Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.

Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.

Human Milk Oligosaccharides in Colostrum and Mature Milk of Chinese Mothers: Lewis Positive Secretor Subgroups.

To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother's SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother's SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups as compared to the nonsecretor group. On the basis of the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided into two subgroups. HMOs that differed in level between Se+Le+ subgroups were 2'FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2'FL, LNT, and F-LNO as the driving force.

Multi-platform metabolomics analyses of a broad collection of fragrant and non-fragrant rice varieties reveals the high complexity of grain quality characteristics.

The quality of rice in terms not only of its nutritional value but also in terms of its aroma and flavour is becoming increasingly important in modern rice breeding where global targets are focused on both yield stability and grain quality. In the present paper we have exploited advanced, multi-platform metabolomics approaches to determine the biochemical differences in 31 rice varieties from a diverse range of genetic backgrounds and origin. All were grown under the specific local conditions for which they have been bred and all aspects of varietal identification and sample purity have been guaranteed by local experts from each country. Metabolomics analyses using 6 platforms have revealed the extent of biochemical differences (and similarities) between the chosen rice genotypes. Comparison of fragrant rice varieties showed a difference in the metabolic profiles of jasmine and basmati varieties. However with no consistent separation of the germplasm class. Storage of grains had a significant effect on the metabolome of both basmati and jasmine rice varieties but changes were different for the two rice types. This shows how metabolic changes may help prove a causal relationship with developing good quality in basmati rice or incurring quality loss in jasmine rice in aged grains. Such metabolomics approaches are leading to hypotheses on the potential links between grain quality attributes, biochemical composition and genotype in the context of breeding for improvement. With this knowledge we shall establish a stronger, evidence-based foundation upon which to build targeted strategies to support breeders in their quest for improved rice varieties.

Neonatal intensive care unit discharge of infants with cardiorespiratory events: Tri-country comparison of academic centers.

OBJECTIVE: Compare how NICUs within academic centers in Canada, France, and the United States make discharge decisions regarding cardiorespiratory recordings and home use of apnea monitors, oximeters and caffeine. STUDY DESIGN: An anonymous survey was sent to neonatologists through the member listserv of the American Academy of Pediatrics Section on Perinatal Pediatrics, the Canadian Fellowship Program Directory, and to Level 3 NICUs in France. RESULTS: The response rates were 89% , 83% , and 79% for US, Canada and France respectively. In Canada, 45% perform pre-discharge recordings vs. 38% in France and 24% in the US. Apnea free days prior to discharge were required in 100% of centers in Canada, 96% in France, and 92% in the US. In Canada and France, 65% and 68% of units discharge patients on monitors vs. 99% in the US. 64% of the US centers sometimes use home caffeine compared to 40% in Canada and 34% in France. Over 60% of the centers in Canada and France wait until at least 40 weeks post menstrual age to discharge patients, whereas only about 33% of the US wait that late to discharge patients. CONCLUSIONS: Discharge practices from NICUs are not well standardized across institutions or countries. Canada and France keep infants in the hospital longer and are less likely than the US to use home monitoring and home caffeine.

On the increase of predictive performance with high-level data fusion.

The combination of the different data sources for classification purposes, also called data fusion, can be done at different levels: low-level, i.e. concatenating data matrices, medium-level, i.e. concatenating data matrices after feature selection and high-level, i.e. combining model outputs. In this paper the predictive performance of high-level data fusion is investigated. Partial least squares is used on each of the data sets and dummy variables representing the classes are used as response variables. Based on the estimated responses y(j) for data set j and class k, a Gaussian distribution p(g(k)|y(j)) is fitted. A simulation study is performed that shows the theoretical performance of high-level data fusion for two classes and two data sets. Within group correlations of the predicted responses of the two models and differences between the predictive ability of each of the separate models and the fused models are studied. Results show that the error rate is always less than or equal to the best performing subset and can theoretically approach zero. Negative within group correlations always improve the predictive performance. However, if the data sets have a joint basis, as with metabolomics data, this is not likely to happen. For equally performing individual classifiers the best results are expected for small within group correlations. Fusion of a non-predictive classifier with a classifier that exhibits discriminative ability lead to increased predictive performance if the within group correlations are strong. An example with real life data shows the applicability of the simulation results.

