Comparative analysis of the anthelmintic efficacy of European heather extracts on Teladorsagia circumcincta and Trichostrongylus colubriformis egg hatching and larval motility.

BACKGROUND: Gastrointestinal nematode (GIN) control is traditionally achieved with the use of anthelmintic drugs, however due to regulations in organic farming and the rise in anthelmintic resistance, alternatives are sought after. A promising alternative is the use of bioactive plant feeding due to the presence of plant secondary metabolites (PSMs) such as proanthocyanidins (PAs). This study focussed on the perennial shrub heather (Ericaceae family), a plant rich in PAs, highly abundant across Europe and with previously demonstrated anthelmintic potential. METHODS: In vitro assays were used to investigate heather's anthelmintic efficacy against egg hatching and larval motility. Heather samples were collected from five European countries across two seasons, and extracts were tested against two GIN species: Teladorsagia circumcincta and Trichostrongylus colubriformis. Polyphenol group-specific ultraperformance liquid chromatography-tandem mass spectrometry analysis was performed to identify relevant polyphenol subgroups present, including the PA concentration and size and ratio of the subunits. Partial least squares analysis was performed to associate efficacy with variation in PSM composition. RESULTS: Heather extracts reduced egg hatching of both GIN species in a dose-dependent manner by up to 100%, while three extracts at the highest concentration (10 mg/ml) reduced larval motility to levels that were not significantly different from dead larvae controls. PAs, particularly the procyanidin type, and flavonol derivatives were associated with anthelmintic activity, and the particular subgroup of polyphenols associated with the efficacy was dependent on the GIN species and life stage. CONCLUSIONS: Our results provide in vitro evidence that heather, a widely available plant often managed as a weed in grazing systems, has anthelmintic properties attributed to various groups of PSMs and could contribute to sustainable GIN control in ruminant production systems across Europe.

Acupuncture for Pain.

Acupuncture has been increasingly used as an integrative or complementary therapy for pain. It is well-tolerated with little risk of serious adverse effects. Traditional acupuncture and nontraditional techniques, such as electroacupuncture and dry needling, often result in reported pain improvement. Multiple factors may contribute to variability in acupuncture's therapeutic effects, including needling technique, number of needles used, duration of needle retention, acupuncture point specificity, number of treatments, and numerous subjective (psychological) factors. Controlled trials have been published on pain syndromes, such as acupuncture for acute and chronic low back pain, knee osteoarthritis, headache, myofascial pain, neck pain, and fibromyalgia. For some conditions, enough data are available for systematic evaluations or meta-analyses. Acupuncture may provide modest benefits in the treatment of chronic low back pain, tension headache and chronic headache, migraine headache prophylaxis, and myofascial pain. Although patients receiving acupuncture for acute low back pain and knee osteoarthritis report less pain, the improvement with true (verum) acupuncture over sham acupuncture is not clinically significant for these conditions. These two conditions illustrate a recurring pattern in acupuncture trials, in which the additional improvement that can be attributed to verum over sham acupuncture, even when statistically significant, is of less clinical significance. This pattern supports the notion that acupuncture treatment has a notable placebo response, or meaning response, that may be responsible for much of its demonstrated benefits. For certain patients, especially those who are unresponsive or intolerant to standard therapies, acupuncture is a reasonable treatment option.

Extremely Thermoacidophilic Metallosphaera Species Mediate Mobilization and Oxidation of Vanadium and Molybdenum Oxides.

Certain species from the extremely thermoacidophilic genus Metallosphaera directly oxidize Fe(II) to Fe(III), which in turn catalyzes abiotic solubilization of copper from chalcopyrite to facilitate recovery of this valuable metal. In this process, the redox status of copper does not change as it is mobilized. Metallosphaera species can also catalyze the release of metals from ores with a change in the metal's redox state. For example, Metallosphaera sedula catalyzes the mobilization of uranium from the solid oxide U3O8, concomitant with the generation of soluble U(VI). Here, the mobilization of metals from solid oxides (V2O3, Cu2O, FeO, MnO, CoO, SnO, MoO2, Cr2O3, Ti2O3, and Rh2O3) was examined for M. sedula and M. prunae at 70°C and pH 2.0. Of these oxides, only V and Mo were solubilized, a process accelerated in the presence of FeCl3 However, it was not clear whether the solubilization and oxidation of these metals could be attributed entirely to an Fe-mediated indirect mechanism. Transcriptomic analysis for growth on molybdenum and vanadium oxides revealed transcriptional patterns not previously observed for growth on other energetic substrates (i.e., iron, chalcopyrite, organic compounds, reduced sulfur compounds, and molecular hydrogen). Of particular interest was the upregulation of Msed_1191, which encodes a Rieske cytochrome b6 fusion protein (Rcbf, referred to here as V/MoxA) that was not transcriptomically responsive during iron biooxidation. These results suggest that direct oxidation of V and Mo occurs, in addition to Fe-mediated oxidation, such that both direct and indirect mechanisms are involved in the mobilization of redox-active metals by Metallosphaera species.IMPORTANCE In order to effectively leverage extremely thermoacidophilic archaea for the microbially based solubilization of solid-phase metal substrates (e.g., sulfides and oxides), understanding the mechanisms by which these archaea solubilize metals is important. Physiological analysis of Metallosphaera species growth in the presence of molybdenum and vanadium oxides revealed an indirect mode of metal mobilization, catalyzed by iron cycling. However, since the mobilized metals exist in more than one oxidation state, they could potentially serve directly as energetic substrates. Transcriptomic response to molybdenum and vanadium oxides provided evidence for new biomolecules participating in direct metal biooxidation. The findings expand the knowledge on the physiological versatility of these extremely thermoacidophilic archaea.

