Representation of marginalised populations in digital surveillance for notifiable conditions in Australia: a systematic review.

AIM: This study aims to establish whether digital surveillance methods for notifiable diseases in Australia collect and report data in relation to marginalised populations. METHODS: The literature was systematically reviewed to identify primary research studies published between January 2005 and July 2023. Studies were included if they described an Australian digital surveillance system for notifiable conditions. The results were synthesised with a focus on evaluating the collection and reporting of data in relation to marginalised populations. RESULTS: A total of 13 articles reporting on seven surveillance systems were identified. Influenza and adverse events following immunisation were the two most common notifiable conditions monitored. A total of six surveillance systems encompassing 16 articles reported information on sub-populations. Of these, three surveillance systems (nine articles) included data on marginalised populations. CONCLUSION: The data collected or reported in relation to sub-groups that characterise diversity in terms of health care needs, access, and marginalised populations are minimal. It is recommended that a set of equity and reporting principles is established for the future creation and use of any digital surveillance system.

Population-level impact of beliefs and attitudes on vaccine decision-making in South Africa: results from the COVID-19 Vaccine Survey (2021/2022).

OBJECTIVES: In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of COVID-19 and related comorbidities worldwide. We aimed to identify the most influential "beliefs" and "attitudes" on vaccine decision-making behavior. STUDY DESIGN: This study used panel data from cross-sectional surveys. METHODS: We used the data from Black South Africans who participated in the "COVID-19 Vaccine Surveys" (November 2021 and February/March 2022) in South Africa. Besides standard risk factor analysis, such as multivariable logistic regression models, we also used the modified version of population attributable risk percent and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behavior using the methodology in multifactorial setting. RESULTS: A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall low perceived risk, concerns around efficacy, and safety were identified as the most influential factors and associated with 52%-72% (<40 years) and 34%-55% (40+ years) of the unvaccinated individuals. CONCLUSION: Our findings highlighted the most influential beliefs and attitudes on vaccine decision-making and their population-level impacts, which are likely to have significant public health implications exclusively for this population.

Regional differences in the reduction in cerebral FDG uptake induced by the ketogenic diet.

BACKGROUND: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. METHODS: A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. RESULTS: The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. CONCLUSION: In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer.

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

The Evolutionary History of Siphonophore Tentilla: Novelties, Convergence, and Integration.

Synopsis Siphonophores are free-living predatory colonial hydrozoan cnidarians found in every region of the ocean. Siphonophore tentilla (tentacle side branches) are unique biological structures for prey capture, composed of a complex arrangement of cnidocytes (stinging cells) bearing different types of nematocysts (stinging capsules) and auxiliary structures. Tentilla present an extensive morphological and functional diversity across species. While associations between tentillum form and diet have been reported, the evolutionary history giving rise to this morphological diversity is largely unexplored. Here we examine the evolutionary gains and losses of novel tentillum substructures and nematocyst types on the most recent siphonophore phylogeny. Tentilla have a precisely coordinated high-speed strike mechanism of synchronous unwinding and nematocyst discharge. Here we characterize the kinematic diversity of this prey capture reaction using high-speed video and find relationships with morphological characters. Since tentillum discharge occurs in synchrony across a broad morphological diversity, we evaluate how phenotypic integration is maintaining character correlations across evolutionary time. We found that the tentillum morphospace has low dimensionality, identified instances of heterochrony and morphological convergence, and generated hypotheses on the diets of understudied siphonophore species. Our findings indicate that siphonophore tentilla are phenotypically integrated structures with a complex evolutionary history leading to a phylogenetically-structured diversity of forms that are predictive of kinematic performance and feeding habits.

