Best Practices for Chiropractic Management of Adult Patients With Mechanical Low Back Pain: A Clinical Practice Guideline for Chiropractors in the United States.

OBJECTIVE: The purpose of this paper was to update the previously published 2016 best-practice recommendations for chiropractic management of adults with mechanical low back pain (LBP) in the United States. METHODS: Two experienced health librarians conducted the literature searches for clinical practice guidelines and other relevant literature, and the investigators performed quality assessment of included studies. PubMed was searched from March 2015 to September 2021. A steering committee of 10 experts in chiropractic research, education, and practice used the most current relevant guidelines and publications to update care recommendations. A panel of 69 experts used a modified Delphi process to rate the recommendations. RESULTS: The literature search yielded 14 clinical practice guidelines, 10 systematic reviews, and 5 randomized controlled trials (all high quality). Sixty-nine members of the panel rated 38 recommendations. All but 1 statement achieved consensus in the first round, and the final statement reached consensus in the second round. Recommendations covered the clinical encounter from history, physical examination, and diagnostic considerations through informed consent, co-management, and treatment considerations for patients with mechanical LBP. CONCLUSION: This paper updates a previously published best-practice document for chiropractic management of adults with mechanical LBP.

An exploratory study of drinkers views of health information and warning labels on alcohol containers.

INTRODUCTION AND AIMS: To identify general and specific features of health information warning labels on alcohol beverage containers that could potentially inform the development and implementation of a new labelling regime in Australia. DESIGN AND METHODS: Mixed methods, including a cross-sectional population survey and a qualitative study of knowledge, attitudes and behaviours regarding alcohol beverage labelling. The population survey used computer-assisted telephone interviews of 1500 persons in Victoria, Australia to gauge the level of support for health information and warning labels. The qualitative study used six focus groups to test the suitability of 12 prototype labels that were placed in situ on a variety of alcohol beverage containers. RESULTS: The telephone survey found 80% to 90% support for a range of information that could potentially be mandated by government authorities for inclusion on labels (nutritional information, alcohol content, health warning, images). Focus group testing of the prototype label designs found that labels should be integrated with other alcohol-related health messages, such as government social advertising campaigns, and specific labels should be matched appropriately to specific consumer groups and beverage types. DISCUSSION AND CONCLUSION: There are high levels of public support for health information and warning labels on alcohol beverages. This study contributes much needed empirical guidance for developing alcohol beverage labelling strategies in an Australian context.

Decreased substance P and NK1 receptor immunoreactivity and function in the spinal cord dorsal horn of morphine-treated neonatal rats.

UNLABELLED: Opiate analgesic tolerance is defined as a need for higher doses of opiates to maintain pain relief after prolonged opiate exposure. Though changes in the opioid receptor undoubtedly occur during conditions of opiate tolerance, there is increasing evidence that opiate analgesic tolerance is also caused by pronociceptive adaptations in the spinal cord. We have previously observed increased glutamate release in the spinal cord dorsal horn of neonatal rats made tolerant to the opiate morphine. In this study, we investigate whether spinal substance P (SP) and its receptor, the neurokinin 1 (NK1) receptor, are also modulated by prolonged morphine exposure. Immunocytochemical studies show decreased SP- and NK1-immunoreactivity in the dorsal horn of morphine-treated rats, whereas SP mRNA in the dorsal root ganglia is not changed. Electrophysiological studies show that SP fails to activate the NK1 receptor in the morphine-treated rat. Taken together, the data indicate that chronic morphine treatment in the neonatal rat is characterized by a loss of SP effects on the NK1 receptor in lamina I of the neonatal spinal cord dorsal horn. The results are discussed in terms of compensatory spinal cord processes that may contribute to opiate analgesic tolerance. PERSPECTIVE: This article describes anatomical and physiological changes that occur in the spinal cord dorsal horn of neonatal rats after chronic morphine treatment. These changes may represent an additional compensatory process of morphine tolerance and may represent an additional therapeutic target for the retention and restoration of pain relief with prolonged morphine treatment.

Primary afferent NMDA receptors increase dorsal horn excitation and mediate opiate tolerance in neonatal rats.