VapC toxins drive cellular dormancy under uranium stress for the extreme thermoacidophile Metallosphaera prunae.

When abruptly exposed to toxic levels of hexavalent uranium, the extremely thermoacidophilic archaeon Metallosphaera prunae, originally isolated from an abandoned uranium mine, ceased to grow, and concomitantly exhibited heightened levels of cytosolic ribonuclease activity that corresponded to substantial degradation of cellular RNA. The M. prunae transcriptome during 'uranium-shock' implicated VapC toxins as possible causative agents of the observed RNA degradation. Identifiable VapC toxins and PIN-domain proteins encoded in the M. prunae genome were produced and characterized, three of which (VapC4, VapC7, VapC8) substantially degraded M. prunae rRNA in vitro. RNA cleavage specificity for these VapCs mapped to motifs within M. prunae rRNA. Furthermore, based on frequency of cleavage sequences, putative target mRNAs for these VapCs were identified; these were closely associated with translation, transcription, and replication. It is interesting to note that Metallosphaera sedula, a member of the same genus and which has a nearly identical genome sequence but not isolated from a uranium-rich biotope, showed no evidence of dormancy when exposed to this metal. M. prunae utilizes VapC toxins for post-transcriptional regulation under uranium stress to enter a cellular dormant state, thereby providing an adaptive response to what would otherwise be a deleterious environmental perturbation.

A Pilot Study of the Efficacy of Active Leptospermum Honey for the Treatment of Partial-Thickness Facial Burns.

OBJECTIVE: Research suggests that active Leptospermum honey (ALH) improves outcomes in patients with partial-thickness burns by enhancing healing and reepithelialization rates, as well as by protecting against antibiotic-resistant microorganisms. This study assessed the effectiveness of ALH gel on healing time, bacterial growth, patient satisfaction, and cost of treatment. DESIGN: Single-arm, prospective case series. SETTING AND PATIENTS: Seven patients (aged 7-64 years) with partial-thickness facial burns were recruited from a northeastern US burn center. INTERVENTION: All patients cleansed their wounds daily with soap and water, after which they applied ALH gel. MAIN OUTCOME MEASURES: Three physicians independently rated healing using wound photography and daily tests for the presence of exudate. Wound cultures on days 1 and 7 (±2 days) assessed bacterial growth. Patients completed a satisfaction survey at the end of treatment, and cost of treatment was calculated. MAIN RESULTS: Healing time ranged from 3 to 14 days (mean, 8.1 days). Wound cultures revealed normal bacterial growth on days 1 and 7 for all patients. Patients rated ALH gel favorably, with the most common complaint of stickiness in 5 patients. One patient experienced transient burning on application that did not interrupt treatment. Average hospital-based cost of treatment was $26.15 per patient. CONCLUSIONS: Healing time was congruent with or better than what would have been expected with standard treatment. Furthermore, despite no antibiotic treatment, wound culture results yielded no abnormal bacterial growth. Finally, patients overall reported satisfaction with treatment. The findings of this study suggest that ALH is a clinically and economically valuable treatment for partial-thickness facial burns.

Uranium extremophily is an adaptive, rather than intrinsic, feature for extremely thermoacidophilic Metallosphaera species.

