Junta de Andalucía

When expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. Among various strategies employed to construct bicistronic or multicistronic vectors, an internal ribosomal entry site (IRES) has been widely used. Due to the large size and difference in expression levels between genes before and after IRES, however, a new strategy was required to replace IRES. A self-cleaving 2A peptide could be a good candidate to replace IRES because of its small size and high cleavage efficiency between genes upstream and downstream of the 2A peptide. Despite the advantages of the 2A peptides, its use is not widespread because (i) there are no publicly available cloning vectors harboring a 2A peptide gene and (ii) comprehensive comparison of cleavage efficiency among various 2A peptides reported to date has not been performed in different contexts. Here, we generated four expression plasmids each harboring different 2A peptides derived from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea asigna virus and porcine teschovirus-1, respectively, and evaluated their cleavage efficiency in three commonly used human cell lines, zebrafish embryos and adult mice. Western blotting and confocal microscopic analyses revealed that among the four 2As, the one derived from porcine teschovirus-1 (P2A) has the highest cleavage efficiency in all the contexts examined. We anticipate that the 2A-harboring cloning vectors we generated and the highest efficiency of the P2A peptide we demonstrated would help biomedical researchers easily adopt the 2A technology when bicistronic or multicistronic expression is required.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.

BACKGROUND AND PURPOSE: We aimed to establish the prevalence, characteristics, and outcomes of intracranial atherosclerosis (ICAS) in China by a large, prospective, multicenter study. METHODS: We evaluated 2864 consecutive patients who experienced an acute cerebral ischemia<7 days after symptom onset in 22 Chinese hospitals. All patients underwent magnetic resonance angiography, with measurement of diameter of the main intracranial arteries. ICAS was defined as ≥50% diameter reduction on magnetic resonance angiography. RESULTS: The prevalence of ICAS was 46.6% (1335 patients, including 261 patients with coexisting extracranial carotid stenosis). Patients with ICAS had more severe stroke at admission and stayed longer in hospitals compared with those without intracranial stenosis (median National Institutes of Health Stroke Scale score, 3 versus 5; median length of stay, 14 versus 16 days; both P<0.0001). After 12 months, recurrent stroke occurred in 3.27% of patients with no stenosis, in 3.82% for those with 50% to 69% stenosis, in 5.16% for those with 70% to 99% stenosis, and in 7.27% for those with total occlusion. Cox proportional hazards regression analyses showed that the degree of arterial stenosis, age, family history of stroke, history of cerebral ischemia or heart disease, complete circle of Willis, and National Institutes of Health Stroke Scale score at admission were independent predictors for recurrent stroke at 1 year. The highest rate of recurrence was observed in patients with occlusion with the presence of ≥3 additional risk factors. CONCLUSIONS: ICAS is the most common vascular lesion in patients with cerebrovascular disease in China. Recurrent stroke rate in our study was lower compared with those of previous clinical trials but remains unacceptably high in a subgroup of patients with severe stenosis.

STUDY DESIGN: Retrospective study. OBJECTIVES: To report a technique of vertebral column resection through a single posterior approach and its preliminary results in the treatment of moderate to severe spinal deformities with limited flexibility. SUMMARY OF BACKGROUND DATA: Vertebral column resection is a formidable operation reserved for moderate to severe deformities with limited flexibility. The authors devised a technique of vertebral column resection through a single posterior approach that offers significant advantages over the anterior-posterior vertebral column resection. METHODS: Seventy spinal deformity patients treated by posterior vertebral column resection were reviewed. Minimum follow-up was 2 years (range 2-3.3 years). There were 34 males and 36 females with a mean age of 27.4 years at the time of the operation. Etiologic diagnoses were adult scoliosis in 7, congenital kyphoscoliosis in 38, and postinfectious kyphosis in 25. The surgery consisted of temporary stabilization of the vertebral column with segmental pedicle screw fixation, resection of the vertebral column at the apex of the deformity via the posterior route, followed by gradual deformity correction and global fusion. RESULTS: The total number of resected vertebrae was 143: 76 in thoracic and 67 in lumbar. Mean operation time was 4 hours, 31 minutes with average blood loss of 2333 mL. The deformity correction was 61.9% in the coronal plane and 45.2 degrees in the sagittal plane. Complications were encountered in 24 patients: 2 complete cord injuries in severe adult scoliosis and thoracic kyphosis patient who had significant preoperative cord compromise, 6 hematomas, 4 root injuries (all incomplete), 5 fixation failures, 2 infections, and 5 hemopneumothoraxes. CONCLUSIONS: Posterior vertebral column resection is an effective alternative for moderate to severe deformities with limited flexibility. However, it is a technically demanding and exhausting procedure with possible risks for major complications.

