Acute rotenone poisoning: A scoping review.

Context: Rotenone is a toxic chemical found in various plants, including some used as food. Rotenone poisoning can be fatal and there is no antidote. Mechanistically, rotenone inhibits mitochondrial complex I, leading to reduced ATP production, compensatory glycolytic upregulation and secondary lactate production, and oxidative stress. Our literature review examined acute rotenone poisoning in humans, including exposure scenarios, clinical presentations, and treatments. Methods: We searched five databases for relevant literature from database inception through the search date: July 12, 2022, pairing controlled vocabulary and keywords for "rotenone" with terms relating to human exposures and outcomes, such as "ingestion," "exposure," and "poisoning." We included all peer-reviewed reports found using the search terms where the full English text was available. Data abstracted included the number, age, weight, and sex of the exposed person(s), country where exposure happened, exposure scenario, ingestion context, estimated dose, clinical features, whether hospitalization occurred, treatments, and outcomes. Results: After removing non-qualifying sources from 2,631 publications, we identified 11 case reports describing 18 victims, 15 of whom were hospitalized and five died. Most cases occurred in private quarters where victims unknowingly consumed rotenone-containing plants. Vomiting and metabolic acidosis occurred most commonly. Some patients exhibited impaired cardiopulmonary function. Supportive treatment addressed symptoms and included gastric lavage and/or activated charcoal to remove rotenone from the stomach, vasopressors for hypotension, mechanical ventilation for respiratory insufficiency, and sodium bicarbonate for acidosis. Some patients received N-acetylcysteine to counter oxidative stress. Conclusions: Rotenone poisoning, though rare, can be fatal. Exposure prevention is impractical since rotenone is found in some plants used as food or pesticides. Cases may be under-diagnosed because symptoms are non-specific and under-reported in English-language journals since most cases occurred in non-English speaking countries. Treatments are supportive. Exploring antioxidant therapy in animal models of rotenone poisoning may be indicated considering rotenone's mechanism of toxicity.

The Antioxidant/Nitric Oxide-Quenching Agent Cobinamide Prevents Aortic Disease in a Mouse Model of Marfan Syndrome.

Major pathologic changes in the proximal aorta underlie the life-threatening aortic aneurysms and dissections in Marfan Syndrome; current treatments delay aneurysm development without addressing the primary pathology. Because excess oxidative stress and nitric oxide/protein kinase G signaling likely contribute to the aortopathy, we hypothesized that cobinamide, a strong antioxidant that can attenuate nitric oxide signaling, could be uniquely suited to prevent aortic disease. In a well-characterized mouse model of Marfan Syndrome, cobinamide dramatically reduced elastin breaks, prevented excess collagen deposition and smooth muscle cell apoptosis, and blocked DNA, lipid, and protein oxidation and excess nitric oxide/protein kinase G signaling in the ascending aorta. Consistent with preventing pathologic changes, cobinamide diminished aortic root dilation without affecting blood pressure. Cobinamide exhibited excellent safety and pharmacokinetic profiles indicating it could be a practical treatment. We conclude that cobinamide deserves further study as a disease-modifying treatment of Marfan Syndrome.

The vitamin B12 analog cobinamide ameliorates azide toxicity in cells, Drosophila melanogaster, and mice.

CONTEXT: The azide anion (N3-) is highly toxic. It exists most commonly as sodium azide, which is used widely and is readily available, raising the potential for occupational incidents and use as a weapon of mass destruction. Azide-poisoned patients present with vomiting, seizures, hypotension, metabolic acidosis, and coma; death can occur. No specific azide antidote exists, with treatment being solely supportive. Azide inhibits mitochondrial cytochrome c oxidase and is likely oxidized to nitric oxide in vivo. Cytochrome c oxidase inhibition depletes intracellular adenosine triphosphate and increases oxidative stress, while increased nitric oxide causes hypotension and exacerbates oxidative damage. Here, we tested whether the cobalamin (vitamin B12) analog cobinamide, a strong and versatile antioxidant that also neutralizes nitric oxide, can reverse azide toxicity in mammalian cells, Drosophila melanogaster, and mice. RESULTS: We found cobinamide bound azide with a moderate affinity (Ka 2.87 × 105 M-1). Yet, cobinamide improved growth, increased intracellular adenosine triphosphate, and reduced apoptosis and malondialdehyde, a marker of oxidative stress, in azide-exposed cells. Cobinamide rescued Drosophila melanogaster and mice from lethal exposure to azide and was more effective than hydroxocobalamin. Azide likely generated nitric oxide in the mice, as evidenced by increased serum nitrite and nitrate, and reduced blood pressure and peripheral body temperature in the animals; the reduced temperature was likely due to reflex vasoconstriction in response to the hypotension. Cobinamide improved recovery of both blood pressure and body temperature. CONCLUSION: We conclude cobinamide likely acted by neutralizing both oxidative stress and nitric oxide, and that it should be given further consideration as an azide antidote.

Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice.

Increased oxidative stress underlies a variety of diseases, including diabetes. Here, we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multifaceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M-1 s-1, respectively, for cobinamide with the cobalt in the +2 oxidation state. Cobinamide with the cobalt in the +3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M-1 s-1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals' drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress.

COVID-19 threatens faculty diversity: postdoctoral scholars call for action.

Despite substantial investment and effort by federal agencies and institutions to improve the diversity of the professoriate, progress is excruciatingly slow. One program that aims to enhance faculty diversity is the Institutional Research and Academic Career Development Award (IRACDA) funded by the National Institutes of Health/National Institute of General Medical Sciences. IRACDA supports the training of a diverse cohort of postdoctoral scholars who will seek academic research and teaching careers. The San Diego IRACDA program has trained 109 postdoctoral scholars since its inception in 2003; 59% are women and 63% are underrepresented (UR) Black/African-American, Latinx/Mexican-American, and Indigenous scientists. Sixty-four percent obtained tenure-track faculty positions, including a substantial 32% at research-intensive institutions. However, the COVID-19 pandemic crisis threatens to upend IRACDA efforts to improve faculty diversity, and academia is at risk of losing a generation of diverse, talented scholars. Here, a group of San Diego IRACDA postdoctoral scholars reflects on these issues and discusses recommendations to enhance the retention of UR scientists to avoid a "lost generation" of promising UR faculty scholars.

Methyl mercaptan gas: mechanisms of toxicity and demonstration of the effectiveness of cobinamide as an antidote in mice and rabbits.

CONTEXT: Methyl mercaptan (CH3SH) is a colorless, toxic gas with potential for occupational exposure and used as a weapon of mass destruction. Inhalation at high concentrations can result in dyspnea, hypoventilation, seizures, and death. No specific methyl mercaptan antidote exists, highlighting a critical need for such an agent. Here, we investigated the mechanism of CH3SH toxicity, and rescue from CH3SH poisoning by the vitamin B12 analog cobinamide, in mammalian cells. We also developed lethal CH3SH inhalation models in mice and rabbits, and tested the efficacy of intramuscular injection of cobinamide as a CH3SH antidote. RESULTS: We found that cobinamide binds to CH3SH (Kd = 84 µM), and improved growth of cells exposed to CH3SH. CH3SH reduced cellular oxygen consumption and intracellular ATP content and activated the stress protein c-Jun N-terminal kinase (JNK); cobinamide reversed these changes. A single intramuscular injection of cobinamide (20 mg/kg) rescued 6 of 6 mice exposed to a lethal dose of CH3SH gas, while all six saline-treated mice died (p = 0.0013). In rabbits exposed to CH3SH gas, 11 of 12 animals (92%) treated with two intramuscular injections of cobinamide (50 mg/kg each) survived, while only 2 of 12 animals (17%) treated with saline survived (p = 0.001). CONCLUSION: We conclude that cobinamide could potentially serve as a CH3SH antidote.

Sodium azide poisoning: a narrative review.

CONTEXT: Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies. METHODS: We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities. RESULTS: We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients. CONCLUSIONS: Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.

Perioperative Factors Influencing Postoperative Satisfaction After Lateral Access Surgery for Degenerative Lumbar Spondylolisthesis.

