Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models.

New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal meningitis in order to identify treatments with the most potential to progress to clinical trials. Studies testing therapy adjunctive to antibiotics in animal models of pneumococcal meningitis were included.

Stakeholders' perceptions and preferences towards industrial water sensitive development in New Zealand.

Understanding stakeholders' perceptions and preferences is key to promoting Industrial Water Sensitive Design (IWSD). A questionnaire was distributed to stakeholders in a conventional New Zealand industrial area. The results showed that technological feasibility limitation, institutional inertia, and cognitive shortage were the main barriers to IWSD application, though stakeholders supported IWSD and preferred the vegetation-based measures.

Clinical features and prognostic factors in Covid-19: A prospective cohort study.

Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies.

Methods: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling.

Demonstrating the need to simultaneously implement all water sensitive design methods for aquatic ecosystem health.

The practices commonly known as 'Water Sensitive Design', or 'Low Impact Urban Design and Development', provide a comprehensive package of practices, (building blocks), that respect and work with the natural water cycle and enhance biodiversity. Much previous research has focussed on determining the sustainability gains achieved by the implementation of a narrow range of closely related techniques, such as the installation of at-source devices for stormwater retention and treatment. Other research has investigated the gains for the health of an ecosystem from the reduction of impervious surfaces, or from riparian revegetation, or from the clustering together of buildings.

Effect of exercise and/or reduced calorie dietary interventions on breast cancer-related endogenous sex hormones in healthy postmenopausal women.

Background: Physical inactivity and being overweight are modifiable lifestyle risk factors that consistently have been associated with a higher risk of postmenopausal breast cancer in observational studies. One biologic hypothesis underlying this relationship may be via endogenous sex hormone levels. It is unclear if changes in dietary intake, physical activity, or both, are most effective in changing these hormone levels.

Long-term effects of a weight loss intervention with or without exercise component in postmenopausal women: A randomized trial.

The aim of this study was to determine the long-term effects of a weight loss intervention with or without an exercise component on body weight and physical activity. Women were randomized to diet ( = 97) or exercise ( = 98) for 16 weeks. During the intervention, both groups had achieved the set goal of 5-6 kg weight loss.

Loss of olfactory function and nutritional status in vital older adults and geriatric patients.

The aim of this cross-sectional study was to assess the association of olfactory function and nutritional status in vital older adults and geriatric patients. Three hundred forty-five vital (mean age 67.1 years) and 138 geriatric older adults (mean age 80.

Wetlands in The Netherlands and New Zealand: optimising biodiversity and carbon sequestration during urbanisation.

The halting of biodiversity decline of wetlands necessitates ecosystem protection, restoration and re-creation of all wetland types preferably in all suitable landscapes. As peat wetlands (bogs and fens) are superior as carbon stores, and because of their rarity they have a higher biodiversity value relative to other wetland types, they need to be prioritised for protection and restoration. The hydrological, pH, and nutrient conditions essential to each type of wetland that need to be understood and provided for during development are discussed for The Netherlands' and New Zealand.

Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity.

The critical role of Langerhans cells (LC) in contact hypersensitivity (CHS) was recently questioned in studies using different LC-depletion mouse models. On one hand, inducible ablation of LC led to diminished ear swelling, suggesting functional redundancy between LC and (Langerin(+)) dermal dendritic cells (DC). On the other hand, constitutive or acute depletion of LC resulted in an enhanced reaction, supporting a regulatory role of LC in CHS.

Retrospective study on the treatment outcome of surgical closure of oroantral communications.

Purpose: A retrospective cohort study concerning the surgical closure of oroantral communications (OACs) was carried out to facilitate a comparison between treatment outcomes of conventional surgical treatment and new strategies for closure of OACs. Data were statistically analyzed to gather insight into possible predictor variables of recurrent OAC.

Patients And Methods: A cohort of patients treated for an OAC from 2004 through 2008 was reviewed.

Generation of mice with a conditional null allele for Tbx2.

The T-box transcription factor Tbx2 plays important roles in patterning and development, and has been implicated in cell-cycle regulation and cancer. Conventional disruption of Tbx2 results in abnormalities of the heart, limbs, eye and other structures, and early fetal lethality. To gain insight into the role of Tbx2 in different tissues and at different stages of development, we have generated a conditional null allele of Tbx2 by flanking Exon 2 with loxP sites (Tbx2(fl2)).

Glutamine synthetase is essential in early mouse embryogenesis.

Glutamine synthetase (GS) is expressed in a tissue-specific and developmentally controlled manner, and functions to remove ammonia or glutamate. Furthermore, it is the only enzyme that can synthesize glutamine de novo. Since congenital deficiency of GS has not been reported, we investigated its role in early development.

Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD.

Background: Patients carrying the cardiac sodium channel (SCN5A) mutation 1795insD show sudden nocturnal death and signs of multiple arrhythmia syndromes including bradycardia, conduction delay, QT prolongation, and right precordial ST-elevation. We investigated the electrophysiological characteristics of a transgenic model of the murine equivalent mutation 1798insD.