STUDY DESIGN: Review paper of outcome studies among primary care back pain patients. OBJECTIVES: To determine the short-term and long-term pain and functional outcomes of patients with back pain who are seeking treatment in primary care settings. SUMMARY OF BACKGROUND DATA: Back pain has been viewed as running either an acute or a chronic course, but most patients experience recurrent back pain. This review summarizes outcome studies in light of the episodic course of back pain. METHODS: Studies reporting pain and functional outcome data for consecutive primary care patients with back pain were reviewed. RESULTS: Back pain among primary care patients typically is a recurrent condition for which definitions of acute and chronic pain based on a single episode are inadequate. Because a majority of patients experience recurrences, describing only the outcome of the initial back pain episode may convey a more favorable picture of long-term outcome than warranted. For the short-term follow-up evaluation, most patients improve considerably during the first 4 weeks after seeking treatment. Sixty-six percent to 75% continue to experience at least mild back pain 1 month after seeking care. At 1 month, approximately 33% report continuing pain of at least moderate intensity, whereas 20-25% report substantial activity limitations. For the long-term follow-up (1 year or more) period, approximately 33% report intermittent or persistent pain of at least moderate intensity, one in seven continue to report back pain of severe intensity, and one in five report substantial activity limitations. CONCLUSION: Results from existing studies suggest that back pain among primary care patients typically runs a recurrent course characterized by variation and change, rather than an acute, self-limiting course.

Reactive oxygen species (ROS) are free radicals produced in biological systems that are involved in various degenerative brain diseases. The present study tests the hypothesis that ROS also play an important role in neuropathic pain. In the rat spinal nerve ligation (SNL) model of neuropathic pain, mechanical allodynia develops fully 3 days after nerve ligation and persists for many weeks. Systemic injection of a ROS scavenger, phenyl-N-tert-butylnitrone (PBN), relieves SNL-induced mechanical allodynia in a dose-dependent manner. Repeated injections cause no development of tolerance or no loss of potency. Preemptive treatment with PBN is also effective in preventing full development of neuropathic pain behavior. Systemic injection was mimicked by intrathecal injection with a little less efficacy, while intracerebroventricular administration produced a much smaller effect. These data suggest that PBN exerts its anti-allodynic action mainly by spinal mechanisms. Systemic treatment with other spin-trap reagents, 5,5-dimethylpyrroline-N-oxide and nitrosobenzene, showed similar analgesic effects, suggesting that ROS are critically involved in the development and maintenance of neuropathic pain. Thus this study suggests that systemic administration of non-toxic doses of free radical scavengers could be useful for treatment of neuropathic pain.

Approximately 30% of postmenopausal white women in the United States have osteoporosis, and 16% have osteoporosis of the lumbar spine in particular. Bone density of the spine is positively associated with greater height and weight, older age at menopause, a history of arthritis, more physical activity, moderate use of alcoholic beverages, diuretic treatment, and current estrogen replacement therapy, whereas later age at menarche and a maternal history of fracture are associated with lower levels of density. Low bone density leads to an increased risk of osteoporotic fractures. Fracture risk also increase with age. Vertebral fractures affect approximately 25% of postmenopausal women, although the exact figure depends on the definition used. Recent data show that vertebral fracture rates are as great in men as in women but, because women live longer, the lifetime risk of a vertebral fracture from age 50 onward is 16% in white women and only 5% in white men. Fracture rates are less in most nonwhite populations, but vertebral fractures are as common in Asian women as in those of European heritage. Other risk factors for vertebral fractures are less clear but include hypogonadism and secondary osteoporosis; obesity is protective of fractures as it is of bone loss. Compared with hip fractures, vertebral fractures are less disabling and less expensive, costing approximately $746 million in the United States in 1995. However, they have a substantial negative impact on the patient's function and quality of life. The adverse effects of osteoporotic fractures are likely to increase in the future with the growing number of elderly people.

