Bovine viral diarrhoea viruses from New Zealand belong predominantly to the BVDV-1a genotype.

AIM: To determine which genotypes of bovine viral diarrhoea virus (BVDV) circulate among cattle in New Zealand. METHODS: Samples comprised BVDV-1-positive sera sourced from submissions to veterinary diagnostic laboratories in 2019 (n = 25), 2020 (n = 59) and 2022 (n = 74) from both beef and dairy herds, as well as archival BVDV-1 isolates (n = 5). Fragments of the 5' untranslated region (5' UTR) and glycoprotein E2 coding sequence of the BVDV genome were amplified and sequenced. The sequences were aligned to each other and to international BVDV-1 sequences to determine their similarities and phylogenetic relationships. The 5' UTR sequences were also used to create genetic haplotype networks to determine if they were correlated with selected traits (location, type of farm, and year of collection). RESULTS: The 5' UTR sequences from New Zealand BVDV were closely related to each other, with pairwise identities between 89% and 100%. All clustered together and were designated as BVDV-1a (n = 144) or BVDV-1c (n = 5). There was no evidence of a correlation between the 5' UTR sequence and the geographical origin within the country, year of collection or the type of farm. Partial E2 sequences from New Zealand BVDV (n = 76) showed 74-100% identity to each other and clustered in two main groups. The subtype assignment based on the E2 sequence was the same as based on the 5' UTR analysis. This is the first comprehensive analysis of genomic variability of contemporary New Zealand BVDV based on the analysis of the non-coding (5' UTR) and coding (E2) sequences. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the diversity of the viruses circulating in the country is a prerequisite for the development of effective control strategies, including a selection of suitable vaccines. The data presented suggest that New Zealand BVDV are relatively homogeneous, which should facilitate eradication efforts including selection or development of the most suitable vaccines.

Assessing attention orienting in mice: a novel touchscreen adaptation of the Posner-style cueing task.

Atypical attention orienting has been found to be impaired in many neuropsychological disorders, but the underlying neural mechanism remains unclear. Attention can be oriented exogenously (i.e., driven by salient stimuli) or endogenously (i.e., driven by one's goals or intentions). Genetic mouse models are useful tools to investigate the neurobiology of cognition, but a well-established assessment of attention orienting in mice is missing. This study aimed to adapt the Posner task, a widely used attention orienting task in humans, for use in mice using touchscreen technology and to test the effects of two attention-modulating drugs, methylphenidate (MPH) and atomoxetine (ATX), on the performance of mice during this task. In accordance with human performance, mice responded more quickly and more accurately to validly cued targets compared to invalidly cued targets, thus supporting mice as a valid animal model to study the neural mechanisms of attention orienting. This is the first evidence that mice can be trained to voluntarily maintain their nose-poke on a touchscreen and to complete attention orienting tasks using exogenous peripheral cues and endogenous symbolic cues. The results also showed no significant effects of MPH and ATX on attention orienting, although MPH improved overall response times in mice during the exogenous orienting task. In summary, the current study provides a critical translational task for assessing attention orienting in mice and to investigate the effects of attention-modulating drugs on attention orienting.

Environmental enrichment modulates affiliative and aggressive social behaviour in the neuroligin-3 R451C mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impairments in social communication and the presence of restrictive and repetitive behaviours. A mouse model expressing an autism-associated R451C mutation in the gene encoding the synaptic adhesion protein neuroligin-3 (NL3) has been extensively characterised and shows altered behaviour relevant to core traits observed in ASD. Reported impairments in social behaviours in NL3R451C mice however remain controversial due to inconsistent findings in various assays across different laboratories. Such inconsistencies could plausibly be explained by an increased susceptibility of the NL3R451C mouse social phenotype to environmental modulation. To address this, NL3R451C mice were housed in standard or enriched housing from 4 weeks of age prior to behavioural testing. Enrichment rearing enhanced direct interactions with the stranger mouse in all mice in the three-chamber social interaction test however, NL3R451C mice did not show impairment in social interaction in the three-chamber test, in contrast with previous reports. Environmental enrichment enhanced aggressive behaviour in all mice, and did not specifically alter the heightened aggressive phenotype previously described in NL3R451C mice. Specific genotype effects of enrichment included reduced anxiety-like behaviour in WT mice, and lower locomotor activity levels in NL3 mice. While genotype-specific effects of enrichment were not seen on social behaviour, the general increase in affiliative social interaction and aggression seen in all mice, indicates that these behaviours, are vulnerable to change based on housing condition. Mouse models expressing ASD-associated mutations have great utility in elucidating the neurobiology underling development of core traits and it is crucial that efforts are focussed on those models exhibiting robust phenotypes. In light of the findings in the present study, we suggest approaches to improve replicability and reproducibility in mouse models of ASD.

