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Key Points Mechanical low back pain includes lumbar strain, herniated disc with radiculopathy, facet osteoarthritis and lumbar spinal stenosis, which cumulatively account for ≥95% of cases of low back pain Most episodes of low back pain resolve without the need for radiographic or laboratory evaluation Nonsurgical management is an effective initial treatment for individuals with or without sciatica Surgical intervention is reserved for patients with sciatica who have failed conservative management after ≥6 weeks with motor weakness or intractable pain Low back pain is a common health problem that is usually attributable to mechanical disorders of the spine. In this comprehensive Review, David Borenstein outlines the usual characteristics and pathology of mechanical low back pain—from a Rheumatologist's perspective—as well as describing the available diagnostic technologies and treatment options for patients. Low back pain, in its acute and chronic forms, is one of the most common health problems and is frequently evaluated by rheumatologists. The multiple possible diagnoses associated with this symptom make correctly attributing back pain to a specific disease difficult. This dilemma necessitates an organized approach to separate patients with mechanical disorders from those with rare systemic disorders. The most common forms of back pain are mechanical. Gradual modifications in the axial skeletal structures over time result in pathological disorders that generally occur later in an individual's lifespan. The diagnostic process that identifies these mechanical disorders is straightforward and does not require expensive radiological or laboratory tests in the early phases of the evaluation. Most low back pain resolves without intervention, but some reports suggest that episodes of back pain are persistent or recurring for a substantial minority of patients. Therapies for back pain can be nonpharmacological, pharmacological or surgical. All interventions have limited capacity to resolve low back pain. Nonsurgical therapies are preferred for muscle injuries and osteoarthritis of the lumbar spine. Surgical interventions can resolve the pain and dysfunction of disc herniation and spinal stenosis more rapidly than conventional therapy, but surgical benefit wanes over time.

Type VI secretion (T6S) is a cell-to-cell injection system that can be used as a microbial weapon. T6S kills vulnerable cells, and is present in close to 25% of sequenced Gram-negative bacteria. To examine the ecological role of T6S among bacteria, we competed self-immune T6S+ cells and T6S-sensitive cells in simulated range expansions. As killing takes place only at the interface between sensitive and T6S+ strains, while growth takes place everywhere, sufficiently large domains of sensitive cells can achieve net growth in the face of attack. Indeed T6S-sensitive cells can often outgrow their T6S+ competitors. We validated these findings through in vivo competition experiments between T6S+ Vibrio cholerae and T6S-sensitive Escherichia coli. We found that E. coli can survive and even dominate so long as they have an adequate opportunity to form microcolonies at the outset of the competition. Finally, in simulated competitions between two equivalent and mutually sensitive T6S+ strains, the more numerous strain has an advantage that increases with the T6S attack rate. We conclude that sufficiently large domains of T6S-sensitive individuals can survive attack and potentially outcompete self-immune T6S+ bacteria.

Many cellular populations cooperate through the secretion of diffusible extracellular resources, such as digestive enzymes or virulence factors. Diffusion of these resources leads to long-range intercellular interactions, creating the possibility of cooperation but also the risk of exploitation by non-producing neighbors. In the past, considerable attention has been given to game-theoretic lattice models of intercellular cooperation. In these models, coexistence is commonly observed between cooperators (corresponding to resource producers) and cheaters (corresponding to nonproducers). However, these models consider only interactions between direct competitors. We find that when individuals are allowed to interact non-locally through the diffusion of a shared resource coexistence between cooperators and cheaters is lost. Instead, we find population dynamics similar to simple competition, either neutral or biased, with no balancing selection that would favor coexistence. Our results highlight the importance of an accurate treatment of diffusion of shared resources and argue against the generality of the conclusions of game-theoretic lattice models.

Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients’ lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting “responder analyses” in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. Perspective A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes.

BackgroundIn 1989, a group of sixty-seven asymptomatic individuals with no history of back pain underwent magnetic resonance imaging of the lumbar spine. Twenty-one subjects (31%) had an identifiable abnormality of a disc or of the spinal canal. In the current study, we investigated whether the findings on the scans of the lumbar spine that had been made in 1989 predicted the development of low-back pain in these asymptomatic subjects.MethodsA questionnaire concerning the development and duration of low-back pain over a seven-year period was sent to the sixty-seven asymptomatic individuals from the 1989 study. A total of fifty subjects completed and returned the questionnaire. A repeat magnetic resonance scan was made for thirty-one of these subjects. Two neuroradiologists and one orthopaedic spine surgeon interpreted the original and repeat scans in a blinded fashion, independent of clinical information. At each disc level, any radiographic abnormality, including bulging or degeneration of the disc, was identified. Radiographic progression was defined as increasing severity of an abnormality at a specific disc level or the involvement of additional levels.ResultsOf the fifty subjects who returned the questionnaire, twenty-nine (58%) had no back pain. Low-back pain developed in twenty-one subjects during the seven-year study period. The 1989 scans of these subjects demonstrated normal findings in twelve, a herniated disc in five, stenosis in three, and moderate disc degeneration in one. Eight individuals had radiating leg pain; four of them had had normal findings on the original scans, two had had spinal stenosis, one had had a disc protrusion, and one had had a disc extrusion. In general, repeat magnetic resonance imaging scans revealed a greater frequency of disc herniation, bulging, degeneration, and spinal stenosis than did the original scans.ConclusionsThe findings on magnetic resonance scans were not predictive of the development or duration of low-back pain. Individuals with the longest duration of low-back pain did not have the greatest degree of anatomical abnormality on the original, 1989 scans. Clinical correlation is essential to determine the importance of abnormalities on magnetic resonance images.