BACKGROUND: Lateral access surgery (LAS) for lumbar degenerative spondylolisthesis is a minimally invasive lumbar fusion technique which has been gaining increasing popularity in the recent years. This study aims to identify perioperative factors that influence postoperative satisfaction after LAS for lumbar degenerative spondylolisthesis. METHODS: From August 2010 to November 2014, 52 patients with lumbar degenerative conditions (16 male: 36 female, mean age 64.0 ± 8.7 years) were prospectively recruited and underwent LAS by a single surgeon. All patients were assessed preoperatively and 2 years postoperatively with Numerical Pain Rating Scale (NPRS), Oswestry Disability Index, Short-Form 36 (SF-36) scores, North American Spine Society score for neurogenic symptoms, patient satisfaction, and expectation fulfillment. Cobb angles, global lumbar lordosis, disc heights, adjacent disc heights, fusion, and subsidence were rates assessed. Multiple linear regression performed with satisfaction as dependent variable to identify predictive independent variables. RESULTS: Lower preoperative SF-36 general health scores (P = .03), higher NPRS leg pain scores (P = .04), and longer surgical duration (P = .02) were significant predictors of lower satisfaction (P < .05). NPRS back and leg pain decreased by 80.3 and 83.0%, respectively. Oswestry Disability Index and North American Spine Society score for neurogenic symptoms improved by 76.2 and 75.9%, respectively. Ninety percent of patients reported excellent/good satisfaction. Significant correction and maintenance of Cobb and global lumbar lordosis angles were achieved. There was significant increase in disc heights postoperatively (P = .05) and no significant difference in adjacent disc heights at 2 years (P > .05). Ninety-eight percent of patients achieved Bridwell Fusion Grade 1, and 5.8% had Marchi Grade 3 subsidence. CONCLUSIONS: Lower preoperative SF-36 general health, higher NPRS leg pain, and longer surgical duration are predictors of lower satisfaction in patients undergoing LAS for lumbar degenerative spondylolisthesis. LEVEL OF EVIDENCE: III. CLINICAL RELEVANCE: Identifying preoperative predictors for postoperative clinical outcome can assist clinicians in patient education prior to operation.

The Diagnostic Value of Magnetic Resonance Imaging in Identifying Unsuspected Malignancy in Patients Undergoing Percutaneous Vertebral Augmentation for Vertebral Compression Fractures.

BACKGROUND: The aim of this study was to identify the rate of unsuspected malignancy in vertebral compression fractures (VCFs) treated with percutaneous vertebral augmentation procedures (PVAPs). METHODS: From 2004-2015, 410 patients with VCFs underwent PVAPs with biopsy in a single tertiary hospital. All patients had preoperative magnetic resonance imaging (MRI) read by consultant radiologists and reviewed by the performing surgeon prior to PVAPs. All procedures were performed by fellowship-trained spine surgeons. A patient was considered to have an unsuspected malignancy if preoperative MRI was negative for malignancy but histology from the operative biopsy was positive. RESULTS: A total of 44 of 45 patients (97.8%) were identified to have malignancy on preoperative MRI. One patient had a negative MRI but positive biopsy (myeloma). This patient also had a positive myeloma panel. A total of 41 of 44 patients with suspicious MRI preoperatively had a history of malignancy with histology consistent with metastatic spread from the known primary. Two patients had a new diagnosis of malignancy (1 breast carcinoma, 1 metastatic cancer likely of breast or gastrointestinal origin). Younger patients were more likely to have a VCF due to malignancy (odds ratio, 28.33 in age < 60 years). CONCLUSIONS: Almost 98% of patients with malignancy (44 of 45 patients) could be successfully identified with a preoperative MRI. The addition of a myeloma panel to MRI identified all patients with malignancies prior to PVAP in our study. We recommend MRI and myeloma panel for all patients with VCFs to be treated with PVAPs. For patients who undergo a PVAP, routine biopsy should be performed.

