Women Want Choices: Opinions from the Share.Learn.Shape Global Internet Survey About Multipurpose Prevention Technology (MPT) Products in Development.

Women need multipurpose prevention technologies (MPTs) to simultaneously prevent sexually transmitted infections (STIs), including HIV, with or without contraception. User feedback early in product development is critical for maximizing uptake and continuation. Our global online survey (April 2017-December 2018) explored women's opinions about MPT formulations in development (e.g., fast-dissolving vaginal inserts, vaginal films, intravaginal rings, injectables, implants), preferences for long-acting or "on-demand" methods, and interest in a contraceptive MPT versus products for HIV/STI prevention alone. Of the 630 women in our final analysis (mean 30 years old; range 18-49), 68% were monogamous, 79% completed secondary education, 58% had ≥ 1 child, 56% were from sub-Saharan Africa and 82% preferred a cMPT versus HIV/STI prevention alone. There were no clear preferences for any specific product or product type (long-acting, on-demand, daily). No single product will appeal everyone, however, adding contraception is likely to increase uptake of HIV/STI prevention methods for most women.

RESUMEN: Las mujeres necesitan tecnologías de prevención multipropósito (TPM) para prevenir simultáneamente las infecciones de transmisión sexual (ITS), incluido el VIH, con o sin anticoncepción. Las opiniones de los usuarios cuando un producto comienza a desarrollarse son fundamentales para maximizar la adopción y continuación de dicho producto. Nuestra encuesta global realizada en internet (abril de 2017­diciembre de 2018) exploró las opiniones de las mujeres sobre diferentes fórmulas o dispositivos de TPM que se están desarrollando (ej., insertos vaginales de disolución rápida, láminas vaginales, anillos intravaginales, inyectables, implantes). En esta encuesta se indagó acerca de las preferencias en términos de período de acción (prolongado o breve) y propósito del uso (anticonceptivo, productos para la prevención del VIH/ITS, o ambos). De las 630 mujeres (media de 30 años; rango 18­49) en el análisis final, el 68% eran monógamas, el 79% completaron la educación secundaria, el 58% tenían ≥ 1 hijo, el 56% eran del África subsahariana y el 82% preferían una TPM con componente anticonceptivo en vez de un producto para la prevención de VIH/ITS exclusivamente. No hubo preferencias claras por ningún producto o tipo de producto específico (de acción prolongada, de acción breve, de uso diario). Ningún producto por sí solo logró abarcar todas las preferencias; sin embargo, es probable que la inclusión de métodos anticonceptivos en una TPM aumente el uso de métodos de prevención del VIH/ITS en la mayoría de las mujeres.

Updating Neuroimmune Targets in Central Nervous System Dysfunction.

Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain barrier, and the irreplaceable nature of neurons. Here, we review recent advances in the field of neuroimmunology and discuss novel strategies for targeting microglia, meningeal lymphatics, and the peripheral immune system that may lead to successful treatment of a broad range of CNS disorders. In the future, it will be important to continue to explore the vast communications between the CNS and the immune system to map out dysfunctions that attribute to diseases such as chronic neuroinflammation, autoimmunity, CNS injury, and more.

Association of tracheal mucus or blood and airway neutrophilia with racing performance in Thoroughbred horses in an Australian racing yard.

OBJECTIVES: To determine the variation of tracheal mucus scores, tracheal blood scores and transendoscopic tracheal wash (TW) cytology in a population of Thoroughbred (TB) racehorses and assess their association with racing performance. METHODS: A total of 220 endoscopic examinations were performed and TWs obtained from 155 TB racehorses. Samples were collected 60-120 min following gallop work. Tracheal mucus score, tracheal blood score and TW cytology were analysed and their association with racing performance assessed. RESULTS: Of the total examinations and samples, 194 from 135 horses fitted the criteria for inclusion. The overall prevalence of visible tracheal mucus was 2.5% (5/194) and of increased tracheal mucus was 0%. The prevalence of visible tracheal blood was 8.8% (17/194) and of increased tracheal blood was 4.6% (9/194). A total of 36% (70/194) of TWs contained elevated percentages of neutrophils and of these, 96% (67/70) occurred in the absence of any visible tracheal mucus. There was no significant association between tracheal mucus score or TW cytology and subsequent racing performance. There was a statistically significant association (P = 0.004) between increased tracheal blood scores and poor racing performance. CONCLUSIONS: Visible tracheal blood seen after strenuous exercise in clinically normal TB racehorses was a risk factor for poor racing performance, but the presence of airway neutrophilia was not. No horses in this study were found to have increased tracheal mucus, so the association of increased tracheal mucus with racing performance could not be assessed.

