Osteopathic manipulative treatment for nonspecific low back pain: a systematic review and meta-analysis.

BACKGROUND: Nonspecific back pain is common, disabling, and costly. Therefore, we assessed effectiveness of osteopathic manipulative treatment (OMT) in the management of nonspecific low back pain (LBP) regarding pain and functional status. METHODS: A systematic literature search unrestricted by language was performed in October 2013 in electronic and ongoing trials databases. Searches of reference lists and personal communications identified additional studies. Only randomized clinical trials were included; specific back pain or single treatment techniques studies were excluded. Outcomes were pain and functional status. Studies were independently reviewed using a standardized form. The mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) and overall effect size were calculated at 3 months posttreatment. GRADE was used to assess quality of evidence. RESULTS: We identified 307 studies. Thirty-one were evaluated and 16 excluded. Of the 15 studies reviewed, 10 investigated effectiveness of OMT for nonspecific LBP, 3 effect of OMT for LBP in pregnant women, and 2 effect of OMT for LBP in postpartum women. Twelve had a low risk of bias. Moderate-quality evidence suggested OMT had a significant effect on pain relief (MD, -12.91; 95% CI, -20.00 to -5.82) and functional status (SMD, -0.36; 95% CI, -0.58 to -0.14) in acute and chronic nonspecific LBP. In chronic nonspecific LBP, moderate-quality evidence suggested a significant difference in favour of OMT regarding pain (MD, -14.93; 95% CI, -25.18 to -4.68) and functional status (SMD, -0.32; 95% CI, -0.58 to -0.07). For nonspecific LBP in pregnancy, low-quality evidence suggested a significant difference in favour of OMT for pain (MD, -23.01; 95% CI, -44.13 to -1.88) and functional status (SMD, -0.80; 95% CI, -1.36 to -0.23), whereas moderate-quality evidence suggested a significant difference in favour of OMT for pain (MD, -41.85; 95% CI, -49.43 to -34.27) and functional status (SMD, -1.78; 95% CI, -2.21 to -1.35) in nonspecific LBP postpartum. CONCLUSION: Clinically relevant effects of OMT were found for reducing pain and improving functional status in patients with acute and chronic nonspecific LBP and for LBP in pregnant and postpartum women at 3 months posttreatment. However, larger, high-quality randomized controlled trials with robust comparison groups are recommended.

Effectiveness of osteopathic manipulative treatment for pediatric conditions: A systematic review.

BACKGROUND: Osteopathic manipulative treatment (OMT) is commonly used by osteopaths and osteopathic physicians to manage a large variety of pediatric complaints. OBJECTIVE: The current study reviewed the literature to determine the effectiveness of OMT for all pediatric complaints. METHODS: A systematic literature search for randomized controlled trials (RCTs) unrestricted by language or publication status was performed in July 2020 in electronic and ongoing trials databases. Included studies were assessed using the Cochrane Risk of Bias (RoB) instrument. Mean difference or standard mean difference and overall effect size were calculated. Data were synthesized using the GRADE approach. RESULTS: Forty-seven RCTs examining 37 pediatric conditions were reviewed. Twenty-three studies reported significant favorable outcomes for OMT relative to the control intervention, and 14 additional studies reported non-significant outcomes, which suggested potential favorable effects of OMT. Fifteen of the studies were judged to have a low RoB, 12 had high risk, and the remainder had unclear RoB. Using GRADE, there was moderate evidence for the effectiveness of OMT for 13 of the 43 comparisons, particularly for length of hospital stay for preterm infants, but no high-quality evidence for any condition. CONCLUSIONS: Although a number of studies indicated positive results with use of OMT, few pediatric conditions have been investigated in more than one study, which results in no high-quality evidence for any condition. Additional research may change estimates of effect, and larger, high-quality RCTs focusing on a smaller range of conditions are recommended. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID: CRD42020162479.

Prevalence of Lyme disease agents and several emerging pathogens in questing ticks from the German Baltic coast.

In summer 2008, a total of 512 Ixodes ricinus (Acari: Ixodidae) ticks was collected from vegetation in four areas at the Baltic coast of Germany and tested for the presence of Lyme disease spirochetes. Among them, 293 ticks from three areas were screened for Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), rickettsiae of the spotted fever group (Rickettsiales: Rickettsiaceae), and Babesia spp. (Piroplasmida: Babesiidae), respectively. Borrelia burgdorferi sensu lato genospecies (Spirochaetales: Spirochaetaceae) were detected in 3.1% of the tick samples. The prevalence ofA. phagocytophilum was 1.0%, rickettsiae were present in 8.5%, and pathogenic Babesia spp. in 8.9% of analyzed ticks. Coinfections occurred in five ticks. With this study we report first data on the coexistence of established and emerging pathogens in questing ticks from recreational areas of northeastern Germany, indicating the need of further studies for a reliable risk assessment.

