D-Fructose was analysed by NMR spectroscopy and previously unidentified 1H NMR resonances were assigned to the keto and α-pyranose tautomers. The full assignment of shifts for the various fructose tautomers enabled the use of 1H NMR spectroscopy in studies of the mutarotation (5 – 25 °C) and tautomeric composition at equilibrium (5 – 50 °C). The mutarotation of β-pyranose to furanose tautomers in D2O at a concentration of 0.18 M was found to have an activation energy of 62.6 kJ.mol−1. At tautomeric equilibrium (20 °C in D2O) the distribution of the β-pyranose, β-furanose, α-furanose, α-pyranose and the keto tautomers was found to be 68.23%, 22.35%, 6.24%, 2.67% and 0.50%, respectively. This tautomeric composition was not significantly affected by varying concentration between 0.089 and 0.36 M or acidification to pH 3. Upon equilibrating at 6 temperatures between 5 and 50 °C there was a linear relationship between the change in concentration and temperature for all forms.

Background. Ongoing surveillance of antimicrobial sensitivity patterns of bacteria isolated in bloodstream infections guides empiric antibiotic therapy in neonatal sepsis. Methods. Sensitivity profiles of neonatal bacterial bloodstream infections in a tertiary hospital were reviewed between 01/06/2009 and 30/06/2010 . Results. There were 246 episodes of bloodstream infection in 181 individuals—(14.06 episodes in10.35 patients/1000 patient days or 14.4 episodes in 10.6 babies/1000 live births. The majority were (93.5%) were late onset and most (54.9%) were gram positive. There were 2.28 sepsis-related deaths /1000 patient days or 2.3/1000 live births. Death was significantly associated with gram-negative infections (P < 0.001), multiple gestation (P < 0.001), shock (P = 0.008), NEC (P = 0.002), and shorter duration of hospital stay (P < 0.001). Coagulase-negative staphylococcus was isolated in 19.1%, K. pneumoniae ESBL in 12.1%, and A. baumanni in 10.9%. S. agalactiae predominated in early onset sepsis. Methicillin resistance was present in 86% of CoNS and 69.5% of S. aureus; 46% enterococcal isolates were ampicillin resistant. The majority (65%) of K. pneumoniae isolates were ESBL producers. Ampicillin resistance was present in 96% of E. coli. Conclusions. Penicillin and an aminoglycoside would be suitable empiric therapy for early onset sepsis and meropenem with gentamycin or ceftazidime with amikacin for late onset sepsis.

We report a novel isoform of β-d-[2 → 1] poly(fructo-furanosyl) α-d-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37–48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.

The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage.

Background

Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa.

Methods

The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome.

Results

178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69 - 91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85 - 90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0 - 93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome.

Conclusion

Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age.

The National Center for Biotechnology Information (NCBI) hosts 39 literature and molecular biology databases containing almost half a billion records. As the complexity of these data and associated resources and tools continues to expand, so does the need for educational resources to help investigators, clinicians, information specialists and the general public make use of the wealth of public data available at the NCBI. This review describes the educational resources available at NCBI via the NCBI Education page (www.ncbi.nlm.nih.gov/Education/). These resources include materials designed for new users, such as About NCBI and the NCBI Guide, as well as documentation, Frequently Asked Questions (FAQs) and writings on the NCBI Bookshelf such as the NCBI Help Manual and the NCBI Handbook. NCBI also provides teaching materials such as tutorials, problem sets and educational tools such as the Amino Acid Explorer, PSSM Viewer and Ebot. NCBI also offers training programs including the Discovery Workshops, webinars and tutorials at conferences. To help users keep up-to-date, NCBI produces the online NCBI News and offers RSS feeds and mailing lists, along with a presence on Facebook, Twitter and YouTube.

Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a traditional non-adjuvanted JEV vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted vaccine (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the unadjuvanted vaccine, were protected against live JEV challenge. Equine immunizations against JEV with Advax-formulated vaccine similarly showed enhanced vaccine immunogenicity, confirming that the adjuvant effects of Advax are not restricted to rodent models. Advax-adjuvanted JEV vaccine elicited a balanced T-helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV vaccine was well tolerated with minimal reactogenicity and no systemic toxicity in immunized animals. The cessation of manufacture of traditional mouse brain-derived unadjuvanted JEV vaccine in Japan has resulted in a JEV vaccine shortage internationally. There is also an ongoing lack of human vaccines against other JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture-grown JEV vaccine a promising candidate to address both needs with one vaccine.

Background

Little is known about the growth of VLBW infants in South Africa. The aim of this study was to assess the growth of a cohort of VLBW infants in Johannesburg.

Methods

A secondary analysis of a prospective cohort was conducted on 139 VLBW infants (birth weight ≤1500 g) admitted to Charlotte Maxeke Johannesburg Academic Hospital. Growth measurements were obtained from patient files and compared with the World Health Organization Child Growth Standards (WHO-CGS) and with a previous cohort of South African VLBW infants. The sample size per analysis ranged from 11 to 81 infants.

Results

Comparison with the WHO-CGS showed initial poor growth followed by gradual catch up growth with mean Z scores of 0.0 at 20 months postmenstrual age for weight, -0.8 at 20 months postmenstrual age for length and 0.0 at 3 months postmenstrual age for head circumference. Growth was comparable with that of a previous cohort of South African VLBW infants in all parameters.

Conclusions

Initial poor growth in the study sample was followed by gradual catch up growth but with persistent deficits in length for age at 20 months postmenstrual age relative to healthy term infants.

Anxiety disorders in childhood are common, disabling and run a chronic course. Cognitive behaviour therapy (CBT) is effective but expensive and trained therapists are scarce. Guided self‐help treatments may be a means of widening access to treatment. This study aimed to examine the feasibility of guided CBT self‐help in primary care for childhood anxiety disorders, specifically in terms of therapist adherence, patient and therapist satisfaction and clinical gain.

Participants were children aged between five and 12 years referred to two primary child and adolescent mental health services (PCAMHSs) in Oxfordshire, UK, who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible children, 41 anxious children were assessed for anxiety severity and interference before and after receiving CBT self‐help delivered via a parent (total therapy time = five hours) by primary mental health workers (PMHWs). Therapy sessions were rated for treatment adherence and parents and PMHWs completed satisfaction questionnaires after treatment completion. Over 80% of therapy sessions were rated at a high level of treatment adherence. Parents and PMHWs reported high satisfaction with the treatment. Sixty‐one percent of the children assessed no longer met the criteria for their primary anxiety disorder diagnosis following treatment, and 76% were rated as ‘much’/‘very much’ improved on the Clinical Global Impression–Improvement (CGI–I) scale. There were significant reductions on parent and child report measures of anxiety symptoms, interference and depression. Preliminary exploration indicated that parental anxiety was associated with child treatment outcome. The findings suggest that guided CBT self‐help represents a promising treatment for childhood anxiety in primary care.

Background

Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting.

Methods

This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival.

Results

Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31).

Conclusions

Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.

Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances.

Design Randomised controlled trial.

Setting Khayelitsha, a peri-urban settlement in South Africa.

Participants 449 pregnant women.

Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team.

Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months.

Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=−2.04 , P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=−1.76 (0.86), t=2.28 , P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale).

Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world.

Trial registration Current Controlled Trials ISRCTN25664149.