Investigation of association between bovine viral diarrhoea virus and cervid herpesvirus type-1, and abortion in New Zealand farmed deer.

This study tested for association between bovine viral diarrhoea virus (BVDv) and cervid herpesvirus type-1 (CvHV-1) exposure and abortion in New Zealand farmed red deer. Rising two-year-old (R2, n = 22,130) and mixed-age (MA, n = 36,223) hinds from 87 and 71 herds, respectively, throughout New Zealand were pregnancy tested using ultrasound early in gestation (Scan-1) and 55-89 days later (Scan-2) to detect mid-term abortion. Sera from aborted and non-aborted hinds at Scan-2 were tested for BVDv and CvHV-1 using virus neutralisation tests. Available uteri from aborted hinds and from hinds not rearing a calf to weaning were tested by PCR for herpesvirus DNA. In herds with aborted hinds, 10.3% of 639 R2 and 17.2% of 302 MA hinds were sero-positive for BVDv and 18.6% of 613 R2 and 68.5% of 232 MA hinds were sero-positive for CvHV-1. There was no association between BVDv sero-status and abortion at animal level (R2 p = 0.36, MA p = 0.76) whereas CvHV-1 sero-positivity was negatively associated with abortion in MA hinds (p = 0.01) but not in R2 hinds (p = 0.36), MA). Eleven of 108 uteri from aborted R2 hinds but no MA hinds were positive for herpesvirus DNA. Vaginal samples from four R2 and one MA aborted hinds tested were negative for herpesvirus DNA. A Cervid Rhadinovirus type-2 (CRhV-2) was identified in seven PCR positive uteri samples. Findings suggest that BVDv and CvHV-1 may not be associated with abortion in R2 hinds, but association needs to be tested further in MA hinds. The role of CRhV-2 requires clarification.

Comparison of an alcohol-based hand sanitation product with a traditional chlorhexidine hand scrub technique for hand hygiene preparation in an equine hospital.

AIMS: To investigate the efficacy of an alcohol gel-based hand antisepsis protocol compared with a traditional chlorhexidine-based protocol under conditions of routine clinical contamination, and following heavy faecal contamination. METHODS: Twelve adult participants were recruited and on four separate days completed a hand sanitation protocol using a chlorhexidine scrub or an alcohol-based gel, with hands that were grossly clean but contaminated or with faecal contamination. Bacterial samples were obtained from participants' hands before sanitation, immediately after and then 2 hours later. All samples were cultured on blood and MacConkey agar and bacterial colonies counted after 48 hours. RESULTS: for clean contaminated hands, the percentage reduction in bacterial colonies on blood agar immediately after hand sanitation was similar for both protocols (p=0.3), but was greater for the alcohol gel than chlorhexidine after 2 hours (p=0.005). For hands with faecal contamination, the percentage reduction in bacterial colonies on blood agar was similar for both protocols immediately and 2 hours after sanitation (p>0.2), but positive cultures were obtained on blood agar from samples collected after both protocols, for almost all participants. CONCLUSIONS: The results indicate equivalent efficacy of the alcohol-based gel and the pre-surgical chlorhexidine protocol. CLINICAL RELEVANCE: The alcohol-based gel protocol is an effective hand asepsis technique for grossly clean contaminated hands and those following faecal contamination, with comparable efficacy to chlorhexidine based scrub.

A retrospective survey into the presence of Plasmodium spp. and Toxoplasma gondii in archived tissue samples from New Zealand raptors: New Zealand falcons (Falco novaeseelandiae), Australasian harriers (Circus approximans) and moreporks (Ninox novaeseelandiae).