Evaluation of the impact of direct plating, broth enrichment, and specimen source on recovery and diversity of methicillin-resistant Staphylococcus aureus isolates among HIV-infected outpatients.

We compared recovery of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) from nasal and groin swab specimens of 600 HIV-infected outpatients by selective and nonselective direct plating and broth enrichment. Swabs were collected at baseline, 6-month, and 12-month visits and cultured by direct plating to mannitol salt agar (MSA) and CHROMagar MRSA (CM) and overnight broth enrichment with subculture to MSA (broth). MRSA isolates were characterized by pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome mec (SCCmec) typing, and PCR for the Panton-Valentine leukocidin. At each visit, 13 to 15% of patients were colonized with MRSA and 30 to 33% were colonized with methicillin-susceptible S. aureus (MSSA). Broth, CM, and MSA detected 95%, 82%, and 76% of MRSA-positive specimens, respectively. MRSA recovery was significantly higher from broth than CM (P ≤ 0.001) or MSA (P ≤ 0.001); there was no significant difference in recovery between MSA and CM. MSSA recovery also increased significantly when using broth than when using MSA (P ≤ 0.001). Among specimens collected from the groin, broth, CM, and MSA detected 88%, 54%, and 49% of the MRSA-positive isolates, respectively. Broth enrichment had a greater impact on recovery of MRSA from the groin than from the nose compared to both CM (P ≤ 0.001) and MSA (P ≤ 0.001). Overall, 19% of MRSA-colonized patients would have been missed with nasal swab specimen culture only. USA500/Iberian and USA300 were the most common MRSA strains recovered, and USA300 was more likely than other strain types to be recovered from the groin than from the nose (P = 0.05).

Methicillin-resistant Staphylococcus aureus colonization in HIV-infected outpatients is common and detection is enhanced by groin culture.

SUMMARYAlthough high rates of clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in HIV-infected adults, data on MRSA colonization are limited. We enrolled HIV-infected adults receiving care at the Atlanta VA Medical Center. Swabs from each participant's nares and groin were cultured with broth enrichment for S. aureus. Of 600 HIV-infected adults, 79 (13%) were colonized with MRSA and 180 (30%) with methicillin-susceptible S. aureus. MRSA pulsed-field gel electrophoresis types USA300 (n=44, 54%) and USA500/Iberian (n=29, 35%) predominated. Inclusion of groin swabs increased MRSA detection by 24% and USA300 detection by 38%. In multivariate analysis, MRSA colonization compared to no MRSA colonization was associated with a history of MRSA clinical infection, rarely or never using condoms, and contact with prisons and jails. In summary, the prevalence of MRSA colonization was high in this study of HIV-infected adults and detection of USA300 was enhanced by groin culture.

Staphylococcus aureus community-onset pneumonia in patients admitted to children's hospitals during autumn and winter of 2006-2007.

Staphylococcus aureus is a relatively uncommon cause of community-onset pneumonia (COP) that may complicate influenza infection. We reviewed admissions to children's hospitals to describe more systematically this entity. Records of patients hospitalized at three children's hospitals between 1 October 2006 and 30 April 2007 who had a positive S. aureus culture from a sterile site or respiratory specimen were reviewed and data were abstracted for episodes of primary S. aureus COP. Overall, 30 episodes met criteria for primary S. aureus COP; 12 (41%) involved methicillin-resistant S. aureus. Patients in 11 (37%) episodes were seen by a healthcare provider for their symptoms prior to hospital admission; three received an antimicrobial, none of which had activity against the S. aureus isolated. Mechanical ventilation was required in 21 (70%) episodes; five (17%) patients died. When evaluating patients with severe COP, providers should be aware of the potential for S. aureus, including methicillin-resistant strains.

