Increasing facility delivery through maternity waiting homes for women living far from a health facility in rural Zambia: a quasi-experimental study.

OBJECTIVE: To report on the effectiveness of a standardised core Maternity Waiting Home (MWH) model to increase facility deliveries among women living >10 km from a health facility. DESIGN: Quasi-experimental design with partial randomisation at the cluster level. SETTING: Seven rural districts in Zambia. POPULATION: Women delivering at 40 health facilities between June 2016 and August 2018. METHODS: Twenty intervention and 20 comparison sites were used to test whether MWHs increased facility delivery for women living in rural Zambia. Difference-in-differences (DID) methodology was used to examine the effectiveness of the core MWH model on our identified outcomes. MAIN OUTCOME MEASURES: Differences in the change from baseline to study period in the percentage of women living >10 km from a health facility who: (1) delivered at the health facility, (2) attended a postnatal care (PNC) visit and (3) were referred to a higher-level health facility between intervention and comparison group. RESULTS: We detected a significant difference in the percentage of deliveries at intervention facilities with the core MWH model for all women living >10 km away (DID 4.2%, 95% CI 0.6-7.6, P = 0.03), adolescent women (<18 years) living >10 km away (DID 18.1%, 95% CI 6.3-29.8, P = 0.002) and primigravida women living >10 km away (DID 9.3%, 95% CI 2.4-16.4, P = 0.01) and for women attending the first PNC visit (DID 17.8%, 95% CI 7.7-28, P < 0.001). CONCLUSION: The core MWH model was successful in increasing rates of facility delivery for women living >10 km from a healthcare facility, including adolescent women and primigravidas and attendance at the first PNC visit. TWEETABLE ABSTRACT: A core MWH model increased facility delivery for women living >10 km from a health facility including adolescents and primigravidas in Zambia.

Efficacy of a Comprehensive Dysphagia Intervention Program Tailored for the Residents of Nursing Homes.

Oropharyngeal dysphagia is a widespread condition in older people and thus poses a serious health threat to the residents of nursing homes. The management of dysphagia relies mainly on compensatory strategies, such as diet and environmental modification. This study investigated the efficacy of an intervention program using a single-arm interventional study design. Twenty-two participants from nursing homes were included and had an average of 26 hours of intervention, including oromotor exercises, orosensory stimulation and exercises to target dysphagia and caregiver training. Four of the 22 participants exhibited improvement in functional oral intake scale (FOIS) but was not statistically significant as a group. All oromotor function parameters, including the range, strength, and coordination of movements, significantly improved. These results indicate that this intervention program could potentially improve the oromotor function, which were translated into functional improvements in some participants' recommended diets. The validity of this study could be improved further by using standardized swallowing and feeding assessment methods or an instrumental swallowing assessment.

Caesarean birth and risk of subsequent preterm birth: a retrospective cohort study.

OBJECTIVE: To determine the risk of spontaneous and medically indicated preterm birth associated with mode of birth in previous term-born pregnancy. DESIGN: Retrospective cohort study. SETTING: Two UK maternity units. POPULATION OR SAMPLE: A total of 16 340 women with first two consecutive singleton births and the first birth at term. METHODS: Retrospective cohort study using routinely collected clinical data. MAIN OUTCOME MEASURES: Incidence of spontaneous preterm birth and medically indicated preterm birth at less than 37 weeks of gestation after term birth, in relation to mode of birth in first pregnancy. Subgroup analysis on cervical dilatation at the time of first caesarean birth. RESULTS: Compared with vaginal birth, emergency caesarean birth at full dilatation was associated with an increase in spontaneous preterm birth (2.3% vaginal birth versus 4.5% full dilatation caesarean; adjusted odds ratio [aOR] 3.29, 95% CI 2.02-5.13, P < 0.001). Elective caesarean, emergency caesarean at <4 cm dilatation, and emergency caesarean at 4-9 cm dilatation were associated with increased medically indicated preterm birth (0.8% vaginal births versus 1.9% elective caesarean, 3.3% <4 cm caesarean, 1.3% 4-9 cm caesarean; aOR 2.30, 95% CI 1.19-4.15, P = 0.009; aOR 4.68, 95% CI 2.98-7.24, P < 0.001; and aOR 2.43, 95% CI 1.43-4.00, P = 0.001, respectively). CONCLUSIONS: Term caesarean in the first stage of labour or performed prelabour is associated with medically indicated preterm birth. Term caesarean in the second stage of labour is associated with spontaneous preterm birth. TWEETABLE ABSTRACT: Caesarean in the second stage of labour is associated with spontaneous preterm birth.