Human colonisation of New Zealand has resulted in the introduction of emerging diseases, such as avian malaria and toxoplasmosis, which arrived with their exotic avian and mammalian hosts. Plasmodium spp. and Toxoplasma gondii have a wide host range, and several species of endemic New Zealand birds have developed a fatal disease following infection with either pathogen. However, no reports of either toxoplasmosis or avian malaria in New Zealand raptors, namely, the New Zealand falcons (Falco novaeseelandiae), Australasian harriers (Circus approximans) and moreporks (Ninox novaeseelandiae) exist in the literature. Therefore, this study was designed to determine if these two pathogens are present in these raptors through a retrospective analysis of archived tissue samples. Detection and isolate identification of these pathogens was determined using established histological and molecular techniques. All three species of New Zealand raptors tested positive for the presence of Plasmodium spp. (10/117; 8.5%) and an atypical genotype of T. gondii (9/117; 7.7%). Plasmodium lineages identified include P. elongatum GRW6, P. relictum SGS1, P. relictum PADOM02 and Plasmodium sp. LINN1. Two Australasian harriers and one morepork tested positive for the presence of both Plasmodium spp. and T. gondii. However, the pathogenicity of these organisms to the raptors is unclear as none of the tissues showed histological evidence of clinical disease associated with Plasmodium spp. and T. gondii infections. Thus, these results demonstrate for the first time that these two potential pathogens are present in New Zealand's raptors; however, further research is required to determine the prevalence and pathogenicity of these organisms among the living populations of these birds in the country.

Brucellosis in Endangered Hector's Dolphins (Cephalorhynchus hectori).

Brucella spp infections of marine mammals are often asymptomatic but have been associated with reproductive losses and deaths. Zoonotic infections originating from marine isolates have also been described. Hector's dolphins (Cephalorhynchus hectori) are an endangered species with a declining population, and the role of infectious disease in population dynamics is not fully understood. In this study, 27 Hector's dolphins found dead around the New Zealand coastline between November 2006 and October 2010 were evaluated for lesions previously associated with cetacean brucellosis. Tissues were examined using histological, immunohistochemical, and molecular (polymerase chain reaction [PCR]) techniques. Seven of 27 dolphins (26%) had at least 1 tissue that was positive on PCR for Brucella spp. Lesions consistent with brucellosis were present in 10 of 27 (37%) dolphins, but in 8 of these dolphins Brucella infection could not be demonstrated in lesional tissues. Two dolphins (7%) were diagnosed with active brucellosis: 1 female with placentitis and metritis, and 1 stillborn male fetus. Brucella identified in these 2 dolphins had genetic similarity (99%) to Brucella pinnipedialis. The omp2a gene amplicon from the uterus of the female had 100% homology with ST27 genotype isolates from a human in New Zealand and a bottlenose dolphin of Pacific origin. The remaining 5 PCR-positive dolphins were assessed as having asymptomatic or latent infection. While most Brucella infections identified in this study appeared to be subclinical, the finding of 2 dolphins with reproductive disease due to Brucella infection suggests that this disease has the potential to affect reproductive success in this species.

Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3R451C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in NL3R451C mice. NL3R451C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in NL3R451C mice. This study is the first to show altered mating behavior in the NL3R451C mouse and has provided new insights into the aggressive phenotype in this model.

First report of systemic toxoplasmosis in a New Zealand sea lion (Phocarctos hookeri).

CASE HISTORY: A 1-year-old female New Zealand sea lion (Phocarctos hookeri) was intermittently observed in the Otago region of New Zealand over an 11-month period, always dragging her hind flippers. In December 2012 the sea lion was found dead, after a period of several days being observed to be harassed by male sea lions. PATHOLOGICAL FINDINGS: At gross postmortem examination the sea lion was in moderate body condition with signs of recent bite wounds and bruising. The lungs were dark and poorly inflated. Histological findings included meningoencephalomyelitis, radiculomyelitis of the cauda equina, myocarditis and myositis. Toxoplasmosis gondii organisms were detected histologically and following immunohistochemistry in the brain, spinal cord, spinal nerves and pelvic muscles. MOLECULAR BIOLOGY: Nested PCR analysis and sequencing confirmed the presence of T. gondii DNA in uterine and lung tissue. A variant type II T. gondii genotype was identified using multilocus PCR-restriction fragment length polymorphism analysis. DIAGNOSIS: Systemic toxoplasmosis. CLINICAL RELEVANCE: Infection with T. gondii involving the spinal cord and nerves was the likely cause of the paresis observed in this sea lion before death. Ultimately, death was attributed to crushing and asphyxiation by a male sea lion, presumably predisposed by impaired mobility. Diagnosis of toxoplasmosis in a New Zealand sea lion highlights the possibility that this disease could play a role in morbidity and mortality in this endangered species, particularly in the recently established mainland populations that are close to feline sources of T. gondii oocysts.