Los sifonóforos son cnidarios hidrozoos coloniales depredadores que habitan todas las regiones pelágicas del océano. Las téntilas (ramificaciones laterales de los tentáculos) de los sifonóforos son estructuras biológicas dedicadas a la captura de presas. Las téntilas se componen de una matriz compleja de cnidocitos (células urticantes) portadores de diferentes tipos de nematocistes (cápsulas urticantes) y estructuras auxiliares. Las téntilas presenta una extensa diversidad morfológica y funcional en las diferentes especies de sifonóforo. Las relaciones entre la forma de las téntilas y las dietas de los sifonóforos has sido estudiadas previamente, sin embargo, la historia evolutiva que dio lugar a esta diversidad morfológica no ha sido explorada apenas. En este estudio examinamos las adquisiciones y pérdidas evolutivas de las subestructuras de la téntila y los tipos de nematocisto utilizando la filogenia molecular más reciente de los sifonóforos. Las téntilas presentan un mecanismo de disparo a alta velocidad, sincronizando las diferentes subestructuras con gran precisión, durante el cual se la téntila de desenrolla mientras los nematocistes se disparan sobre la presa. En este estudio caracterizamos la diversidad cinemática de estas reacciones para la captura de presas utilizando video de alta velocidad, y describimos su relación con los caracteres morfológicos. Dado que la descarga de las téntilas ocurre en sincronía en toda su diversidad morfológica, hemos evaluado cómo la evolución con integración fenotípica mantiene las correlaciones entre los caracteres morfológicos a través del tiempo. Hallamos que el morfo-espacio de las téntilas tiene baja dimensionalidad, encontramos casos de heterocronía y convergencia morfológica, y generamos hipótesis sobre las dietas de especies de sifonóforo poco estudiadas. Nuestros hallazgos indican que las téntilas de los sifonóforos son estructuras con fenotipos integrados y con una historia evolutiva compleja que ha dado lugar a una diversidad filogenéticamente estructurada de formas asociadas a diferentes rendimientos cinemáticos y hábitos alimenticios.

Multidimensional analysis of human intestinal fluid composition.

The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug's solubility in human intestinal fluid (HIF), a key factor that influences bioavailability and biopharmaceutical classification. However, HIF is difficult to obtain and is known to be variable, which has led to the development of a range of simulated intestinal fluid (SIF) systems to determine drug solubility in vitro. In this study we have applied a novel multidimensional approach to analyse and characterise HIF composition using a published data set in both fasted and fed states with a view to refining the existing SIF approaches. The data set provided 152 and 172 measurements of five variables (total bile salt, phospholipid, total free fatty acid, cholesterol and pH) in time-dependent HIF samples from 20 volunteers in the fasted and fed state, respectively. The variable data sets for both fasted state and fed state are complex, do not follow normal distributions but the amphiphilic variable concentrations are correlated. When plotted 2-dimensionally a generally ellipsoid shaped data cloud with a positive slope is revealed with boundaries that enclose published fasted or fed HIF compositions. The data cloud also encloses the majority of fasted state and fed state SIF recipes and illustrates that the structured nature of design of experiment (DoE) approaches does not optimally cover the variable space and may examine media compositions that are not biorelevant. A principal component analysis in either fasted or fed state in combination with fitting an ellipsoid shape to enclose the data results in 8 points that capture over 95% of the compositional variability of HIF. The variable's average rate of concentration change in both fasted state and fed state over a short time scale (10 min) is zero and a Euclidean analysis highlights differences between the fasted and fed states and among individual volunteers. The results indicate that a 9-point DoE (8 + 1 central point) could be applied to investigate drug solubility in vitro and provide statistical solubility limits. In addition, a single point could provide a worst-case solubility measurement to define the lowest biopharmaceutical classification boundary or for use during drug development. This study has provided a novel description of HIF composition. The approach could be expanded in multiple ways by incorporation of further data sets to improve the statistical coverage or to cover specific patient groups (e.g., paediatric). Further development might also be possible to analyse information on the time dependent behaviour of HIF and to guide HIF sampling and analysis protocols.

Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.

BACKGROUND: Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure. PATIENTS AND METHODS: We obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR). RESULTS: Pre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy. CONCLUSIONS: Genomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.

Management of lateral abdominal hernias.

PURPOSE: Lateral abdominal wall hernias are rare defects but, due to their location, repair is difficult, and recurrence is common. Few studies exist to support a standard protocol for repair of these lateral hernias. We hypothesized that anchoring our repair to fixed bony structures would reduce recurrence rates. METHODS: A retrospective review of all patients who underwent lateral hernia repair at our institution was performed. RESULTS: Eight cases (seven flank and one thoracoabdominal) were reviewed. The median defect size was 105 cm2 (range 36-625 cm2). The median operative time was 185 min (range 133-282 min). There were no major complications. One patient who was repaired without mesh attachment to bony landmarks developed a recurrence at ten months and subsequently underwent reoperation. Patients with mesh secured to bony landmarks were recurrence free at a median follow-up of 171 days. CONCLUSIONS: Lateral hernias present a greater challenge due to their anatomic location. An open technique with mesh fixation to bony structures is a promising solution to this complex problem.

Hazard Group 3 agent decontamination using hydrogen peroxide vapour in a class III microbiological safety cabinet.