Optimizing the offloading properties of the total contact cast for plantar foot ulceration.

AIMS: Total contact casting is the gold standard offloading treatment for plantar foot ulceration, but the optimal technique and preferred materials are poorly defined and not readily prescribed in daily practice. We investigated in-cast pressure offloading in two types of total contact casts vs. a control condition, in patients with plantar foot ulceration. METHODS: In-cast walking pressures were collected using the Novel Pedar-X system in 20 participants with a plantar foot ulcer in two types of total contact casts: a conventional total contact cast and a cushion-modified total contact cast incorporating an inlay of 6 mm slow-rebound cellular urethane and 6 mm soft cellular urethane. Casts were compared with a canvas cast shoe to establish baseline pressure values. RESULTS: Compared with the cast shoe, the conventional total contact cast significantly reduced peak pressure at the ulcer site by 44%, mean pressure by 47% and pressure-time integral by 37% (P<0.001), while the cushion-modified total contact cast significantly reduced peak pressure at the ulcer site by 70%, mean pressure by 60% and pressure-time integral by 69% (P<0.001). Plantar pressure across the entire foot and each region of the foot was also reduced with the conventional total contact cast compared with the cast shoe, and further reduced by the cushion-modified total contact cast (P<0.05). CONCLUSIONS: The offloading properties of the total contact cast can be enhanced with a 12 mm cellular urethane cushion modification. Further well-designed trials are required to understand and validate this cast technique and to demonstrate healing rates and safety in different patient populations.

Randomized trial of custom orthoses and footwear on foot pain and plantar pressure in diabetic peripheral arterial disease.

AIM: Custom-made foot orthoses reduce plantar pressure, ulceration and amputation in patients with diabetes mellitus. There is limited evidence of their effect on foot pain. In a randomized, single-blind, sham-controlled trial, the efficacy of custom orthoses on foot pain and plantar pressure in diabetic patients with peripheral arterial disease was investigated. METHODS: Sixty-one participants were randomly assigned to either custom foot orthoses (n = 30) or sham insoles (n = 31). Both groups also received standardized walking footwear. Outcomes included foot pain and function, mean pressure, toe-brachial index, average daily steps, disability, comfort, quality of life, adherence and adverse events. A multivariate predictive model was constructed to explore factors contributing to pain relief during the trial. RESULTS: At 8 weeks, 95% of participants provided follow-up data, adherence was high and there were few adverse events. Foot pain and function scores significantly improved at 8 weeks with both custom orthoses and the sham, but there was no significant difference between groups. Custom orthoses reduced pressure significantly more than the sham. There were no significant differences between groups for toe-brachial index, daily steps, disability, comfort or quality of life. Regression modelling identified inappropriate pre-trial footwear as the strongest predictor of foot pain relief during the trial. CONCLUSIONS: Custom foot orthoses significantly reduced plantar pressure compared with the sham, but there were no significant differences between groups for pain or function. The high-quality walking footwear provided to both groups may explain this finding. Footwear should have greater emphasis as the clinical intervention.

Outcomes following prolonged preterm premature rupture of the membranes.

OBJECTIVE: Rupture of the membranes in the second trimester is reported to be associated with high rates of pregnancy loss, neonatal mortality and morbidity. This article describes the outcomes of liveborn infants delivered following a prolonged period of membrane rupture occurring before 24 weeks' gestation. PATIENTS AND SETTING: Over a 5-year period, consecutive pregnancies complicated by spontaneous rupture of the membranes before 24 weeks' gestation were identified. Evaluation of short-term outcomes before discharge of liveborn infants delivered, in a tertiary referral centre, following prolonged rupture of membranes of duration greater than 2 weeks. RESULTS: Of 98 pregnancies identified with rupture of the membranes before 24 weeks' gestation, 40 (41%) women progressed to deliver a liveborn infant following a latent period of at least 14 days. Although most liveborn infants required neonatal intensive care including mechanical ventilation (n = 38; 78%), the survival rate to hospital discharge was 70% (n = 28). Airleak occurred in 7 (25%) survivors and 8 (67%) deaths. Among the survivors, 12 (43%) required supplemental oxygen at 36 weeks' postmenstrual age and no infant had grade 3 or 4 intraventricular haemorrhage. One infant had a postmortem diagnosis of pulmonary hypoplasia and nine others had clinical features consistent with this diagnosis. Low liquor volume was not uniformly associated with a poor outcome. CONCLUSION: With full contemporary neonatal intensive care, the outcome for liveborn infants in the present cohort delivered following membrane rupture occurring before 24 weeks' gestation, of at least 14 days duration, was better than previously reported.