Translational Assays for Assessment of Cognition in Rodent Models of Alzheimer's Disease and Dementia.

Cognitive dysfunction appears as a core feature of dementia, which includes its most prevalent form, Alzheimer's disease (AD), as well as vascular dementia, frontotemporal dementia, and other brain disorders. AD alone affects more than 45 million people worldwide, with growing prevalence in aging populations. There is no cure, and therapeutic options remain limited. Gene-edited and transgenic animal models, expressing disease-specific gene mutations, illuminate pathogenic mechanisms leading to cognitive decline in AD and other forms of dementia. To date, cognitive tests in AD mouse models have not been directly relevant to the clinical presentation of AD, providing challenges for translation of findings to the clinic. Touchscreen testing in mice has enabled the assessment of specific cognitive domains in mice that are directly relevant to impairments described in human AD patients. In this review, we provide context for how cognitive decline is measured in the clinic, describe traditional methods for assessing cognition in mice, and outline novel approaches, including the use of the touchscreen platform for cognitive testing. We highlight the limitations of traditional memory-testing paradigms in mice, particularly their capacity for direct translation into cognitive testing of patients. While it is not possible to expect direct translation in testing methodologies, we can aim to develop tests that engage similar neural substrates in both humans and mice. Ultimately, that would enable us to better predict efficacy across species and therefore improve the chances that a treatment that works in mice will also work in the clinic.

Contributions of After School Programs to the Development of Fundamental Movement Skills in Children.

Fundamental movement skill (FMS) proficiency or the ability to perform basic skills (e.g., throwing, catching and jumping) has been linked to participation in lifelong physical activity. FMS proficiency amongst children has declined in the previous 15 years, with more children performing FMS at a low-mastery level. These declines may help explain the insufficient levels of participation in health promoting physical activity seen in today's youth. The after school time period (e.g., 3 to 6 p.m.), is increasingly considered an opportune time for physical activity interventions. To date, little research has examined the potential for after school programming to improve FMS proficiency. Participants (n=40, 6-10 years) of two existent physical activity based after school programs, a low-organized games and a sports-based program, were pre- and post-tested for FMS proficiency using the Test of Gross Motor Development-2 (TGMD-2) over an 11-week period. The sports-based program participants showed no improvement in FMS over the 11-week study (p=0.91, eta2=0.00) and the games-based program participants significantly improved their proficiency (p=0.00, eta2=0.30). No significant (p=0.13, eta2 = 0.06), differences were found in change in FMS scores between the low-organized games program participants and the sport-based program participants. These results suggest that after school programs with a low-organized games-based focus may support a moderate improvement in FMS proficiency in young children. Better training of after school program leaders on how to teach FMS may be necessary to assist children in acquiring sufficient proficiency in FMS.

First detection of Chlamydia psittaci from a wild native passerine bird in New Zealand.