Characterization and application studies of ProxyPhos, a chemosensor for the detection of proximally phosphorylated peptides and proteins in aqueous solutions.

Proximal phosphorylation on proteins appears to have functional significance and has been associated with several diseases, including Alzheimer's and cancer. While much remains to be learned about the role of proximal phosphorylation in biological systems, no simple and/or affordable technique is available for its detection. To this end, we have previously developed a ProxyPhos chemosensor, which detects proximally phosphorylated peptides and proteins over mono- and non-phosphorylated motifs in aqueous solutions. In this follow-up work, we performed extensive characterization of peptide and protein ProxyPhos assay conditions to achieve enhanced detection, and further explored the selectivity of ProxyPhos, and its potential off-targets. As a result of characterization studies, selective sensing of proximally phosphorylated over mono-phosphorylated peptides and proteins was achieved. Moreover, studies demonstrated that ProxyPhos was compatible with the detection of all commonly phosphorylated residues (i.e. tyrosine, serine and threonine residues). Under optimized conditions, ProxyPhos efficiently discriminated between peptides derived from the activated (proximally phosphorylated, disease-relevant) and inactive (mono-phosphorylated) forms of JAK2, SYK and MAPK1 kinases. In addition, ProxyPhos can be used to probe phosphatase activity on peptides and proteins via detecting changes in proximal phosphorylation, demonstrating immediate utility of this chemosensing system.

Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore.

This retrospective case-control study was undertaken to review the clinical features associated with heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections and the local impact they have on clinical outcome. Compared with vancomycin-susceptible S. aureus (n = 30), hVISA and VISA infections (n = 10) are found to be associated with a longer period of prior glycopeptide use (P = 0.01), bone/joint (P < 0.01) and prosthetic infections (P = 0.04), as well as treatment failure, as evidenced by longer bacteremic (P < 0.01) and culture positivity (P < 0.01) periods. This was observed to have resulted in longer hospital length of stay (P < 0.01) and total antibiotic therapy duration (P = 0.01). There was, however, no significant difference in the overall patient mortality or the hospitalization cost (P = 0.12) in both groups. Clinicians should be cognizant of the association between hVISA/VISA with high bacterial load deep-seated infections. We recommend targeted and even universal screening for hVISA/VISA in methicillin-resistant S. aureus (MRSA) infections.

Nutrigenomics, beta-cell function and type 2 diabetes.

INTRODUCTION: The present investigation was designed to investigate the accuracy and precision of lactate measurement obtained with contemporary biosensors (Chiron Diagnostics, Nova Biomedical) and standard enzymatic photometric procedures (Sigma Diagnostics, Abbott Laboratories, Analyticon). MATERIALS AND METHODS: Measurements were performed in vitro before and after the stepwise addition of 1 molar sodium lactate solution to samples of fresh frozen plasma to systematically achieve lactate concentrations of up to 20 mmol/l. RESULTS: Precision of the methods investigated varied between 1% and 7%, accuracy ranged between 2% and -33% with the variability being lowest in the Sigma photometric procedure (6%) and more than 13% in both biosensor methods. CONCLUSION: Biosensors for lactate measurement provide adequate accuracy in mean with the limitation of highly variable results. A true lactate value of 6 mmol/l was found to be presented between 4.4 and 7.6 mmol/l or even with higher difference. Biosensors and standard enzymatic photometric procedures are only limited comparable because the differences between paired determinations presented to be several mmol. The advantage of biosensors is the complete lack of preanalytical sample preparation which appeared to be the major limitation of standard photometry methods.

Synthetic approaches to a variety of covalently linked porphyrin--fullerene hybrids.

There is substantial interest in dyads in which C(60) is covalently linked to electron donors, such as porphyrins, which absorb light strongly in the visible region. We present here the details of the syntheses of such compounds, which can be broadly organized into categories depending upon the nature of the linker joining the two chromophores. The structural aspects of intramolecular electronic interaction that we have sought to explore have dictated the synthetic strategies employed to generate these classes of molecules. Flexible glycol linkers were used to allow close approach between the fullerene and porphyrin, facilitating through-space interactions. These linkers also allowed studies of the effects of metal cation complexation. Naphthalene and alkyne linkers were used to examine the possible effects a conjugated or aromatic linker might have on photophysical properties. Finally, steroids were used as linkers in dyads expected to possess a large distance between the two chromophores, in which only through-bond interactions between the fullerene and porphyrin should be possible.