Diversity and coexistence of tick-borne pathogens in central Germany.

In total, 1000 Ixodes ricinus L. ticks were collected from a small recreational forest area in central Germany (Thuringia) and investigated for the presence of Borrelia spp., Babesia spp., Anaplasma spp., Rickettsia spp., Coxiella burnetii, and Francisella tularensis. Overall, 43.6% of the ticks were infected with at least one pathogen. In 8.4% of ticks double infections were detected, and 1.6% harbored more than two pathogens. In this study, we present data on the coexistence of established and emerging pathogens in questing nymphs and adult ticks in a recreational area in central Germany, indicating the need for further studies for a reliable risk assessment.

Coexistence of pathogens in host-seeking and feeding ticks within a single natural habitat in Central Germany.

The importance of established and emerging tick-borne pathogens in Central and Northern Europe is steadily increasing. In 2007, we collected Ixodes ricinus ticks feeding on birds (n = 211) and rodents (n = 273), as well as host-seeking stages (n = 196), in a habitat in central Germany. In order to find out more about their natural transmission cycles, the ticks were tested for the presence of Lyme disease borreliae, Anaplasma phagocytophilum, spotted fever group (SFG) rickettsiae, Francisella tularensis, and babesiae. Altogether, 20.1% of the 680 ticks examined carried at least one pathogen. Bird-feeding ticks were more frequently infected with Borrelia spp. (15.2%) and A. phagocytophilum (3.2%) than rodent-feeding ticks (2.6%; 1.1%) or questing ticks (5.1%; 0%). Babesia spp. showed higher prevalence rates in ticks parasitizing birds (13.2%) and host-seeking ticks (10.7%), whereas ticks from small mammals were less frequently infected (6.6%). SFG rickettsiae and F. tularensis were also found in ticks collected off birds (2.1%; 1.2%), rodents (1.8%; 1.5%), and vegetation (4.1%; 1.6%). Various combinations of coinfections occurred in 10.9% of all positive ticks, indicating interaction of transmission cycles. Our results suggest that birds not only are important reservoirs for several pathogens but also act as vehicles for infected ticks and might therefore play a key role in the dispersal of tick-borne diseases.

Osteopathic manipulative treatment for low back and pelvic girdle pain during and after pregnancy: A systematic review and meta-analysis.

BACKGROUND: Low back pain (LBP) is a common complaint during pregnancy. This study examined the effectiveness of osteopathic manipulative treatment (OMT) for LBP in pregnant or postpartum women. METHODS: Randomized controlled trials unrestricted by language were reviewed. Outcomes were pain and functional status. Mean difference (MD) or standard mean difference (SMD) and overall effect size were calculated. RESULTS: Of 102 studies, 5 examined OMT for LBP in pregnancy and 3 for postpartum LBP. Moderate-quality evidence suggested OMT had a significant medium-sized effect on decreasing pain (MD, -16.65) and increasing functional status (SMD, -0.50) in pregnant women with LBP. Low-quality evidence suggested OMT had a significant moderate-sized effect on decreasing pain (MD, -38.00) and increasing functional status (SMD, -2.12) in postpartum women with LBP. CONCLUSIONS: This review suggests OMT produces clinically relevant benefits for pregnant or postpartum women with LBP. Further research may change estimates of effect, and larger, high-quality randomized controlled trials with robust comparison groups are recommended.

Receptor-ligand binding assays: technologies and applications.

Receptor-ligand interactions play a crucial role in biological systems and their measurement forms an important part of modern pharmaceutical development. Numerous assay formats are available that can be used to screen and quantify receptor ligands. In this review, we give an overview over both radioactive and non-radioactive assay technologies with emphasis on the latter. While radioreceptor assays are fast, easy to use and reproducible, their major disadvantage is that they are hazardous to human health, produce radioactive waste, require special laboratory conditions and are thus rather expensive on a large scale. This has led to the development of non-radioactive assays based on optical methods like fluorescence polarization, fluorescence resonance energy transfer or surface plasmon resonance. In light of their application in high-throughput screening environments, there has been an emphasis on so called "mix-and-measure" assays that do not require separation of bound from free ligand. The advent of recombinant production of receptors has contributed to the increased availability of specific assays and some aspects of the expression of recombinant receptors will be reviewed. Applications of receptor-ligand binding assays described in this review will relate to screening and the quantification of pharmaceuticals in biological matrices.

Development and validation of a radioreceptor assay for the determination of morphine and its active metabolites in serum.