AIMS: To undertake disease surveillance for Chlamydia psittaci in native birds as part of a pilot study to examine pathogen diversity on Hauturu-o-Toi/Little Barrier Island. To retrospectively review the Massey University post-mortem database to determine previous cases of avian chlamydiosis in New Zealand. METHODS: Mistnetting of forest birds was conducted across an elevational gradient on Hauturu-o-Toi/Little Barrier Island. Minitip culture swabs were used to collect cloacal samples from native birds. These swabs were screened for Chlamydia family DNA using two PCR methods. Positive results were sequenced. A retrospective review of the Massey University post-mortem database of all avian cases from 1990 to 2011 was conducted. RESULTS: Ten native birds including four bellbirds (Anthornis melanura), three rifleman (Acanthisitta chloris), two hihi (Notiomyces cincta), and one whitehead (Mohoua albicilla) were sampled and one otherwise healthy female hihi was positive by both PCR screening methods for Chlamydophila. Sequencing confirmed 99-100% genetic similarity to C. psittaci. A retrospective review of the Massey University post-mortem database revealed no previous diagnoses of avian chlamydiosis in wild native New Zealand birds although it has been detected in captive parrots, and wild and captive exotic pigeons. CONCLUSIONS: This is the first report of the detection of C. psittaci from a wild native bird in New Zealand. The bird was a Passeriforme from an endangered species that was captured free-living on Little Barrier Island. The incidence of avian chlamydiosis in native birds in New Zealand appears to be very low, based on the retrospective review of the post-mortem database. CLINICAL RELEVANCE: It is unlikely that avian chlamydiosis is a significant problem for hihi population health. The detection of this organism has greater significance for other more susceptible species on Little Barrier Island and for human health, particularly for conservation workers involved in wildlife translocations. It further suggests that passerine birds may be a reservoir for C. psittaci in New Zealand ecosystems.

Veterinary infection control in Australia: is there control?

There is little information relating to infection control procedures in Australian veterinary practices. This review summarises the findings of international studies in the area of zoonoses and infection control, and discusses potential reasons for the apparent complacency about these issues in veterinary practice. It is the authors' opinion that legislative changes governing veterinary practice in Australia should be implemented. The curricula in veterinary schools should also emphasise infection control. These measures would significantly improve safety issues associated with the control of zoonoses in veterinary practice.

WDM/SDM transmission of 10 x 128-Gb/s PDM-QPSK over 2688-km 7-core fiber with a per-fiber net aggregate spectral-efficiency distance product of 40,320 km·b/s/Hz.

We demonstrate 2688-km multi-span transmission using wavelength-division multiplexing (WDM) of ten 50-GHz spaced 128-Gb/s PDM-QPSK signals, space-division multiplexed (SDM) in a low-crosstalk 76.8-km seven-core fiber, achieving a record net aggregate per-fiber-spectral-efficiency-distance product of 40,320 km·b/s/Hz. The demonstration was enabled by a novel core-to-core signal rotation scheme implemented in a 7-fold, synchronized recirculating loop apparatus.

Soil warming alters nitrogen cycling in a New England forest: implications for ecosystem function and structure.

Global climate change is expected to affect terrestrial ecosystems in a variety of ways. Some of the more well-studied effects include the biogeochemical feedbacks to the climate system that can either increase or decrease the atmospheric load of greenhouse gases such as carbon dioxide and nitrous oxide. Less well-studied are the effects of climate change on the linkages between soil and plant processes. Here, we report the effects of soil warming on these linkages observed in a large field manipulation of a deciduous forest in southern New England, USA, where soil was continuously warmed 5°C above ambient for 7 years. Over this period, we have observed significant changes to the nitrogen cycle that have the potential to affect tree species composition in the long term. Since the start of the experiment, we have documented a 45% average annual increase in net nitrogen mineralization and a three-fold increase in nitrification such that in years 5 through 7, 25% of the nitrogen mineralized is then nitrified. The warming-induced increase of available nitrogen resulted in increases in the foliar nitrogen content and the relative growth rate of trees in the warmed area. Acer rubrum (red maple) trees have responded the most after 7 years of warming, with the greatest increases in both foliar nitrogen content and relative growth rates. Our study suggests that considering species-specific responses to increases in nitrogen availability and changes in nitrogen form is important in predicting future forest composition and feedbacks to the climate system.

M-ary pulse-position modulation and frequency-shift keying with additional polarization/phase modulation for high-sensitivity optical transmission.