Thermoacidophilic archaea are found in heavy metal-rich environments, and, in some cases, these microorganisms are causative agents of metal mobilization through cellular processes related to their bioenergetics. Given the nature of their habitats, these microorganisms must deal with the potentially toxic effect of heavy metals. Here, we show that two thermoacidophilic Metallosphaera species with nearly identical (99.99%) genomes differed significantly in their sensitivity and reactivity to uranium (U). Metallosphaera prunae, isolated from a smoldering heap on a uranium mine in Thüringen, Germany, could be viewed as a "spontaneous mutant" of Metallosphaera sedula, an isolate from Pisciarelli Solfatara near Naples. Metallosphaera prunae tolerated triuranium octaoxide (U(3)O(8)) and soluble uranium [U(VI)] to a much greater extent than M. sedula. Within 15 min following exposure to "U(VI) shock," M. sedula, and not M. prunae, exhibited transcriptomic features associated with severe stress response. Furthermore, within 15 min post-U(VI) shock, M. prunae, and not M. sedula, showed evidence of substantial degradation of cellular RNA, suggesting that transcriptional and translational processes were aborted as a dynamic mechanism for resisting U toxicity; by 60 min post-U(VI) shock, RNA integrity in M. prunae recovered, and known modes for heavy metal resistance were activated. In addition, M. sedula rapidly oxidized solid U(3)O(8) to soluble U(VI) for bioenergetic purposes, a chemolithoautotrophic feature not previously reported. M. prunae, however, did not solubilize solid U(3)O(8) to any significant extent, thereby not exacerbating U(VI) toxicity. These results point to uranium extremophily as an adaptive, rather than intrinsic, feature for Metallosphaera species, driven by environmental factors.

Diet and exercise in the management of hyperlipidemia.

Dietary factors that influence lipid levels include modification of nutritional components, consumption of specific foods, use of food additives and supplements, and major dietary approaches. The most beneficial changes result from reducing intake of saturated and trans fats; increasing intake of polyunsaturated and monounsaturated fats; fortifying foods with plant stanols or sterols; isocalorically adding tree nuts to the diet; consuming one or two alcoholic drinks per day; and adopting a Portfolio, Mediterranean, low-carbohydrate, or low-fat diet. Smaller but still beneficial effects result from reducing intake of dietary cholesterol, increasing intake of soluble fiber and soy protein, and eating fatty marine fish or taking marine-derived omega-3 fatty acid supplements. Red yeast rice supplements have effects similar to those of statin medications and are better tolerated in some patients. Regular aerobic exercise has beneficial effects on lipid levels, particularly if performed for at least 120 minutes per week. Brief physician counseling will have relatively small effects on unselected patients, so efforts should be concentrated on patients who are motivated and ready to make lifestyle changes.

Outcome predictors of pediatric extracorporeal cardiopulmonary resuscitation.

Extracorporeal cardiopulmonary resuscitation (ECPR) allows clinicians to potentially rescue pediatric patients unresponsive to traditional cardiopulmonary resuscitation (CPR). Clinical and laboratory variables predictive of survival to hospital discharge are beginning to emerge. In this retrospective, historical cohort case series, clinical, and laboratory data from 31 pediatric patients (<21 years of age) receiving ECPR from March 2000 to April 2006 at our university-affiliated, tertiary-care children's hospital were statistically analyzed in an attempt to identify variables predictive of survival to hospital discharge. Seven patients survived to hospital discharge (23%), and 24 patients died. Survival was independent of gender, age, and CPR duration. ECPR survival was, however, associated with a lower pre-ECPR phosphorus concentration (P = 0.002) and a lower pre-ECPR creatinine concentration (P = 0.05). A classification tree analysis, using, in part, a pre-ECPR phosphorus concentration threshold and a CPR ABG base excess concentration threshold, yielded a 96% nominal accuracy of predicting survival to hospital discharge or death. A large, multicenter, prospective cohort study aimed at validating these predictive variables is needed to guide appropriate ECPR patient selection. This study reveals the potential survival benefit of ECPR for pediatric patients, regardless of CPR duration prior to ECPR cannulation.

Acupuncture for pain.

Acupuncture is increasingly used as an alternative or complementary therapy for the treatment of pain. It is well tolerated, with a low risk of serious adverse effects. Traditional and modern acupuncture techniques may result in reported improvement in pain patterns. Research on acupuncture has had a number of limitations, including: incomplete understanding of the physiologic effects of acupuncture; ineffective blinding of participants; unclear adequacy of acupuncture "dose;" difficulty in identification of suitable sham or placebo treatments; and the use of standardized treatment regimens rather than the individualized approach that characterizes most acupuncture practice. Controlled trials have been published regarding acupuncture for lumbar, shoulder, and neck pain; headache; arthritis; fibromyalgia; temporomandibular joint pain; and other pain syndromes. Enough data are available for some conditions to allow systematic evaluations or meta-analyses. Based on published evidence, acupuncture is most likely to benefit patients with low back pain, neck pain, chronic idiopathic or tension headache, migraine, and knee osteoarthritis. Promising but less definitive data exist for shoulder pain, fibromyalgia, temporomandibular joint pain, and postoperative pain. Acupuncture has not been proven to improve pain from rheumatoid arthritis. For other pain conditions, there is not enough evidence to draw conclusions.