AIMS: This study investigated the efficacy of hydrogen peroxide vapour (HPV) at inactivating hazard group 3 bacteria that have been presented dried from their growth medium to present a realistic challenge. METHODS AND RESULTS: Hydrogen peroxide vapour technology (Bioquell) was used to decontaminate a class III microbiological safety cabinet containing biological indicators (BIs) made by drying standard working suspensions of the following agents: Bacillus anthracis (Ames) spores, Brucella abortus (strain S99), Burkholderia pseudomallei (NCTC 12939), Escherichia coli O157 ST11 (NCTC 12079), Mycobacterium tuberculosis (strain H37Rv) and Yersinia pestis (strain CO92) on stainless steel coupons. Extended cycles were used to expose the agents for 90 min. The HPV cycle completely inactivated B. anthracis spores, B. abortus, B. pseudomallei, E. coli O157 and Y. pestis when BIs were processed using quantitative and qualitative methods. Whilst M. tuberculosis was not completely inactivated, it was reduced by 4 log10 from a starting concentration of 106 colony-forming units. CONCLUSIONS: This study demonstrates that HPV is able to inactivate a range of HG3 agents at high concentrations with associated organic matter, but M. tuberculosis showed increased resistance to the process. SIGNIFICANCE AND IMPACT OF THE STUDY: This publication demonstrates that HPV can inactivate HG3 agents that have an organic load associated with them. It also shows that M. tuberculosis has higher resistance to HPV than other agents. This shows that an appropriate BI to represent the agent of interest should be chosen to demonstrate a decontamination is successful.

Church leaders' barriers and facilitators before and after implementing a physical activity and nutrition intervention.

Faith-based health promotion programs have been effective in increasing healthy eating (HE) and physical activity (PA). Very few reports exist regarding church leaders' anticipated and experienced barriers and facilitators to program implementation. Pastors (n = 38, 70%) and program coordinators (n = 54, 100%) from churches (N = 54) who attended a program training answered open-ended questions about anticipated barriers and facilitators to implementing the HE and PA parts of the Faith, Activity, and Nutrition (FAN) program. Twelve months later, pastors (n = 49, 92%) and coordinators (n = 53, 98%) answered analogous questions about their experienced barriers and facilitators to implementing the HE and PA parts of the FAN program. Responses were coded using thematic analysis. Similar themes appeared at baseline and follow-up for anticipated and experienced barriers and facilitators. The most common barriers were no anticipated barriers, resistance to change, church characteristics, and lack of participation/motivation. The most common facilitators were internal support, leadership, and communication. Few differences were found between anticipated and experienced barriers and facilitators. Understanding these perspectives, particularly overcoming resistance to change and church characteristics through strong leadership and internal support from church leaders, will improve future program development, resources, and technical assistance in faith-based and non-faith-based communities alike.

Description of Tottonophyes enigmatica gen. nov., sp. nov. (Hydrozoa, Siphonophora, Calycophorae), with a reappraisal of the function and homology of nectophoral canals.

A new species of calycophoran siphonophore, Tottonophyes enigmatica gen. nov, sp. nov., is described. It has a unique combination of traits, some shared with prayomorphs (including two rounded nectophores) and some with clausophyid diphyomorphs (the nectophores are dissimilar, with one slightly larger and slightly to the anterior of the other, and both possess a somatocyst). Molecular phylogenetic analyses indicate that the new species is the sister group to all other diphyomorphs. A new family, Tottonophyidae, is established for it. Its phylogenetic position and distinct morphology help clarify diphyomorph evolution. The function and homology of the nectophoral canals and somatocyst is also re-examined and further clarification is given to their nomenclature.

Incidence, outcomes and outcome prediction of unplanned extubation in critically ill children: An 11year experience.

PURPOSE: Unplanned extubation represents loss of control in the ICU, is associated with harm and is used as a measure of quality of care. We evaluated the rates and consequences of unplanned extubation. MATERIALS AND METHODS: Eligible patients were intubated, <18years, and in ICU. Patient, care-related and environmental characteristics were compared in patients who did and did not receive positive pressure ventilation in the 24h after events. Rates are expressed per 100 intubation-days. RESULTS: The 11,310 eligible patient-admissions identified were intubated for 75,519days; 410 (3.39%) patients had 458 unplanned extubation events (0.61 events/100 intubation-days). Annual rates of unplanned extubation reduced from 0.98 in 2004 to 0.37 in 2014. Consequences occurred in 245 (53.5%) events and included cardiac arrest in 9 (2%), bradycardia 52 (11%), and stridor 63 (14%). Positive pressure was provided after 263 (57%) events, and was independently associated with pre-event sedative and muscle relaxant drugs, non-use of restraints, respiratory reason for intubation and recent care by more nurses. CONCLUSION: Unplanned extubation was associated with both significant and no morbidity. Modification of factors including more consistent nurse staffing, restraint use, and increased vigilance in patients with previous events may potentially reduce rates and adverse consequences of unplanned extubation.