Methods And Results: On 24-hour continuous telemetry and surface ECG recordings, Scn5a(1798insD/+) heterozygous mice showed significantly lower heart rates, more bradycardic episodes (pauses > or = 500 ms), and increased PQ interval, QRS duration, and QTc interval compared with wild-type mice.

Water localisation and reclamation: steps towards low impact urban design and development.

Numerous drivers are providing stimulus for increased water cycle localisation within urban neighbourhoods. This paper uses predominantly Australasian case studies to highlight trends, successes and challenges in the transition to neighbourhood centred water-based services using 'Low Impact' and 'Water Sensitive' design and development techniques. Major steps towards urban sustainability are demonstrated, for example, up to 70% reduction in the demand for potable water (Aurora, Melbourne), removal of contaminated stormwater and sewage effluent discharge to natural waterways vulnerable to nutrient or toxin accumulation, and up to 55% of the area of the greenfield site planted in indigenous species (Regis Park, New Zealand).

Anion exchanger 2 is essential for spermiogenesis in mice.

Na+-independent anion exchangers (AE) mediate electroneutral exchange of Cl- for HCO3- ions across cell membranes, being involved in intracellular pH and cell volume regulation and in transepithelial hydroionic fluxes. Bicarbonate activation of adenylyl cyclase is known to be necessary for sperm motility and sperm capacitation, and a few studies have suggested a possible role of AE carriers in reproduction. Among the four AE genes identified in mammals thus far, only Ae2 (Slc4a2) has been determined to be expressed in the male reproductive system, especially in developing spermatozoa and in epididymal epithelium.

Cardiac expression of Gal4 causes cardiomyopathy in a dose-dependent manner.

Cardiac expression of a transgene is a common approach for determining the role of gene products in the processes underlying cardiomyopathy and heart failure (HF). We have generated transgenic mice that express the 'harmless' yeast transcription factor Gal4 in the heart under control of the alpha-myosin heavy chain promoter and found that expression of this gene causes cardiomyopathy and HF, the severity of which correlated with the number of copies of the transgene integrated into the genome and with the expression level. A line with a single copy of the transgene targeted to the hprt locus correctly expressed the transgene but did not develop cardiomyopathy.

Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.

During heart development, chamber myocardium forms locally from the embryonic myocardium of the tubular heart. The atrial natriuretic factor (ANF) gene is specifically expressed in this developing chamber myocardium and is one of the first hallmarks of chamber formation. We investigated the regulatory mechanism underlying this selective expression.

Towards integrated catchment management, Whaingaroa, New Zealand.

The paper examines progress towards integrated catchment management and sustainable agriculture at Whaingaroa (Raglan), New Zealand. Application of the Canadian "Atlantic Coastal Action Program" model (ACAP) has been only partially successful within New Zealand's bicultural setting. Even before the introduction of the ACAP process there existed strong motivation and leadership by various sectors of the community.

Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation.

Objectives: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels.

A single regulatory module of the carbamoylphosphate synthetase I gene executes its hepatic program of expression.

A 469-base pair (bp) upstream regulatory fragment (URF) and the proximal promoter of the carbamoylphosphate synthetase I (CPS) gene were analyzed for their role in the regulation of spatial, developmental, and hormone-induced expression in vivo. The URF is essential and sufficient for hepatocyte-specific expression, periportal localization, perinatal activation and induction by glucocorticoids, and cAMP in transgenic mice. Before birth, the transgene is silent but can be induced by cAMP and glucocorticoids, indicating that these compounds are responsible for the activation of expression at birth.

The upstream regulatory region of the carbamoyl-phosphate synthetase I gene controls its tissue-specific, developmental, and hormonal regulation in vivo.

The carbamoyl-phosphate synthetase I gene is expressed in the periportal region of the liver, where it is activated by glucocorticosteroids and glucagon (via cyclic AMP), and in the crypts of the intestinal mucosa. The enhancer of the gene is located 6.3 kilobase pairs upstream of the transcription start site and has been shown to direct the hormone-dependent hepatocyte-specific expression in vitro.

Biosynthesis of major histocompatibility complex molecules and generation of T cells in Ii TAP1 double-mutant mice.

Major histocompatibility complex (MHC) class I and II molecules are loaded with peptides in distinct subcellular compartments. The transporter associated with antigen processing (TAP) is responsible for delivering peptides derived from cytosolic proteins to the endoplasmic reticulum, where they bind to class I molecules, while the invariant chain (Ii) directs class II molecules to endosomal compartments, where they bind peptides originating mostly from exogenous sources. Mice carrying null mutations of the TAP1 or Ii genes (TAP10) or Ii0, respectively) have been useful tools for elucidating the two MHC/peptide loading pathways.

The spatio-temporal control of the expression of glutamine synthetase in the liver is mediated by its 5'-enhancer.

In previous studies of the glutamine synthetase gene, the promoter and two enhancer elements, one in the upstream region and one within the first intron, were identified. To analyze the role of the far-upstream enhancer element in the regulation of the expression of the glutamine synthetase gene, two classes of transgenic mice were generated. In GSK mice, the basal promoter directs the expression of the chloramphenicol acetyltransferase reporter gene.