Size-dependent control of the binding of biotinylated proteins to streptavidin using a polymer shield.

Many medical and biotechnological processes rely on controlling and manipulating the molecular-recognition capabilities of proteins. This can be achieved using small molecules capable of competing for protein binding or by changing environmental parameters that affect protein structure and hence binding. An alternative is provided by stimuli-responsive polymers that change reversibly from a water-soluble expanded coil to a water-insoluble collapsed globule upon small changes in temperature, pH or light intensity: when attached to proteins in the vicinity of their binding sites, they reversibly block and release small ligands. Here we show how this approach can be extended to achieve size-selective binding of large, macromolecular ligands. We use the thermally responsive polymer poly(N,N-diethylacrylamide) (PDEAAm), and attach it to the protein streptavidin approximately 20 A from the binding site for biotinylated proteins. Below the lower critical solution temperature of PDEAAm, the polymer is in its extended state and acts as a 'shield' to block the binding of large biotinylated proteins; above this temperature, it collapses and exposes the binding site, thereby allowing binding. We find that the degree of shielding depends on both the size of the biotinylated protein and the size of PDEAAm, suggesting that 'smart' polymer shields could be tailored to achieve a wide range of size-dependent ligand discrimination for use in affinity separations, biosensors and diagnostics technologies.

Founder's Award, Society for Biomaterials. Sixth World Biomaterials Congress 2000, Kamuela, HI,May 15-20, 2000. Really smart bioconjugates of smart polymers and receptor proteins.

Over the past 18 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. This article summarizes our work with one of these conjugate systems, specifically polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally sensitive random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.

A clinic and community-based approach to hypertension control for an underserved minority population: design and methods.

This paper describes the design and methodology of the Community Hypertension Intervention Project (CHIP). CHIP is investigating the environmental and psychosocial factors related to treatment adherence and examining the effects of combining usual hypertension care with the effects of three interventions designed to improve patient compliance with treatment for high blood pressure in a high-risk, underserved minority population. Thirteen hundred and sixty-seven inner-city hypertension patients (75% black and 25% Hispanic) have agreed to participate in the 4-year longitudinal study. These participants were randomized to usual care or one of three intervention groups: individualized counseling sessions; home visits/discussion groups; or computerized appointment-tracking system. Participants are representative of the surrounding, predominantly low-income minority community and are treated in a hospital-based clinic and in a private clinic in the community. About 65% have blood pressure levels considered to be out of control. It was concluded that structural changes at the clinic site, along with the targeted interventions, would improve patient satisfaction, increase treatment adherence, and improve blood pressure control.

Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders.

This study examined whether adolescents with major depressive disorder (MDD) display the abnormal electroencephalographic (EEG) alpha asymmetries found in depressed adults. Resting EEG was recorded in 25 right-handed female outpatients (19 with MDD, 11 of whom also had a current anxiety disorder; 6 with anxiety disorders only) and 10 non-ill controls. In contrast to the non-ill controls, adolescents having MDD but no anxiety disorder showed alpha asymmetry indicative of less activation over right than over left posterior sites. Within the MDD patient group, comorbid anxiety disorders reduced the posterior alpha asymmetry, supporting the potential importance of evaluating anxiety in studies of regional brain activation in adolescent MDD. These preliminary findings are similar to those from adult studies that suggest that MDD is associated with right parietotemporal hypoactivation.

Thermoprecipitation of streptavidin via oligonucleotide-mediated self-assembly with poly(N-isopropylacrylamide).