Local cooling for relieving pain from perineal trauma sustained during childbirth.

BACKGROUND: Perineal trauma is common during childbirth and may be painful. Contemporary maternity practice includes offering women numerous forms of pain relief, including the local application of cooling treatments. OBJECTIVES: To evaluate the effectiveness and side effects of localised cooling treatments compared with no treatment, other forms of cooling treatments and non-cooling treatments. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), CINAHL (1982 to January 2007) and contacted experts in the field. SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials (RCTs) that compared localised cooling treatment applied to the perineum with no treatment or other treatments applied to relieve pain related to perineal trauma sustained during childbirth. DATA COLLECTION AND ANALYSIS: At least two independent authors performed data extraction for each study. Analyses were performed on an intention-to-treat basis where data allowed. We sought additional information from the authors of three trials. MAIN RESULTS: Seven published RCTs were included, comparing local cooling treatments (ice packs, cold gel pads or cold/iced baths) with no treatment, hamamelis water (witch hazel), pulsed electromagnetic energy (PET), hydrocortisone/pramoxine foam [Epifoam] or warm baths. The RCTs reported on a total of 859 women. Ice packs provided improved pain relief 24 to 72 hours after birth compared with no treatment (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.41 to 0.91). Women preferred the utility of the gel pads compared with ice packs or no treatment, although no differences in pain relief were detected between the treatments. None of our comparisons of treatments resulted in differences detected in perineal oedema or bruising. Women reported more pain (RR 5.60, 95% CI 2.35 to 13.33) and used more additional analgesia (RR 4.00, 95% CI 1.44 to 11.13) following the application of ice packs compared with PET. AUTHORS' CONCLUSIONS: There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain.

Enhancement of large magnetoresistances in ruthenocuprates by Ta substitution.

An unexpected enhancement of the large negative magnetoresistance (MR) observed in RuSr(2)Nd(0.95)Y(0.15)Ce(0.9)Cu(2)O(10-delta) up to -47% at 4 K and 9 T is evidenced upon dilution of the Ru magnetic order by substitution of Ta for Ru; this enhancement of -MR scales with the cell volume.

Fetal pulse oximetry for fetal assessment in labour.

BACKGROUND: Pulse oximetry could contribute to the evaluation of fetal well-being during labour. OBJECTIVES: To compare the effectiveness and safety of fetal pulse oximetry with conventional surveillance techniques. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2006), MEDLINE (1994 to November 2006), EMBASE (1994 to November 2006) and Current Contents (1994 to November 2006). SELECTION CRITERIA: All published and unpublished randomised controlled trials that compared maternal and fetal outcomes when fetal pulse oximetry was used in labour, with or without concurrent use of conventional fetal surveillance, compared with using cardiotocography (CTG) alone. DATA COLLECTION AND ANALYSIS: At least two independent authors performed data extraction. Analyses were performed on an intention-to-treat basis. We sought additional information from the investigators of three of the reported trials. MAIN RESULTS: Five published trials comparing fetal pulse oximetry and CTG with CTG alone (or when fetal pulse oximetry values were blinded) were included. The published trials, with some unpublished data, reported on a total of 7424 pregnancies. Differing entry criteria necessitated separate analyses, rather than meta-analysis of all trials. Four trials reported no significant differences in the overall caesarean section rate between those monitored with fetal oximetry and those not monitored with fetal pulse oximetry or for whom the fetal pulse oximetry results were masked. Neonatal seizures and hypoxic ischemic encephalopathy were rare. No studies reported details of assessment of long-term disability. There was a statistically significant decrease in caesarean section for nonreassuring fetal status in the fetal pulse oximetry plus CTG group compared to the CTG group in two analyses: (i) gestation from 36 weeks with fetal blood sample (fetal blood sampling) not required prior to study entry (relative risk (RR) 0.68, 95% confidence interval (CI) 0.47 to 0.99); and (ii) when fetal blood sampling was required prior to study entry (RR 0.03, 95% CI 0.00 to 0.44). There was no statistically significant difference in caesarean section for dystocia when fetal pulse oximetry (fetal pulse oximetry) was added to CTG monitoring, compared with CTG monitoring alone, although the incidence rates varied between the trials. AUTHORS' CONCLUSIONS: The data provide limited support for the use of fetal pulse oximetry when used in the presence of a nonreassuring CTG, to reduce caesarean section for nonreassuring fetal status. The addition of fetal pulse oximetry does not reduce overall caesarean section rates. A better method to evaluate fetal well-being in labour is required.