Repeated exposure to opiates produces analgesic tolerance, which limits their clinical usefulness. Whole-cell voltage-clamped lamina I cells in spinal slices from opiate-tolerant neonatal rats show an increase in miniature, spontaneous, and primary afferent-evoked EPSCs when compared with lamina I cells from opiate-naive rat spinal slices. This increased excitation can be blocked by the NMDA receptor (NMDAR) antagonist APV, apparently acting at NMDARs on primary afferents. Consistent with these results, electron microscopy demonstrates an increased incidence of NMDARs in substance P-containing spinal dorsal horn primary afferent terminals in opiate-tolerant rats. Moreover, superfusion of spinal slices from opiate-tolerant rats with NMDA produces a reversible increase in miniature EPSC (mEPSC) frequency in contrast to a decrease in mEPSC frequency produced by NMDA in opiate-naive slices. Finally, NMDAR antagonists inhibit the expression of opiate tolerance both in inhibiting EPSCs in spinal slices and in inhibiting behavioral nociceptive responses to heat. NMDAR antagonists have been reported in many studies to inhibit morphine analgesic tolerance. Our studies suggest that an increase in primary afferent NMDAR expression and activity mediates a hypersensitivity to noxious stimuli and causes the inhibition of opiate efficacy, which defines tolerance.

Differential effect of glutamate transporter inhibition on EPSCs in the morphine naïve and morphine tolerant neonatal spinal cord slice.

Opioid analgesic tolerance is a phenomenon defined as a need for increasingly higher doses of opiates to maintain suitable pain relief following repeated drug exposure. Research suggests that analgesic tolerance may result from heightened NMDA receptor (NMDAR) activity, but little is known regarding the mechanisms by which this elevated NMDAR activity develops. Recent evidence suggests that glutamate transporter down-regulation follows repeated opiate exposure and contributes to heightened pain sensitivity. Though glutamate transporter inhibition has been shown to increase activity of spinal cord neurons, it is unknown whether this increase contributes to the heightened NMDAR activity that underlies opiate tolerance. We directly tested this hypothesis by comparing the effects of glutamate transporter inhibition on excitatory post-synaptic currents (EPSCs) in the spinal cord dorsal horn of opiate naïve and opiate tolerant rats. We show that non-selective glutamate transporter inhibition increases the rate of spontaneous excitatory post-synaptic currents (sEPSCs) in the opiate naïve, but not opiate tolerant slice. This potentiation occurs in the presence of the sodium channel blocker tetrodotoxin (TTX) and is blocked by the NMDAR antagonist D-2-amino-5-phosphonovalerate (APV). The sEPSC rate is elevated at baseline in the opiate tolerant spinal cord slice compared to the opiate naïve slice, and glutamate transporter inhibition eliminates this difference. Taken together, we conclude that glutamate transporter inhibition directly contributes to heightened NMDAR activity. Furthermore, we propose that the increased neural activity observed in the opiate tolerant slice is due to a state of glutamate transporter down-regulation and resultant heightened NMDAR activity.

Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat.

Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1beta on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1beta on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1beta-treated rats across the different versions of the task, suggesting that peripheral IL-1beta alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).

Systemic administration of lipopolysaccharide and interleukin-1beta have different effects on memory consolidation.

Sickness behaviour is an adaptive response to infection that includes lethargy, anorexia and of direct relevance to this work, learning and memory impairments. It has been suggested that proinflammatory cytokines may disrupt learning and memory by interfering with memory consolidation [C.R. Pugh, K. Kumagawa, M. Fleshner, L.R. Watkins, S.F. Maier, J.R. Rudy, Selective effects of peripheral lipopolysaccharide administration on contextual and auditory-cue fear conditioning, Brain Behav. Immun. 12 (1998) 212-229]. We tested whether systemic interleukin-1beta is sufficient to induce impairments in memory consolidation by comparing the effects of post-learning administration of interleukin-1beta with, the potent endotoxin, lipopolysaccharide; and saline, on retention of conditioned fear of a context. We administered an acute intraperitoneal injection of lipopolysaccharide, interleukin-1beta or saline immediately following a single conditioning episode in which rats received two tone-shock pairings. Two days following the learning episode, animals were tested for strength of conditioned responding to both the context and tone. Lipopolysaccharide-injected animals, but not interleukin-1beta-injected animals, exhibited less conditioned fear of context compared to saline-treated controls. All groups showed similar conditioned fear of tone. Our results suggest that systemic interleukin-1beta is not sufficient to disrupt memory consolidation, but rather, the synergistic actions of the proinflammatory cytokines released by lipopolysaccharide are required to disrupt memory consolidation.

Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure.

Reduced frontal N-acetylaspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. The few studies of antipsychotic-nai;ve patients are inconclusive. A recent report suggests that antipsychotic drugs may increase NAA in the dorsolateral prefrontal cortex (DLPFC). We studied 10 minimally treated (less than 3 weeks lifetime exposure) schizophrenia patients and 10 normal controls with single-voxel proton magnetic resonance spectroscopy (1H-MRS) of the left frontal and occipital lobes. Concentrations of NAA, Cho, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind design with either haloperidol or quetiapine. 1H-MRS was repeated within a year. There were no differences in frontal or occipital NAA between patients and controls at baseline. However, frontal NAA was reduced in the schizophrenia group within the first year of treatment. Patients had a clear clinical response to treatment but changes in frontal NAA were not correlated with symptom improvement. The well-described reduced frontal NAA in schizophrenia may not be a trait of the illness but may represent medication effect or progression of the disease.

Observation of conserved solution-phase secondary structure in gas-phase tryptic peptides.

Results from ion mobility studies of tryptic peptides suggest that, in some cases, the gas-phase structures can be related to the solution-phase structure of the parent protein. The interpretation of ion mobility measurements is supported by results from molecular modeling and H/D exchange experiments on the same peptides. This study clearly illustrates the utility of IM-MS for screening complex mixtures for peptides having intrinsically stable secondary/tertiary structures, and/or posttranslational modification.

Unique reactivity of a tetradentate N(2)S(2) complex of nickel: intermediates in the production of sulfur oxygenates.

Complex 1 [(N,N'-dimethyl-N,N'-bis(2-sulfanylethyl)ethylenediamine)nickel(II)], previously shown to react with H(2)O(2) to produce the fully oxygenated disulfonate 5 [diaqua(N,N'-dimethyl-N,N'-bis(2-sulfonatoethyl)ethylenediamine)nickel(II)], has been explored in detail to explain the observed reactivity of this compound and to discern intermediates in the oxygenation reaction. Reaction of 1 with 1 equiv of methyl iodide results in the monomethylated square-planar nickel complex 2 [[(N,N'-dimethyl-N-(2-sulfanylethyl)-N'-(2-methylthioethyl)(ethylenediamine)nickel(II)] iodide], while a slight excess of methyl iodide results in the dimethylated complex 3 [diiodo(N,N'-dimethyl-N,N'-bis(2-methylthioethyl)ethylenediamine)nickel(II)], an X-ray structure of which has shown that the nickel ion is in an octahedral N(2)S(2)I(2) environment. Crystal data of 3: monoclinic, a = 8.865(3) A, b = 14.419(4) A, c = 14.389(6) A, beta = 100.19(3) degrees, V = 1810.2(12) A(3), space group P2(1)/n, Z = 4. The equatorial positions are occupied by the two cis-amine N-atoms and the coordinated iodides, while the axial positions are occupied by the thioether sulfur atoms. In organic solvents, the dithiolate complex 1 reacts with molecular oxygen or H(2)O(2) to produce the mixed sulfinato/thiolato complex 4 [(N,N'-dimethyl-N-(2-sulfanylethyl)-N'-(2-sulfinatoethyl)(ethylenediamine)nickel(II)], and the fully oxidized product 5. X-ray analysis of complex 4 reveals a square-planar geometry in which the nickel ion is coordinated by two cis-amine nitrogens, one thiolate sulfur donor, and one sulfinato sulfur donor. Crystal data of 4: orthorhombic, a = 11.659(2) A, b = 13.119(3) A, c = 16.869(3) A, V = 2580.2(9) A(3), space group Pbca, Z = 8. This complex is the only intermediate in the oxygenation reaction that could be isolated, and it is shown to be further reactive toward O(2) to yield the fully oxidized product 5. For a better understanding of the reactivity observed for 4, DFT calculations have been undertaken, which show a possible reaction path toward the fully oxidized product 5.