Wine is one of the most consumed beverages around the world. It is composed of alcohols, sugars, acids, minerals, proteins and other compounds, such as organic acids and volatile and phenolic compounds (also called polyphenols). Polyphenols have been shown to be highly related to both (i) wine quality (color, flavor, and taste) and (ii) health-promoting properties (antioxidant and cardioprotective among others). Polyphenols can be grouped into two big families: (i) Flavonoids, including anthocyanidins, flavonols, flavanols, hydrolysable and condensed tannins, flavanones, flavones and chalcones; and (ii) Non-flavonoids, including hydroxycinnamic acids, hydroxybenzoic acids, stilbenes, tyrosol and hydroxytyrosol. Each group affects in some way the different properties of wine to a greater or a lesser extent. For that reason, the phenolic composition can be managed to obtain singular wines with specific, desirable characteristics. The current review presents a summary of the ways in which the phenolic composition of wine can be modulated, including (a) invariable factors such as variety, field management or climatic conditions; (b) pre-fermentative strategies such as maceration, thermovinification and pulsed electric field; (c) fermentative strategies such as the use of different yeasts and bacteria; and (d) post-fermentative strategies such as maceration, fining agents and aging. Finally, the different extraction methods and analytical techniques used for polyphenol detection and quantification have been also reviewed.

OBJECTIVE: Sports medicine clinicians commonly use multiple tests when evaluating patients with concussion. The specific tests vary but often include symptom inventories, posturography, and neurocognitive examinations. The sensitivity of these tests to concussion is vital in reducing the risk for additional injury by prematurely returning an athlete to play. Our study investigated the sensitivity of concussion-related symptoms, a postural control evaluation, and neurocognitive functioning in concussed collegiate athletes. METHODS: From 1998 to 2005, all high-risk athletes completed a baseline concussion-assessment battery that consisted of a self-reported symptom inventory, a postural control evaluation, and a neurocognitive assessment. Postconcussion assessments were administered within 24 hours of injury to 75 athletes who had physician-diagnosed concussion. Individual tests and the complete battery were evaluated for sensitivity to concussion. RESULTS: The computerized Immediate Post-Concussion Assessment and Cognitive Testing and HeadMinder Concussion Resolution Index (neurocognitive tests) were the most sensitive to concussion (79.2 and 78.6%, respectively). These tests were followed by self-reported symptoms (68.0%), the postural control evaluation (61.9%), and a brief pencil-and-paper assessment of neurocognitive function (43.5%). When the complete battery was assessed, sensitivity exceeded 90%. CONCLUSION: Currently recommended concussion-assessment batteries accurately identified decrements in one or more areas in most of the athletes with concussion. These findings support previous recommendations that sports-related concussion should be approached through a multifaceted assessment with components focusing on distinct aspects of the athlete's function.

AIMS AND OBJECTIVES: To evaluate at what age parous and nonparous women were diagnosed with breast cancer. Factors taken into account for parous women were whether they had breastfed their children, and if so, the length of the lactation period. Other factors considered for both groups were obesity, family histories of cancer, smoking habits and alcohol consumption. BACKGROUND: Breast cancer is the most common form of cancer in younger women in Western countries. Its growing incidence as well as the increasingly early age of diagnosis led us to carefully analyse its possible causes and the preventive measures to be taken. This is a particularly important goal in epidemiological research. DESIGN: A retrospective study of the clinical histories of patients diagnosed with breast cancer at the San Cecilio University Hospital in Granada (Spain). METHODS: In this study, we analysed 504 medical records of female patients, 19-91 years of age, who had been diagnosed and treated for breast cancer from 2004-2009 at the San Cecilio University Hospital in Granada (Spain). Relevant data (age of diagnosis, period of lactation, family history of cancer, obesity, alcohol consumption and smoking habits) were collected from the clinical histories of each patient and analysed. A conditional inference tree was used to relate the age of diagnosis to smoking habits and the length of the lactation period. RESULTS: The conditional inference tree identified significant differences between the age of the patients at breast cancer diagnosis, smoking habits (p < 0·001) and lactation period if the subjects had breastfed their children for more than six months (p = 0·006), regardless of whether they had a family history of cancer. CONCLUSIONS: Our study concluded that breastfeeding for over six months not only provides children with numerous health benefits, but also protects mothers from breast cancer when the mothers are nonsmokers. RELEVANCE TO CLINICAL PRACTICE: Nurses play a crucial role in encouraging new mothers to breastfeed their children, and this helps to prevent breast cancer.