Serum and plasma cardiac troponin I concentrations in clinically normal Thoroughbreds in training in Australia.

Cardiac troponin I is a potentially useful test to identify cardiac muscle damage in the horse. Measurements of cardiac troponin I from serum or heparinised plasma samples from 23 clinically normal Thoroughbred horses in race training were analysed through a standard Australian commercial laboratory using the ADVIA Centaur Assay. The cardiac troponin I concentrations were < 0.15 microg/L from all samples. The test was then validated using macerated equine myocardium. Cardiac troponin I concentration may be useful in determining whether poor performance in Thoroughbred horses is related to active myocardial disease.

Thoracolaryngeal reflex latencies in Thoroughbred horses with recurrent laryngeal neuropathy.

Electrolaryngeography was used to study the latencies of the thoracolaryngeal adductor reflex in Thoroughbred horses with and without recurrent laryngeal neuropathy (RLN). Latencies were compared in horses with grades 1 and 2 RLN, diagnosed by endoscopy in resting horses. The reliability of the measurements, effect of sedation and correlations of latencies with age of the horse were also studied. There was no effect of sedation on reflex latency periods. The latency of the reflex period measured to a convolved peak of the electromyographic response was significantly different in horses with grades 1 and 2 disease; medians and quartile ranges were 0.067 (0.065-0.073) and 0.072 (0.068-0.074) s, respectively (P<0.05). Significant associations were found between reflex latencies and both horse age and the grade of RLN. Reflex latency measurements are reliable and sensitive, and may assist with the clinical appraisal of Thoroughbred horses with RLN.

Successful treatment of cryptococcal pneumonia in a pony mare.

A 20-year-old Welsh Mountain Pony (212 kg) mare was initially presented for a chronic cough, fever, weight loss and low grade abdominal pain. She later developed dyspnoea, tachypnoea and exercise intolerance. The presence of multiple masses (up to 17 cm diameter) in the pulmonary parenchyma was established using lateral thoracic radiography and transthoracic ultrasonography. Encapsulated, budding yeasts were observed in smears made from transtracheal washings and needle aspirates of the pulmonary lesions. Cryptococcus gattii (synonym: Cryptococcus neoformans variety gattii; Cryptococcus bacillisporus) was cultured from the transtracheal washings and aspirates of the lung masses. The pony was successfully treated using daily intravenous infusions of amphotericin B (typically 0.5 mg/kg in 1 L 5% dextrose in water over 1 h, following premedication with 50 mg flunixin intravenously) over a 1 month period, until a cumulative dose of 3 g had been administered. Treatment was considered to be successful on the basis of progressive improvement in clinical signs, reduction in the size of pulmonary cryptococcomas, 48 kg weight gain and a reduction in the cryptococcal antigen titre from 4096 to 256, 1 year after cessation of treatment.

The prevalence and distribution of gastric ulceration in 345 racehorses.

OBJECTIVE: To report the prevalence and distribution of gastric ulceration within a group of racehorses and to describe the endoscopic appearance of gastric antrum and pyloric ulceration. DESIGN: Retrospective clinical study. PROCEDURE: Medical records from gastroscopic examinations of 345 racehorses (331 Thoroughbreds and 14 Standardbreds) were reviewed. Prevalence, distribution and severity of gastric ulcers were recorded. Lesions involving the squamous mucosa and the glandular mucosa of the antrum and pylorus were graded and compared. RESULTS: Gastric ulceration was found in 86% of racehorses. The squamous mucosa around the margo plicatus was most commonly affected. The pylorus was examined in 175 horses and 47% were ulcerated. No association was found between presence of lesions of the squamous mucosa and those of the pylorus. Low correlation was found between grade and location of lesions, with the pyloric lesion score being significantly less than the squamous mucosal lesion score. CONCLUSION: Gastric ulceration was present in a large proportion of racehorses. The pylorus was also an important site of ulceration. There was no association between presence of lesion at one site and the other, although there was a low correlation between grade of lesion and location, with the pyloric ulcer grade being lower.