Constructed wetlands may lower inorganic nutrient inputs but enhance DOC loadings into a drinking water reservoir in North Wales.

The objective of this study was to monitor a newly constructed wetland (CW) in north Wales, UK, to assess whether it contributes to an improvement in water quality (nutrient removal) of a nearby drinking water reservoir. Inflow and outflow of the Free Water Surface (FWS) CW were monitored on a weekly basis and over a period of 6 months. Physicochemical parameters including pH, conductivity and dissolved oxygen (DO) were measured, as well as nutrients and dissolved organic and inorganic carbon (DOC, DIC) concentration. The CW was seen to contribute to water quality improvement; results show that nutrient removal took place within weeks after construction. It was found that 72 % of initial nitrate (N03 (-)), 53 % of initial phosphate (PO4 (3-)) and 35 % of initial biological oxygen demand (BOD) were removed, calculated as a total over the whole sampling period. From our study, it can be concluded that while inorganic nutrients do decline in CWs, the DOC outputs increases. This may suggest that CWs represent a source for DOC. To assess the carbon in- and output a C budget was calculated.

Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.

PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

Expression of a mitochondrial progesterone receptor in human spermatozoa correlates with a progestin-dependent increase in mitochondrial membrane potential.

The hyperactivation of human spermatozoa necessary for fertilization requires a substantial increase in cellular energy production. The factors responsible for increasing cellular energy remain poorly defined. This article proposes a role for a novel mitochondrial progesterone receptor (PR-M) in modulation of mitochondrial activity. Basic science studies demonstrate a 38 kDa protein with western blot analysis, consistent with PR-M; whereas imaging studies with confocal and immunoelectron microscopy demonstrate a PR on the mitochondria. Treatment with a PR-specific progestin shows increased mitochondrial membrane potential, not related to induction of an acrosome reaction. The increase in mitochondrial membrane potential was inhibited by a specific PR antagonist, but not affected by an inhibitor to the progesterone-dependent Catsper voltage-activated channel. In conclusion, these studies suggest expression of a novel mitochondrial PR in human spermatozoa with a progestin-dependent increase in mitochondrial activity. This mechanism may serve to enhance cellular energy production as the spermatozoa traverse the female genital tract being exposed to increasing concentrations of progesterone.

A randomized controlled trial studying efficacy and tolerance of a knee-ankle-foot orthosis used to prevent equinus in children with spastic cerebral palsy.

OBJECTIVE: To examine whether using a knee-ankle-foot orthosis helps maintain ankle-foot dorsiflexion range of motion over time. DESIGN: A multicentre randomized controlled trial. SETTING: Two hospitals and one rehabilitation centre in the Netherlands and the USA. SUBJECTS: Children (4-16 years old) with spastic cerebral palsy who were able to walk. INTERVENTION: Use of a knee-ankle-foot orthosis, equipped with an Ultraflex ankle power unit, for at least 6 hours every other night for one year. PRIMARY OUTCOME MEASURE: ankle-foot dorsiflexion range of motion. SECONDARY OUTCOME MEASURES: ankle-foot and knee angle in gait and gross motor function. Wearing time was also measured. Measurements were taken at baseline and at 3, 6, 9 and 12 months. RESULTS: 28 children (experimental group: n=15, control group: n=13) participated in the study. 11 participants (experimental: n=4, control: n=7) did not complete all five measurements, as they needed additional treatment. No significant difference was found in the decrease of ankle-foot dorsiflexion range of motion between the experimental and control groups (difference: -1.05°, 95% confidence interval: -4.71° - 2.61°). In addition, secondary outcome measures did not show differences between groups. Despite good motivation, knee-ankle-foot orthosis wearing time was limited to a mean±SD of 3.2±1.9 hours per prescribed night due to discomfort. CONCLUSIONS: Knee-ankle-foot orthosis with dynamic ankle and fixed knee are poorly tolerated and are not beneficial in preventing a reduction in ankle-foot dorsiflexion range of motion in children with spastic cerebral palsy, at least with limited use.