A versatile strategy has been developed for selectively and sequentially isolating targets in a liquid-phase affinity separation environment. The strategy uses a recently developed approach for joining together molecules in linkages that are defined by the complementary pairing of oligonucleotides conjugated to the different molecules [Niemeyer, C. M., Sano, T., Smith, C. L., and Cantor, C. R. (1994) Nucleic Acids Res. 22, 5530-9]. In the work presented here, streptavidin was noncovalently coupled with the temperature-responsive poly(N-isopropylacrylamide) [poly(NIPAAM)] through the sequence-specific hybridization of oligonucleotides conjugated to the protein and polymer. A 20-mer oligonucleotide was covalently linked through a heterobifunctional linker to a genetically engineered streptavidin variant that contained a unique cysteine residue at the solvent-accessible site Glu 116. The complementary DNA sequence was conjugated to the end of a linear ester-activated poly(NIPAAM). The two conjugates were allowed to self-assemble in solution via hybridization of their complementary DNA sequences. The streptavidin-poly(NIPAAM) complex could be used to affinity-precipitate radiolabeled biotin or biotinylated alkaline phosphatase above 32 degrees C through the thermally induced phase separation activity of the poly(NIPAAM). The streptavidin-oligo species could then be reversibly separated from the precipitated polymer-oligo conjugate and recycled by lowering the salt concentration, which results in denaturation of the short double-stranded DNA connection. The use of oligonucleotides to couple polymer to streptavidin allows for selective precipitation of different polymers and streptavidin complexes based on the sequence-specific hybridization of their oligonucleotide appendages.

The human secretin receptor gene: genomic organization and promoter characterization.

Secretin is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. In this report, the organization of the human secretin receptor (hSR) gene was characterized by overlapping genomic phage clones. The hSR gene consists of 13 exons and 12 introns with all the splice donor and acceptor sites conforming to the canonical GT/AG rule. By transient reporter gene assays, the wild-type promoter, containing 3.0 kb of the hSR gene 5' flanking region, was able to drive 5.8 +/- 0.6 and 6.6 +/- 0.2-fold (P < 0.01) increases in luciferase activities in pancreatic ductule-derived PANC-1 and BPD-1 cells, respectively. By subsequent 5' and 3' deletion analysis, a promoter element was identified within -408 to -158, relative to the ATG codon. This promoter element was found to be cell-specific since it could drive reporter gene expression in PANC-1 and BPD-1 cells but not in Hs 262.St, Hs 746T and alphaT3-1 cells. The study of the transcriptional control of human secretin and its receptor should shed light on the pathological developments of pancreatic cancer and autism in the future.

A community strategy for Medicaid child dental services.

OBJECTIVES: The authors present second-year utilization data and first- and second-year cost data for a community-based program in Spokane County, Washington, designed to increase access to dental care for Medicaid-enrolled children from birth to 60 months of age. METHODS: The authors used Medicaid eligibility and claims data for 18,727 children 5 years of age and younger to determine utilization of dental care from January 15, 1996, through January 15, 1997. They also used accounting records from the agencies involved to calculate the first- and second-year costs of the program. RESULTS: A child in the ABCD program was 7.2 times as likely to have at least one dental visit as a Medicaid-enrolled child not in the program. Estimated costs per child with at least one dental visit (in 1995 dollars) were $54.30 for the first year and $44.38 for the second year, or $20.09 per enrolled child for the first year and $18.77 for the second year. CONCLUSION: Public-private joint efforts are effective in improving access to dental care for Medicaid-enrolled children.

Synthesis and photophysical properties of steroid-linked porphyrin-fullerene hybrids.

[structure: see text] The photophysical properties of porphyrin-linked fullerene hybrids have generated significant interest, and a number of these hybrids synthesized by this group and others have been extensively characterized with respect to energy and charge-transfer processes that take place upon photoexcitation. Present studies of steroid-linked dyads demonstrate the extent to which through-bond effects operate in these systems.

Response- and stimulus-related ERP asymmetries in a tonal oddball task: a Laplacian analysis.

Previous studies have found greater P3 amplitude over right than left hemisphere sites in a tonal oddball task with a reaction time (RT) response. This asymmetry had a central topography, and interacted with response hand. Identification of the processes underlying these asymmetries requires the use of additional methods for separating response- and stimulus-related contributions. We applied local Hjorth and spherical spline algorithms to compute surface Laplacian topographies of ERP data recorded from 30 scalp electrodes in a pooled sample of 46 right-handed healthy adults. For both methods, the current sources underlying the late positive complex were largest at medial parietal regions, but were asymmetric at central and frontocentral sites. Although a frontocentral sink contralateral to the response hand contributed to the asymmetry of the classic P3 peak, the source asymmetry was most robust after the sink had resolved. The late source was largest at electrode C4 for right hand responses, and was further enhanced in subjects showing a dichotic left ear advantage, but was unrelated to response speed. We conclude that the right hemisphere source reflects an interaction of response-related asymmetries with right hemisphere processes responsible for pitch discrimination.