We present a new class of optical modulation formats based on the combination of m-ary pulse-position modulation (m-PPM) or m-ary frequency-shift keying (FSK) with additional polarization and/or phase modulation, which is applied on the information carrying pulses in the case of m-PPM or on the information carrying frequency carriers in the case of m-FSK. We describe the principle and implementation of this class of optical modulation formats, and formulate their theoretical receiver sensitivities in optically pre-amplified receivers. Pilot-assisted frequency-domain equalization, similar to that used in coherent optical orthogonal frequency-division multiplexing (CO-OFDM), is used for reliable channel estimation and compensation. CO-OFDM also allows m-FSK to be implemented with high spectral efficiency. As a particular format in this class, m-PPM in combination with polarization-division-multiplexed quadrature phase-shift keying (PDM-QPSK), termed as PQ-mPPM, offers superior receiver sensitivity in optically pre-amplified receivers at bit error ratios (BERs) around the thresholds of common forward-error correction codes. Record receiver sensitivities of 3.5 photons per bit (ppb) at BER = 10(-3) and 2.7 ppb at BER = 1.5 × 10(-2) are experimentally demonstrated at 2.5 Gb/s and 6.23 Gb/s using PQ-16PPM and PQ-4PPM, respectively. We further demonstrate the transmission of a 6.23-Gb/s PQ-4PPM signal over a 370-km unrepeatered ultra-large-area-fiber span with 71.7-dB total loss budget.

Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration.

Phospholipase C-beta1 (PLC-beta1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-beta1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-beta1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-beta1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

Sodium channel blockers for cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF. OBJECTIVES: To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data. Most recent search of the Group's register: March 2006 SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Meta-analysis was limited due to differing study designs. MAIN RESULTS: Four RCTs, with a total of 205 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. For three studies, interventions for six months were completed and it was possible to calculate relative change in respiratory function (FVC). There was a significant difference found in relative change in FVC in favour of placebo (GIV analysis of weighted mean difference for FVC; 1.51% (95% confidence interval -2.77 to -0.25). There were no significant differences identified in other clinically relevant outcomes. AUTHORS' CONCLUSIONS: We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

Interventions for treating cholestasis in pregnancy.

BACKGROUND: Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric. OBJECTIVES: The objective of the review is to evaluate the effectiveness and safety of therapeutic interventions in women with a clinical diagnosis of cholestasis of pregnancy (CIP) SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and PREMEDLINE, EMBASE, CINAHL and Current Contents. Date of last search: March 2001. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared an intervention to either a placebo or alternative treatment in women with a diagnosis of intrahepatic cholestasis of pregnancy. Trials published only as abstracts were excluded. DATA COLLECTION AND ANALYSIS: Reviewers assessed identified trials for 1) eligibility and 2) methodological quality. Attempts were made to contact authors for missing data. MAIN RESULTS: Nine RCTs involving 227 women were included but adequate data for appropriate comparisons in pruritus, bile acids or liver enzymes were not consistently reported. S-adenosylmethionine (SAMe) versus placebo (four trials, 82 women): only one trial showed significantly greater improvements in pruritus, bile salts and liver enzymes with SAMe. Ursodeoxycholic acid (UDCA) versus placebo (three trials, 56 women): in two trials a significant difference in pruritus relief was not detected. One trial observed greater reductions in bile salts and liver enzymes with UDCA. Preterm births were fewer with UDCA in one study while two studies reported no difference in fetal distress incidence. Guar gum versus placebo (one trial, 48 patients): no differences in pruritus, bile salts, or fetal/neonatal outcomes were observed. Activated charcoal versus no treatment (one trial, 20 patients): the reduction in bile salts was greater with charcoal, but no difference in pruritus relief: relative risk (RR) 9.0 95% confidence interval (CI) 0.6 - 148 or fetal/neonatal outcomes. UDCA versus SAMe (two trials, 36 patients): pruritus relief was better with UDCA in one study and with SAMe in the other. UDCA was better in reducing bile acids but not liver enzymes in one trial. UDCA + SAMe versus placebo, UDCA or SAMe (one study, eight patients/arm): UDCA + SAMe versus placebo or UDCA resulted in greater improvements in pruritus, bile salts and selected liver function assays; UDCA + SAMe versus SAMe resulted in greater improvements in bile salts and ALP only. No treatments were found to be unsafe. REVIEWER'S CONCLUSIONS: There is insufficient evidence to recommend guar gum, activated charcoal, SAMe and UDCA alone or in combination in treating women with CIP. Inconsistent and inadequate reporting of results precluded pooling the results of small studies.