In just a few decades, China has transformed into a science and technology superpower. But how did it get here and where is it headed? Go inside high-profile tech companies and labs that are driving China’s meteoric rise to the forefront of global innovation. How does China innovate? What drives its bid for technological supremacy? And what does its rise mean for the future of the global economy?

Background: Cyclobenzaprine hydrochloride is a muscle relaxant that is effective in improving muscle spasm, reducing local pain and tenderness, and increasing range of motion in acute, painful musculoskeletal conditions. Sedation is the most common adverse event associated with its use at the usual dosage of 10 mg TID. Studies in healthy adults sugges that a lower dose may produce less sedation. Because cyclobenzaprine's duration of action is 4 to 6 hours, reducing the dosing frequency to 10 mg BID would create a potentially painful untreated interval between doses. The alternative is administration of a lower dose (eg, 5 or 2.5 mg) TID. Objective: These studies were designed to assess the efficacy and tolerability of cyclobenzaprine 2.5, 5, and 10 mg TID compared with placebo in patients with acute musculoskeletal spasm. Methods: In 2 randomized, double-blind, placebo-controlled, parallel-group trials conducted at primary care centers in the United States, adult patients with acute painful muscle spasm of the lumbar or cervical region were randomly assigned to receive treatment with 2.5, 5, or 10 mg cyclobenzaprine TID or placebo for 7 days (study 1: cyclobenzaprine 5 or 10 mg TID or placebo; study 2: cyclobenzaprine 2.5 or 5 mg TID or placebo). The primary efficacy measures were patient-rated clinical global impression of change, medication helpfulness, and relief from starting backache. Neither study included a nonsteroidal anti-inflammatory drug (NSAID) as an active control. Although physicians frequently prescribe an analgesic or NSAID in addition to cyclobenzaprine, these studies were not designed to assess whether adding cyclobenzaprine provides a benefit over that of an analgesic. Results: One thousand four hundred five patients (737 study 1; 668 study 2), two thirds with low back pain and one third with neck pain, were randomized to treatment. Their mean age was 42 years, and ∼89% were white. In both studies, patients receiving cyclobenzaprine 5 or 10 mg had significantly higher mean scores on the primary efficacy measures compared with those receiving placebo (study 1—P≤0.001 cyclobenzaprine 5 and 10 mg vs placebo, all measures at visits 2 and 3; study 2—P≤0.03 cyclobenzaprine 2.5 mg vs placebo, relief from starting backache on day 3 only; cyclobenzaprine 5 mg vs placebo, patient-rated clinical global impression of change, medication helpfulness, and relief from starting backache at visit 3 or day 7 only). On day 7, significantly more patients receiving cyclobenzaprine 5 or 10 mg reported relief compared with placebo recipients (P < 0.05 all cyclobenzaprine groups vs placebo). Onset of relief was apparent within 3 or 4 doses of the 5-mg regimen. In the subanalysis of the proportion of responders in the pooled 5-mg groups who did and did not report somnolence, a meaningful treatment effect was observed on all primary efficacy variables in patients who did not report somnolence, suggesting that efficacy was indendependent of sedation. Cyclobenzaprine was well tolerated. Somnolence and dry mouth, the most common adverse effects, were mild and dose related. Overall, ≥ 1 adverse event was reported in 54.1%, 61.8%, and 35.4% of patients receiving cyclobenzaprine 5 or 10 mg or placebo, respectively, in study 1 and by 43.9%, 55.9%, and 35.4% of patients receiving cyclobenzaprine 2.5 or 5 mg or placebo, respectively, in study 2. Adverse events were the primary reason for discontinuation of treatment in the cyclobenzaprine 5- and 10-mg groups in both studies. In study 2, ineffectiveness of therapy was the main reason for discontinuation of therapy in the group receiving cyclobenzaprine 2.5 mg. Conclusions: Cyclobenzaprine 2.5 mg TID was not significantly more effective than placebo. The cyclobenzaprine 5- and 10-mg TID regimens were associated with significantly higher mean efficacy scores compared with placebo. Cyclobenzaprine 5 mg TID was as effective as 10 mg TID, and was associated with a lower incidence of sedation.

Chronic neck pain is a common patient complaint. Despite its frequency as a clinical problem, there are few evidence-based studies that document efficacy of therapies for neck pain. The treatment of this symptom is based primarily on clinical experience. Preventing the development of chronic neck pain can be achieved by modification of the work environment with chairs that encourage proper musculoskeletal movement. The use of neck supports for sleep and active neck exercises together can improve neck pain. Passive therapies, including massage, acupuncture, mechanical traction, and electrotherapy, have limited benefit when measured by clinical trial results. NSAIDs, muscle relaxants, and pure analgesics are the mainstays of therapy. Local injections of anesthetics with or without soluble corticosteroid preparations offer additional pain relief. The purpose of these agents is to diminish pain to facilitate normal neck movement. Surgical therapy with cervical spine fusion is indicated for the rare patient with intractable neck pain resistant to all nonsurgical therapies.

Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms AI production should be a protected function not directly tied to metabolism.

A new multinational guideline for treating pain in the setting of inflammatory arthritis highlights the absence of well-designed studies to answer the myriad questions faced by clinicians. To use the recommendations as a starting point for alleviating this common condition, clinicians will need to read between the lines.