We investigated short-term effects (up to 24 h) of air exposure and confinement, and long-term effects (up to 11 days) of confinement, to elucidate signalling pathways in the stress response of gilthead sea bream Sparus aurata L. Plasma glucose and lactate were taken as indicators of sympathetic activation, and alpha-melanocyte stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH) and cortisol as indicators of activation of the brain-pituitary-interrenal (BPI) axis. Air exposure for 3 min resulted, within 30 min, in an increase in plasma concentrations of cortisol, alpha-MSH, glucose, lactate, osmolality and plasma Na, Cl and Mg. Plasma ACTH and beta-endorphin and plasma K, Ca and P did not change. We conclude that air exposure mainly activates the brain-sympathetic-chromaffin cell (BSC) axis. In fish confined at a density of 70 kg/m(3) (compared with 4 kg/m(3) in controls), cortisol, ACTH and alpha-MSH increased within 1 h, indicating activation of the BPI axis. Plasma glucose, Na, Cl and Mg increased with an 8 h delay compared with the response to air exposure. No changes in plasma lactate, osmolality, K, Ca and P were observed. Long-term confinement induced a biphasic cortisol response with peaks at 1 h and at 2 and 3 days. A gradual increase in plasma beta-endorphin concentrations peaked at 7 days; the concentration of alpha-MSH increased rapidly within 1 h and then declined to control values 4 days after the onset of confinement. No changes in ACTH were detected. Our data provide evidence that a stressor-specific activation of the BSC and BPI axes may occur in Sparus aurata.

Acceptance of chronic pain is emerging as an important concept in understanding ways that chronic pain sufferers can remain engaged with valued aspects of life. Recent studies have relied heavily on cross-sectional investigations at a single time point. The present study sought to prospectively investigate relations between acceptance of chronic pain and patient functioning. A sample of adults referred for interdisciplinary treatment of severe and disabling chronic pain was assessed twice, an average of 3.9 months apart. Results showed that pain and acceptance were largely unrelated. Pain at Time 2 was weakly related to measures of functioning at Time 2. On the other hand, acceptance at Time 1 was consistently related to patient functioning at Time 2. Those patients who reported greater acceptance at Time 1 reported better emotional, social, and physical functioning, less medication consumption, and better work status at Time 2. These data suggest that willingness to have pain, and to engage in activity regardless of pain, can lead to healthy functioning for patients with chronic pain. Treatment outcome and process studies may demonstrate the potential for acceptance-based clinical methods for chronic pain management.

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.

PURPOSE: Any of several conditions can cause asthenopia. The purpose of this study was to determine whether the particular sensations or their location vary dependent on the symptom-inducing condition. METHODS: Twenty subjects with good vision performed eight reading tasks in random order during different conditions. Each condition used different stimuli to induce asthenopia. The eight conditions were mixed astigmatism, close viewing distance, upward gaze, dry eyes, lens flipper, small font, glare, and flickering light. Subjects were asked to read until attaining a level of discomfort self-defined as "barely tolerable." After each task, subjects rated the magnitude of several symptom descriptors (burning, ache, strain, irritation, tearing, blurred vision, double vision, dryness, and headache) and their location. RESULTS: Analysis of variance with repeated measures was used to determine that all of the individual symptom sensation measures (except blur) were significantly related (p values ranged from 0.003 to <0.0001) to the inducing condition. Principal factor analysis with orthogonal varimax rotation was used to test symptom by condition relationships and determined two latent factors, designated external and internal symptom factors (ESF and ISF), that related symptoms to inducing condition. The ESF pattern comprises burning, irritation, tearing, and dryness located in the front and bottom of the eye. ESF is caused by holding the eyelid open, glare, up gaze, small font, and flickering. ESF seems highly related to dry-eye symptoms. The ISF pattern comprises ache, strain, and headache located behind the eyes. ISF is caused by the close viewing distance, lens flipper, and mixed astigmatism conditions and is likely related to accommodative and vergence stress. CONCLUSIONS: Symptom descriptors and locations were able to distinguish discomfort on the basis of causative condition. Results support two different symptom constellations and, hence, at least two different afferent pathways for symptoms of asthenopia.