HIV transmission in Bangladesh: an analysis of IDU programme coverage.

BACKGROUND: Sentinel Surveillance found HIV had increased to 7% among street-based injection drug users (IDUs) in Central Bangladesh in 2006-2007, indicating the urgent need to increase prevention. In 2004, size estimation of groups vulnerable to HIV was done by an expert committee under the National AIDS/STD Programme, making programme coverage estimates possible for the first time. METHODS: Appropriate multipliers were applied to size information to estimate a total of 20,000-40,000 IDUs throughout the country. Data from 2003 onwards from the major needle-exchange programmes (NEPs) and detoxification services were analysed to estimate programme coverage as the proportion of the total IDU population reached by interventions, and to assess the proportion of safe injections. RESULTS: An estimated 31-61% of the upper and lower national size estimates of IDUs, respectively, were in contact with any HIV prevention effort by 2006, with an increasing trend evident over the years. Of these, 24-49% were enrolled at NEPs, and 8-16% had been through detoxification. Although there was a marked improvement over the years, it appears NEPs only provided 160 days of safe injections for every IDU reached in 2006 in the North and Southeast, and 50 days in the South and Southwest, assuming IDU inject twice daily with new needles. If all IDUs reached by programmes in the North and Southeast injected every day, 44% of injections were covered by new needles, and 14% in the South and Southwest. CONCLUSION: Within the context of an HIV epidemic among some IDU, and high levels of needle-sharing and risky sexual behaviour, the implications of the low level of programme coverage are alarming, and it is clear Bangladesh needs to take action to improve it in order to control the spread of HIV.

Narrowband UVB therapy as an effective treatment for Schamberg's disease.

A 33-year-old man presented with a 3-month history of a widespread pigmented purpuric eruption over his trunk and limbs. The clinical presentation and histology were consistent with a diagnosis of Schamberg's disease. The rash initially cleared following a short course of oral prednisolone at 25 mg daily for 3 weeks, which was weaned over the subsequent 4 weeks. Topical mometasone furoate ointment 0.1% daily was also applied to active areas. The rash recurred when prednisolone was reduced to below 5 mg per day. To prevent a further recurrence with weaning prednisolone, narrowband UVB therapy was commenced three times per week. The patient was continued on UV therapy over the next 5 months. The rash would flare after 2 to 3 weeks without treatment. The frequency of UV therapy was weaned and the patient remained clear on as little as one treatment every 2 weeks. Any further reduction, however, was associated with a recurrence. Narrowband UVB therapy should be considered for difficult or persistent cases of pigmented purpuric eruption.

Impact of substrate glycoside linkage and elemental sulfur on bioenergetics of and hydrogen production by the hyperthermophilic archaeon Pyrococcus furiosus.

Glycoside linkage (cellobiose versus maltose) dramatically influenced bioenergetics to different extents and by different mechanisms in the hyperthermophilic archaeon Pyrococcus furiosus when it was grown in continuous culture at a dilution rate of 0.45 h(-1) at 90 degrees C. In the absence of S(0), cellobiose-grown cells generated twice as much protein and had 50%-higher specific H(2) generation rates than maltose-grown cultures. Addition of S(0) to maltose-grown cultures boosted cell protein production fourfold and shifted gas production completely from H(2) to H(2)S. In contrast, the presence of S(0) in cellobiose-grown cells caused only a 1.3-fold increase in protein production and an incomplete shift from H(2) to H(2)S production, with 2.5 times more H(2) than H(2)S formed. Transcriptional response analysis revealed that many genes and operons known to be involved in alpha- or beta-glucan uptake and processing were up-regulated in an S(0)-independent manner. Most differentially transcribed open reading frames (ORFs) responding to S(0) in cellobiose-grown cells also responded to S(0) in maltose-grown cells; these ORFs included ORFs encoding a membrane-bound oxidoreductase complex (MBX) and two hypothetical proteins (PF2025 and PF2026). However, additional genes (242 genes; 108 genes were up-regulated and 134 genes were down-regulated) were differentially transcribed when S(0) was present in the medium of maltose-grown cells, indicating that there were different cellular responses to the two sugars. These results indicate that carbohydrate characteristics (e.g., glycoside linkage) have a major impact on S(0) metabolism and hydrogen production in P. furiosus. Furthermore, such issues need to be considered in designing and implementing metabolic strategies for production of biofuel by fermentative anaerobes.