This article describes the development and validation of a radioreceptor assay for the determination of morphine and morphine-6-beta-glucuronide (M6G) in serum. The assay is based on competitive inhibition of the mu-opioid-selective radiolabeled ligand [3H]-DAMGO by opioid ligands (e.g. M6G) for binding to the striatal opioid receptor. The assay has been validated according to the Washington Conference Report on Analytical Method Validation. The radioreceptor assay can be performed in serum without prior pre-treatment of the sample. Direct addition of the sample results in no significant loss in maximal binding sites, and therefore, no loss in sensitivity. The assay proves to be selective for a multitude of opioid agonists and antagonists (e.g. morphine IC50 = 4.1 nM and M6G IC50 = 12.8 nM). Moreover, morphine-3-glucuronide (M3G) displays a low affinity (IC50 = 1100 nM) for the mu-opioid receptor and according to the literature demonstrates no analgesic activity. This makes discrimination, in relation to the analgesic effect, of the two metabolites of morphine possible. The assay is fast (assay time <4h, analysis 5 min/sample), easy and the sensitivity (limit of detection (LOD) = 1.6 nM M6G-equivalents) is such that very potent agonists, like morphine and M6G, can be measured at the desired serum levels. The assay is accurate (<18%), but precision is limited if measured over several days (>35%). The assay is most accurate and precise if measured over a range from 3.5 to 40 nM M6G-equivalents. Based on the limited inter-assay precision, we propose to use this receptor assay mainly as a screening tool for neonates treated with morphine.

Exploring gaps in our knowledge on Lyme borreliosis spirochaetes--updates on complex heterogeneity, ecology, and pathogenicity.

The Lyme borreliosis complex is a heterogeneous group of tick-borne spirochaetes of the genus Borrelia (Spirochaetales: Spirochaetaceae) that are distributed all over the temperate zone of the northern hemisphere. Due to the usage of new methods for phylogenetic analysis, this group has expanded rapidly during the past 5 years. Along with this development, the number of Borrelia spp. regarded as pathogenic to humans also increased. Distribution areas as well as host and vector ranges of Lyme borreliosis agents turned out to be much wider than previously thought. Furthermore, there is evidence that ticks, reservoir hosts, and patients can be coinfected with multiple Borrelia spp. or other tick-borne pathogens, which indicates a need to establish new and well-defined diagnostic and therapeutic standards for Lyme borreliosis. This review gives a broad overview on the occurrence of Lyme borreliosis spirochaetes worldwide with particular emphasis on their vectors and vertebrate hosts as well as their pathogenic potential and resultant problems in diagnosis and treatment. Against the background that many issues regarding distribution, species identity, ecology, pathogenicity, and coinfections are still unsolved, the purpose of this article is to reveal directions for future research on the Lyme borreliosis complex.

Co-circulation of emerging tick-borne pathogens in Middle Germany.

From May until October 2007, a total of 658 Ixodes ricinus ticks were collected off birds (189), rodents (273), and vegetation (196) in a certain area of Middle Germany and investigated for infection with Babesia spp., Anaplasma phagocytophilum, and Rickettsia spp. Overall, 13.1% (86/658) of the ticks were infected with at least one pathogen; co-infections occurred in 0.6% (4/658). Babesia spp. specific DNA was detected in 9.7% (64/658) of the ticks, 1.4% (9/658) were infected with A. phagocytophilum, and 2.6% (17/658) harbored rickettsiae. At least two different Rickettsia species were identified: Rickettsia monacensis and Rickettsia helvetica. Our study provides first interesting insights into the circulation and co-circulation of several emerging pathogens not only in ticks parasitizing birds and small mammals as potential reservoirs but also in questing ticks in a single natural habitat.

Are birds reservoir hosts for Borrelia afzelii?

It is known that birds are competent reservoir hosts of particular Borrelia species like B. garinii and B. valaisiana but not for B. afzelii, a rodent-associated genospecies. Since they can carry infected ticks over long distances, they are also important covectors for Lyme borreliosis spirochaetes. To assess the role of different bird species in transmission and dispersal of Borrelia OspA types, we examined 191 Ixodes ricinus ticks from 99 birds, captured on a German conservation island in the Baltic Sea in spring 2007. Surprisingly, more than one third of the 27 positive samples were identified as B. afzelii. The cause for this unusually high prevalence remains unknown, indicating the need of further studies on bird-feeding ticks that should include a higher sample size.

The potential role of migratory birds in transmission cycles of Babesia spp., Anaplasma phagocytophilum, and Rickettsia spp.