Objective: To assess whether adolescent obesity is associated with risk for development of major depressive disorder (MDD) or anxiety disorder. Obesity has been linked to psychosocial difficulties among youth. Methods: Analysis of a prospective community-based cohort originally from upstate New York, assessed four times over 20 years. Participants (n = 776) were 9 to 18 years old in 1983; subsequent assessments took place in 1985 to 1986 (n = 775), 1991 to 1994 (n = 776), and 2001 to 2003 (n = 661). Using Cox proportional hazards analysis, we evaluated the association of adolescent (age range, 12–17.99 years) weight status with risk for subsequent MDD or anxiety disorder (assessed at each wave by structured diagnostic interviews) in males and females. A total of 701 participants were not missing data on adolescent weight status and had ≥1 subsequent assessments. MDD and anxiety disorder analyses included 674 and 559 participants (free of current or previous MDD or anxiety disorder), respectively. Adolescent obesity was defined as body mass index above the age- and gender-specific 95th percentile of the Centers for Disease Control and Prevention growth reference. Results: Adolescent obesity in females predicted an increased risk for subsequent MDD (adjusted hazard ratio (HR) = 3.9; 95% confidence interval (CI) = 1.3, 11.8) and for anxiety disorder (HR = 3.8; CI = 1.3, 11.3). Adolescent obesity in males was not statistically significantly associated with risk for MDD (HR = 1.5; CI = 0.5, 3.5) or anxiety disorder (HR = 0.7; CI = 0.2, 2.9). Conclusion: Females obese as adolescents may be at increased risk for development of depression or anxiety disorders. BMI = body mass index; CDC = Centers for Disease Control and Prevention; CI = confidence interval; CIC = Children in the Community Study; DSM = Diagnostic and Statistical Manual of Mental Disorders; DISC = Diagnostic Interview Schedule for Children; HR = hazard ratio; SCID-IV = Structured Clinical Interview for DSM-IV Disorders; SD = standard deviation; SES = socioeconomic status.

STUDY DESIGN: Prospective case series. OBJECTIVE: To determine the outcome of patients with chronic low back pain whose symptoms did not improve with aggressive nonoperative care and who chose (intradiscal electrothermal anuloplasty) IDET as an alternative to chronic pain management or interbody fusion surgery. SUMMARY OF BACKGROUND DATA: Patients with unremitting chronic discogenic low back pain are faced with the choice of long-term pain management or fusion surgery. Intradiscal electrothermal anuloplasty (IDET) was developed as an alternative minimally invasive treatment. MATERIALS AND METHODS: Sixty-two patients from the author's practice who had chronic low back pain unresponsive to nonoperative care, no evidence of compressive radiculopathy, and concordant pain reproduction at one or more disc levels on provocative discography were enrolled in the study. Visual analog scale (VAS) pain scores and Short Form (SF)-36 Health Status Questionnaire Physical Function subscale and SF-36 Bodily Pain subscale scores were assessed at baseline and at least 1 year later. RESULTS: Mean follow-up was 16 months, and mean preoperative duration of symptoms was 60 months. Baseline and follow-up outcome measures demonstrated a mean change in VAS score of 3.0 (P < 0.001), mean change in SF-36 physical function of 20 (P < 0.001), and mean change in SF-36 bodily pain of 17 (P < 0.001). Symptoms improved in 44 (71%) of 62 of the study group on the SF-36 physical function subscale, in 46 (74%) of 62 on the SF-36 Bodily Pain subscale, and in 44 (71%) of 62 on the VAS scores. Twelve (19%) of 62 of the patients did not show improvement on any scale. CONCLUSION: A cohort of patients with chronic unremitting low back pain of discogenic origin whose symptoms had failed to improve with aggressive nonoperative care demonstrated a statistically significant and clinically meaningful improvement on the SF-36 and the VAS scores at a minimum follow-up of 1 year after IDET. The positive results should be validated with placebo-controlled randomized trials and studies that compare IDET with alternative treatments.-