Homologous series of redox-active, dinuclear cations [M(2)(O(2)CCH(3))(2)(pynp)(2)](2+) (M = Mo, Ru, Rh) with the bridging ligand 2-(2-pyridyl)-1,8-naphthyridine (pynp).

A homologous series of dinuclear compounds with the bridging ligand 2-(2-pyridyl)-1,8-naphthyridine (pynp) has been prepared and characterized by X-ray crystallographic and spectroscopic methods. [Mo(2)(O(2)CCH(3))(2)(pynp)(2)][BF(4)](2) x 3CH(3)CN (1) crystallizes in the monoclinic space group P2(1)/c with a = 15.134(5) A, b = 14.301(6) A, c = 19.990(6) A, beta = 108.06(2) degrees, V = 4113(3) A(3), and Z = 4. [Ru(2)(O(2)CCH(3))(2)(pynp)(2)][PF(6)](2) x 2CH(3)OH (2) crystallizes in the monoclinic space group C2/c with a = 14.2228(7) A, b = 20.3204(9) A, c = 14.1022(7) A, beta = 95.144(1) degrees, V = 4059.3(3) A(3), and Z = 4. [Rh(2)(O(2)CCH(3))(2)(pynp)(2)][BF(4)](2) x C(7)H(8) (3) crystallizes in the monoclinic space group C2/c with a = 13.409(2) A, b = 21.670(3) A, c = 13.726(2) A, beta = 94.865(2) degrees, V = 3973.9(8) A(3), and Z = 4. A minor product, [Rh(2)(O(2)CCH(3))(2)(pynp)(2)(CH(3)CN)(2)][BF(4)][PF(6)] x 2CH(3)CN (4), was isolated from the mother liquor after crystals of 3 had been harvested; this compound crystallizes in the triclinic space group, P1 with a = 12.535(3) A, b = 13.116(3) A, c = 13.785(3) A, alpha = 82.52(3) degrees, beta = 77.70(3) degrees, gamma = 85.76(3) degrees, V = 2193.0(8) A(3), and Z = 2. Compounds 1-3 constitute a convenient series for probing the influence of the electronic configuration on the extent of mixing of the M-M orbitals with the pi system of the pynp ligand. Single point energy calculations performed on 1-3 at the B3LYP level of theory lend insight into the bonding in these compounds and allow for correlations to be made with electronic spectral data. Although purely qualitative in nature, the values for normalized change in orbital energies (NCOE) of the frontier orbitals before and after reduction are in agreement with the observed differences in reduction potentials as determined by cyclic voltammetry.

Distinguishing between phosphorylated and nonphosphorylated peptides with ion mobility-mass spectrometry.

Mass spectrometry has become an indispensable tool in identifying post-translationally modified proteins, but multiple peptide mass-mapping/peptide-sequencing experiments are required to answer questions involving the site and type of modification present. Here, we apply ion mobility-mass spectrometry (IM-MS), a high-throughput analysis method having high selectivity and sensitivity, to the challenge of identifying phosphorylated peptides. Ion mobility separation is based on the collision cross-section of the ion. Phosphorylation can result in a conformational change in gas-phase peptide ions, which can be detected by IM. To demonstrate this point, a peptide mixture containing a variety of peptide sequences is examined with IM-MS and molecular dynamics calculations. During the course of these studies, two classes of phosphopeptide were identified: (i) phosphorylated peptide ions that have conformers that differ from the nonphosphorylated ion and (ii) phosphorylated peptide ions that have conformations that are very similar to the nonphosphorylated peptide. The utility of IM-MS peptide mass mapping for identifying both types of phosphorylated peptides is discussed.