Babesia spp., Anaplasma phagocytophilum, and Rickettsia spp. are potentially emerging tick-borne pathogens, whereas many issues about their ecology, e.g. reservoir host specificity, are still unclear. In spring 2007, we collected 191 feeding Ixodes ricinus ticks from 99 birds of 11 different species on a German bird conservation island in the Baltic Sea. Babesia spp. were detected in 4.7% (9/191), A. phagocytophilum was present in 2.6% (5/191), and Rickettsia spp. were identified in 7.3% (14/191) of the investigated ticks. Further characterization of Babesia spp. infections resulted in B. divergens and B. microti. Among the Rickettsia spp. infections, we identified at least 2 different species: R. monacensis and R. helvetica. Furthermore, 2 ticks harboured mixed infections. Our study provides first interesting insights into the role of migratory birds in the distribution of several emerging tick-borne pathogens.

Activity-based matrix metallo-protease enrichment using automated, inhibitor affinity extractions.

An automated inhibitor affinity extraction method for the activity-based enrichment of matrix metallo-proteases (MMPs) is presented. Samples containing purified MMP-12 were first extracted at different flow rates in a syringe pump setup, using cartridges packed with an MMP inhibitor affinity sorbent based on an immobilized hydroxamic acid containing peptide (PLG-NHOH) with mumol/L MMP affinity. Faster extractions, a reduced number of manual manipulations, and higher extraction yields (98.9%-99.3%) were obtained over the whole flow rate range compared to batch extractions. Application of the method to synovial fluid from a rheumatoid arthritis patient followed by gelatin-zymography revealed a strong enrichment of distinct MMPs from this biological sample that were not clearly visible in the original sample. The use of an auto-sampler and a solid-phase extraction (SPE) workstation allowed full automation of the extraction procedure with the potential for on-line coupling to further sample preparation and analytical steps. MMP-12 extractions were optimized showing that ligand density is an important factor with a clear extraction yield optimum around 5 to 7.5 mmol/L. Conditioning of the stationary phase for 1 week prior to use resulted in a further slight increase in extraction yield. Under optimal conditions, an extraction yield of 99.5% was reached with a cartridge contact time of only 13 s for MMP-12. The efficacy of the extraction method for activity-based MMP profiling was further improved by the use of a broad-spectrum MMP inhibitor with nmol/L affinity (TAPI-2). This resulted in an increased extraction yield for all tested MMPs. For MMP-1, -7, -8, -10, -12, and -13 extraction yields of at least 98.8% were obtained, while for MMP-9 (full length and catalytic domain) an extraction yield of at least 96.1% was reached.

Purification and characterization of the recombinant human dopamine D2S receptor from Pichia pastoris.

The human dopamine D2S receptor was expressed in the methylotrophic yeast Pichia pastoris, where the receptor with a molecular mass of approximately 40kDa exhibited specific and saturable binding properties. The dopamine antagonist [3H]spiperone showed an average dissociation constant K(d) of 0.6+/-0.17 nM for the dopamine D2S receptor. The receptor was solubilized using the non-ionic detergent dodecylmaltoside and purified by affinity chromatography using a Ni(2+) chelate (His-Trap) column or by batch extraction with an anti-FLAG M1 affinity resin. The receptor maintained its biological activity after solubilization and purification from the membrane protein fraction. A 244- or 185-fold enrichment, as judged by an increase in specific binding, was obtained after adsorption to the His-Trap or anti-FLAG materials, respectively.

Interlaboratory reproducibility of mobility parameters in capillary electrophoresis for substance identification in systematic toxicological analysis.

An interlaboratory pilot study was performed to determine the reproducibility of mobility parameters in capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). The study was performed by an intended small number of laboratories (three) that used different brands of instruments (two). The effective mobility was corrected using standards by a method that was recently introduced to obtain a more reproducible migration parameter. A test set of 20 acidic test compounds and 5 reference compounds were analyzed during five days in each laboratory using CZE and MEKC. Buffers used consisted of 90 mM borate set at pH 8.4 (CZE) and 20 mM phosphate, 50 mM sodium dodecyl sulfate set at pH 7.5 (MEKC). Analyses were carried out using fused-silica capillaries at an electric field strength of either 52.6 kV/m or 37.5 kV/m. The interlaboratory reproducibility (mean RSD) of the effective mobility was 3.0% for CZE and 6.7% for MEKC. After applying the correction method, these values became 3.0% for CZE and 3.3% for MEKC, which is adequate for systematic toxicological analysis (STA) applications. A significant improvement of reproducibility for the calculated corrected effective mobility mu(eff)c was observed when variations are high. Therefore, it is recommended to use the correction method in interlaboratory situations, especially when instruments and capillaries from different manufacturers are used.