In this article, we meta-analytically examined the efficacy of biofeedback (BFB) in treating migraine. A computerized literature search of the databases Medline, PsycInfo, Psyndex and the Cochrane library, enhanced by a hand search, identified 86 outcome studies. A total of 55 studies, including randomized controlled trials as well as pre-post trials, met our inclusion criteria and were integrated. A medium effect size (d =0.58, 95% CI=0.52, 0.64) resulted for all BFB interventions and proved stable over an average follow-up phase of 17 months. Also, BFB was more effective than control conditions. Frequency of migraine attacks and perceived self-efficacy demonstrated the strongest improvements. Blood-volume-pulse feedback yielded higher effect sizes than peripheral skin temperature feedback and electromyography feedback. Moderator analyses revealed BFB in combination with home training to be more effective than therapies without home training. The influence of the meta-analytical methods on the effect sizes was systematically explored and the results proved to be robust across different methods of effect size calculation. Furthermore, there was no substantial relation between the validity of the integrated studies and the direct treatment effects. Finally, an intention-to-treat analysis showed that the treatment effects remained stable, even when drop-outs were considered as nonresponders.

STUDY DESIGN: Retrospective review of a prospectively collected, multicenter database. OBJECTIVE: To assess rates of new neurologic deficit (NND) associated with spine surgery. SUMMARY OF BACKGROUND DATA: NND is a potential complication of spine surgery, but previously reported rates are often limited by small sample size and single-surgeon experiences. METHODS: The Scoliosis Research Society morbidity and mortality database was queried for spinal surgery cases complicated by NND from 2004 to 2007, including nerve root deficit (NRD), cauda equina deficit (CED), and spinal cord deficit (SCD). Use of neuromonitoring was assessed. Recovery was stratified as complete, partial, or none. Rates of NND were stratified based on diagnosis, age (pediatric < 21; adult ≥ 21), and surgical parameters. RESULTS: Of the 108,419 cases reported, NND was documented for 1064 (1.0%), including 662 NRDs, 74 CEDs, and 293 SCDs (deficit not specified for 35 cases). Rates of NND were calculated on the basis of diagnosis. Revision cases had a 41% higher rate of NND (1.25%) compared with primary cases (0.89%; P < 0.001). Pediatric cases had a 59% higher rate of NND (1.32%) compared with adult cases (0.83%; P < 0.001). The rate of NND for cases with implants was more than twice that for cases without implants (1.15% vs. 0.52%, P < 0.001). Neuromonitoring was used for 65% of cases, and for cases with new NRD, CED, and SCD, changes in neuromonitoring were reported in 11%, 8%, and 40%, respectively. The respective percentages of no recovery, partial, and complete recovery for NRD were 4.7%, 46.8%, and 47.1%, respectively; for CED were 9.6%, 45.2%, and 45.2%, respectively; and for SCD were 10.6%, 43%, and 45.7%, respectively. CONCLUSION: Our data demonstrate that, even among skilled spinal deformity surgeons, new neurologic deficits are inherent potential complications of spine surgery. These data provide general benchmark rates for NND with spine surgery as a basis for patient counseling and for ongoing efforts to improve safety of care.

Over a 24 month period, 30 patients with proximal tibia fractures who were reviewed consecutively were treated by nonreamed, statically locked, intramedullary nailing. There were 16 open, 13 segmental, and 7 comminuted fractures (Winquist III, IV). The average distance from the fracture to the proximal locking screws was 24 mm (range, 0-65 mm). All procedures were performed while the patient's affected leg was on a radiolucent table without traction. The last 25 fractures were nailed using a partial (2/3) medial parapatellar incision while the leg was semiextended. This approach allowed the patella to be subluxed laterally availing the trochlear groove for use as a conduit for nail placement. Using only 15 degrees knee flexion eliminated the extension force of the quadriceps on the proximal fragment, which otherwise would have tended to cause anterior angulation at the fracture site. In the first 5 patients, the average anterior angulation was 8 degrees (range, 5 degrees-15 degrees). Of the 25 patients who were treated while in the semiextended position, none had more than 5 degrees anterior angulation and 19 had no anterior angulation. Fractures of 3 of the 25 patients had greater than 5 degrees angulation in the coronal plane, 2 of which were nailed in the semiextended position. This technique greatly facilitates intramedullary nailing of proximal tibia fractures.