OBJECTIVE: To examine effects of light and heavy cigarette smoking on the incidence of low birth weight (LBW) and preterm births in African American women. DESIGN: A total of 1146 low-income African American women participated in a randomized trial to test the effectiveness of nursing intervention in the reduction of preterm and LBW births. This secondary analysis focused on the effects of cigarette smoking on LBW (< 2500 gm) and preterm (< 37 weeks' gestation) births. RESULTS: Cigarette smoking had a significant effect on both LBW and preterm births. When light smokers were compared with nonsmokers, odds ratios were 1.89 (confidence interval (CI) 1.15, 3.13; p = 0.0127) for LBW births and 1.74 (CI 1.00; 3.02; p = 0.0499) for preterm births. When heavy smokers were compared with nonsmokers, odds ratios were 3.03 (CI 1.90, 4.86; p = 0.001) for LBW births and 2.60 (CI 1.55, 4.35; p = 0.0003) for preterm births. CONCLUSION: Cigarette smoking was associated with significantly higher rates of both LBW and preterm births in this sample of African American women.

Cost-benefit of a nursing telephone intervention to reduce preterm and low-birthweight births in an African American clinic population.

BACKGROUND: A cost-benefit analysis was performed to estimate the cost-savings obtained from a nursing telephone intervention delivered to pregnant women identified as being at risk for preterm or low-birthweight births. METHODS: After being screened for eligibility, a total of 1,554 women receiving prenatal care in a clinic located in Winston-Salem, North Carolina were randomized to intervention and control groups. Women in the intervention group received telephone calls from a registered nurse one or two times each week from the 24th through the 37th week of gestation. RESULTS: No clinical benefits were realized by Caucasian participants. The intervention reduced preterm and low-birthweight births, and resulted in cost savings, for African-American mothers ages 19 and over. No significant differences were seen in the rates of low-birthweight or preterm births and no cost savings were realized from intervention with women ages 18 and younger. CONCLUSIONS: A prenatal nursing support intervention in a clinic population of pregnant African American women was cost-beneficial for these adults (< or =19 years of age).

Ethical issues for nurses providing perinatal care in community settings.

Ethical issues in perinatal nursing are complex in that two patients--mother and fetus--are considered. This work considers six areas of potential ethical conflict: conflict between the mother and fetus, informed consent, confidentiality, cultural conflicts, conflicts associated with managed care, and conflicts in childbirth education. Ethical principles of autonomy, beneficence, and justice are included. Strategies for resolving ethical conflicts in community practice settings are suggested.