Methicillin-resistant Staphylococcus aureus infections among healthy full-term newborns.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged in the community, causing disease among healthy people lacking traditional risk factors for MRSA infection. This article describes an outbreak of MRSA among healthy full-term newborns. DESIGN: Cases were identified and corresponding medical information collected. Telephone interviews were conducted with mothers of cases and surveillance cultures from mothers and newborns were performed. MRSA isolates were genotyped. SETTING: Hospital in Chicago, Illinois, USA. PARTICIPANTS: Newborns, their mothers and hospital healthcare workers. INTERVENTION: Nursery infection control practices were enhanced. The MRSA-colonised healthcare workers received intranasal mupirocin. MAIN OUTCOME: Within 4-23 days of birth, 11 newborns were identified with pustules, vesicles or blisters located on the head, groin, perineum, ears, legs, chin and trunk. All received antimicrobials and recovered without incident. RESULTS: None of 432 peripartum women, one of 399 newborns, and two of 135 healthcare workers were nasal MRSA carriers. Available isolates from six patients, two healthcare workers, and one from an MRSA-colonised newborn were similar by pulsed-field gel electrophoresis. Other than contact with the hospital, no common exposures of MRSA transmission were identified. CONCLUSIONS: MRSA strains that initially emerged in the community are now causing disease in healthcare settings. Providers should be aware that MRSA can cause skin infections among healthy newborns. Adherence to standard infection control practices is important to prevent transmission of MRSA in nurseries.

Powder pattern indexing using the weighted crosscorrelation and genetic algorithms.

X-ray diffraction is a powerful technique for investigating the structure of crystals and crystalline powders. Unfortunately, for powders, the first step in the structure elucidation process, retrieving the unit cell parameters (indexing), is still very critical. In the present article, an improved approach to powder pattern indexing is presented. The proposed method matches peak positions from experimental X-ray powder patterns with peak positions from trial cells using a recently published method for pattern comparison (weighted crosscorrelation). Trial cells are optimized with Genetic Algorithms. Patterns are not pretreated to remove any existing zero point shift, as this is determined during optimization. Another improvement is the peak assignment procedure. This assignment is needed for determining the similarity between lines from trial cells and experiment. It no longer allows calculated peaks to be assigned twice to different experimental peaks, which is beneficial for the indexing process. The procedure proves to be robust with respect to false peaks and accidental or systematic absensences of reflections, and is successfully applied to powder patterns originating from orthorhombic, monoclinic, and triclinic compounds measured with synchrotron as well as with conventional laboratory X-ray diffractometers.

Vancomycin-intermediate Staphylococcus aureus in a home health-care patient.

In June 2000, vancomycin-intermediate Staphylococcus aureus (VISA) was isolated from a 27-year-old home health-care patient following a complicated cholecystectomy. Two VISA strains were identified with identical MICs to all antimicrobials tested except oxacillin and with closely related pulsed-field gel electrophoresis types. The patient was treated successfully with antimicrobial therapy, biliary drainage, and reconstruction. Standard precautions in the home health setting appear successful in preventing transmission.

Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity.

A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent as trolox), but in the LPO assay IC(50) values ranged from 0.2 to 37 microM. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents.

Evaluation of the Vitek 2 system for susceptibility testing of Streptococcus pneumoniae isolates.

Vitek 2 (bioMérieux, France) is a new commercial system that allows rapid identification and rapid determination of the minimum inhibitory concentration (MIC) of Streptococcus pneumoniae by monitoring the growth kinetics of the organisms in microwells. The accuracy of the Vitek 2 system in susceptibility testing was evaluated by determining the MICs of 50 penicillin-susceptible and 150 intermediate or penicillin-resistant Streptococcus pneumoniae isolates and comparing the results with those obtained using the agar dilution method. The essential agreement between the Vitek 2 system and the reference method was 91% for penicillin, 93% for cefotaxime and ceftriaxone, and more than 94% for amoxicillin, erythromycin, ofloxacin, co-trimoxazole, tetracycline, and imipenem. One very major error (1.1%) and one major error (0.9%) were obtained for tetracycline. The minor error rate for penicillin of 19.3% was mainly due to intermediate category isolates (n = 29) being identified as resistant and susceptible isolates (n = 6) being identified as intermediate by the commercial system. The minor error rates for amoxicillin, cefotaxime, ceftriaxone, imipenem, and ofloxacin were 25.4%, 25.4%, 29.4%, 19.2%, and 31.5%, respectively. Vancomycin, tetracycline, co-trimoxazole, and erythromycin showed minor error rates of 0-6.1%. In conclusion, Vitek 2 shows good agreement with the reference method, as demonstrated by the low numbers of major errors, but it has a tendency to overestimate MICs, resulting in minor errors.