Randomized comparison of the quality of realtime fetal ultrasound images transmitted by ISDN and by IP videoconferencing.

We compared the quality of realtime fetal ultrasound images transmitted using ISDN and IP networks. Four experienced obstetric ultrasound specialists viewed standard recordings in a randomized trial and rated the appearance of 30 fetal anatomical landmarks, each on a seven-point scale. A total of 12 evaluations were performed for various combinations of bandwidths (128, 384 or 768 kbit/s) and networks (ISDN or IP). The intraobserver coefficient of variation was 2.9%, 5.0%, 12.7% and 14.7% for the four observers. The mean overall ratings by each of the four observers were 4.6, 4.8, 5.0 and 5.3, respectively (a rating of 4 indicated satisfactory visualization and 7 indicated as good as the original recording). Analysis of variance showed that there were no significant interobserver variations nor significant differences in the mean scores for the different types of videoconferencing machines used. The most significant variable affecting the mean score was the bandwidth used. For ISDN, the mean score was 3.7 at 128 kbit/s, which was significantly worse than the mean score of 4.9 at 384 kbit/s, which was in turn significantly worse than the mean score of 5.9 at 768 kbit/s. The mean score for transmission using IP was about 0.5 points lower than that using ISDN across all the different bandwidths, but the differences were not significant. It appears that IP transmission in a private (non-shared) network is an acceptable alternative to ISDN for fetal tele-ultrasound and one deserving further study.

Minimum acceptable standards for digital compression of a fetal ultrasound video-clip.

If the Internet could be used as a method of transmitting ultrasound images taken in the field quickly and effectively, it would bring tertiary consultation to even extremely remote centres. The aim of the study was to evaluate the maximum degree of compression of fetal ultrasound video-recordings that would not compromise signal quality. A digital fetal ultrasound videorecording of 90 s was produced, resulting in a file size of 512 MByte. The file was compressed to 2, 5 and 10 MByte. The recordings were viewed by a panel of four experienced observers who were blinded to the compression ratio used. Using a simple seven-point scoring system, the observers rated the quality of the clip on 17 items. The maximum compression ratio that was considered clinically acceptable was found to be 1:50-1:100. This produced final file sizes of 5-10 MByte, corresponding to a screen size of 320x240 pixels, running at 15 frames/s. This study expands the possibilities for providing tertiary perinatal services to the wider community.

Fetal pulse oximetry. Instrumentation and recent clinical experience.

Despite the pressing clinical need to improve fetal intrapartum surveillance, fetal oximetry has lagged well behind its application in the neonate because of the difficulty of developing a suitable method to record data from the fetus and testing its accuracy and reproducibility. Acceptable values of oxygen saturation that indicate fetal well-being are much lower than in neonates. The development of fetal pulse oximetry instrumentation is discussed. Recent clinical data acquired using the latest instrumentation are summarized and exciting new clinical applications proposed.

Intrapartum fetal oxygen saturation monitoring in congenital fetal heart block.

Conventional intrapartum electronic fetal heart rate monitoring is not informative in certain fetal conditions because the electronically-monitored fetal heart rate pattern is uninterpretable in terms of reflecting fetal normoxia. Such fetal conditions include various cardiac dysrrhythmias and some central nervous system abnormalities. Difficulties with intrapartum fetal welfare surveillance in such conditions often lead to operative delivery as a precautionary measure. We report 2 cases of intrapartum fetal oxygen saturation monitoring in the presence of congenital complete heart block (CCHB), using the Nellcor N400/FS14 oxygen saturation monitoring system. Mean intrapartum fetal oxygen saturation (FSpO2) was 32% (SEM +/- 1%) in the first case and 48% (SEM +/- 0.3%) in the second case. In both cases, vaginal delivery of otherwise healthy infants was achieved. Fetal pulse oximetry is a promising new technique which directly measures fetal oxygenation without reference to fetal heart rate patterns. It may assist in the intrapartum fetal welfare assessment in conditions such as complete heart block, thereby helping to avoid otherwise unnecessary operative delivery.