Cryptic translocation t(5;18) in familial mental retardation.

A cryptic translocation t(5;18)(qter;qter) was detected in a large family, using a FISH-based approach combining subtelomeric probes to allow the subtelomeric regions of most chromosome ends to be analysed for deletions and balanced or unbalanced translocations. Unbalanced karyotypes (duplication 5qter/deficiency 18qter) resulted in a previously undescribed association of moderate to severe mental retardation, microcephaly, pre- and postnatal growth retardation, distinct facial dysmorphism, narrow auditory canals, genital hypoplasia, left heart hypoplasia in one patient and severe behaviour difficulties in another. Some of the features observed in affected individuals are characteristic of known syndromes involving either 18q (growth deficiency, nystagmus, narrow auditory canals, genital hypoplasia, behaviour problems in 18q deletion syndrome) or 5q (umbilical and inguinal hernias, congenital heart defects in distal 5q trisomy).

Immunocytochemical localization of a calmodulinlike protein in Bacillus subtilis cells.

To determine possible functions of the calmodulinlike protein of Bacillus subtilis, the time course of its expression during sporulation and its cellular localization were studied. The protein was expressed in a constitutive manner from the end of logarithmic growth through 8 h of sporulation as determined by antibody cross-reactivity immunoblots and enzyme-linked immunosorbent assays (ELISAs). In partially purified extracts, the immunopositive protein comigrated upon electrophoresis with a protein which selectively bound [(45)Ca]CaCl(2), ruthenium red, and Stains-all. Previous studies showed increased extractability of the calmodulinlike protein from B. subtilis cells when urea and 2-mercaptoethanol were used in breakage buffers, implying that the protein might be partially associated with the membrane fraction. This was confirmed by demonstrating that isolated membrane vesicles of B. subtilis also gave positive immunological tests with Western blotting and ELISAs. To more precisely locate the protein in cells, thin sections of late-log-phase cells, sporulating cells, and free spores were reacted first with bovine brain anticalmodulin specific antibodies and then with gold-conjugated secondary antibodies; the thin sections were examined by transmission electron microscopy. The calmodulinlike protein was found almost exclusively associated with the cell envelope of these fixed, sectioned cells. A possible function of the calmodulinlike protein in sensing calcium ions or regulating calcium ion transport is suggested.

Congenital and perinatal tuberculosis: discussion of difficult issues in diagnosis and management.

Tuberculosis (TB) has become more prevalent in women of childbearing age and, as well, more frequent in their children. This has occurred for a number of reasons, including: (1) women and children who have immigrated to this country from areas where TB is endemic, such as Mexico and Southeast Asia; (2) the development of multidrug-resistant organisms; (3) the increase seen in patients who live in congregate areas who are at higher risk for acquisition of TB; (4) more difficult access to adequate medical care; and (5) increases in adults and children who have become infected with human immunodeficiency virus. The focus of this review is on congenital and perinatally acquired TB including discussion of epidemiology, the stages of TB, the effects of TB infection and disease during pregnancy on the fetus and mother, congenital and perinatal TB, the potential role of the use of BCG vaccine in infants, and the emergence of multidrug-resistant TB on therapy of the pregnant mother and her fetus and the mother and her infant after delivery.

Neonatal cardiopulmonary resuscitation: the good news and the bad.

Many health care professionals all over the world have been taught neonatal cardiopulmonary resuscitation (CPR) using the neonatal CPR course based upon the work of Bloom and Cropley. The purpose of this article is to provide a retrospective review of the development of some of the neonatal CPR techniques, to discuss current techniques and to complement the dedication of this issue to Dr. Ronald Brown and Catherine Copley, MN, RN.