Poor Baseline Mental Health Does Not Influence Improvement in Patient-reported Outcomes, Satisfaction, and Return to Work Two Years After Single-level Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study using prospectively collected registry data. OBJECTIVE: The authors examine the influence of preoperative mental health on outcomes after anterior cervical discectomy and fusion (ACDF) and determine the impact of ACDF on postoperative mental health. SUMMARY OF BACKGROUND DATA: While studies have reported a negative correlation between preoperative mental health and outcomes following lumbar spine surgery, the influence on outcomes following cervical spine surgery remains relatively understudied. METHODS: Prospectively collected registry data of 104 patients who underwent single-level ACDF for cervical spondylotic myelopathy were reviewed. Patients were dichotomized into top and bottom halves based on preoperative SF-36 MCS (Mental Component Summary) using a cutoff of 48. Outcomes assessed were visual analogue scale for neck pain, arm pain, AAOS Neck Pain and Disability, Neurogenic Symptoms, Neck Disability Index, Short-Form 36, Japanese Orthopaedic Association myelopathy score, return to work, return to function, satisfaction and expectation fulfilment up to 2 years postoperatively. RESULTS: The preoperative MCS was 37.5 ±â€Š8.1 and 57.4 ±â€Š6.3 in the Low and High MCS groups respectively (P < 0.001). The Low MCS group had poorer preoperative scores (P < 0.05). There was no significant difference in length of stay or comorbidities (P > 0.05). The High MCS group had less neck pain (P = 0.002) and showed a trend towards lower Neck Disability Index (P = 0.062) at 2 years. The Low MCS group demonstrated greater improvement in Japanese Orthopaedic Association (P = 0.007) and similar improvement in other scores (P > 0.05). There was no significant difference in proportion that achieved minimal clinically important difference for each score (P > 0.05). Both groups had similar rates of return to work, return to function, expectation fulfilment, and satisfaction (P > 0.05). Lower preoperative MCS was predictive of greater improvement in MCS (r = -0.477, P < 0.001). CONCLUSION: Despite relatively greater pain and disability at 2 years, patients with poor baseline mental health experienced similar improvement in clinical outcomes, return to work, and satisfaction rates. LEVEL OF EVIDENCE: 3.

Poorer Fusion Outcomes in Diabetic Cervical Spondylotic Myelopathy Patients Undergoing Single-level Anterior Cervical Discectomy and Fusion Does Not Compromise Functional Outcomes and Quality of Life.

STUDY DESIGN: Retrospective matched pair cohort study using prospectively collected registry data. OBJECTIVES: The aim of this study was to determine whether patients with DM have poorer patient-reported outcomes and poorer fusion rates after undergoing a single-level anterior cervical discectomy and fusion (ACDF) for cervical myelopathy. SUMMARY OF BACKGROUND DATA: ACDF remains the most common procedure in the treatment of cervical spondylotic myelopathy (CSM); however, there is a paucity of literature with regards to patient-reported outcome measures (PROMs), health-related quality-of-life (HRQOL) scores, and fusion rates post-ACDF in diabetic patients with CSM. METHODS: From 2002 to 2012, 29 diabetic patients were matched with 29 nondiabetic controls. Patient demographics, perioperative data, and validated spine-specific scores including the Numerical Pain Rating Scale on Neck Pain and Upper Limb Pain, American Academy of Orthopaedic Surgeons (AAOS) neck pain and disability scores, AAOS Neurogenic Symptoms Score, Neck Disability Index, Japanese Orthopaedic Association Cervical Myelopathy Score, and Short Form 36 Physical/Mental Component Summaries were recorded. Fusion rates based on Bridwell grading were assessed at 2 years. RESULTS: After matching, there were no significant preoperative differences in patient demographics, clinical outcomes, PROMs or HRQoL measures between the DM and control group (P > 0.05). There was no difference in either length of hospital stay (P = 0.92) or length of surgery (P = 0.92) between the two groups. At 2 years postoperatively, there were no significant differences between validated spine-specific scores, PROMs, HRQoL scores, satisfaction rates, or fulfilment of expectations between the two groups. Significant poorer Bridwell fusion grades were noted in the DM group at 2 years postoperatively (P < 0.05). Subgroup analysis within the DM group demonstrated that glycated hemoglobin levels had no impact on functional outcomes, fulfilment of expectations, or patient satisfaction at 2 years (P > 0.05). CONCLUSION: Despite poorer fusion outcomes following single-level ACDF for symptomatic CSM, there was no significant difference in validated spine outcome scores, PROMs, HRQoL measures, or satisfaction levels when compared to nondiabetic controls at short-term follow-up. LEVEL OF EVIDENCE: 3.

CKS Proteins Promote Checkpoint Recovery by Stimulating Phosphorylation of Treslin.

CKS proteins are small (9-kDa) polypeptides that bind to a subset of the cyclin-dependent kinases. The two paralogs expressed in mammals, Cks1 and Cks2, share an overlapping function that is essential for early development. However, both proteins are frequently overexpressed in human malignancy. It has been shown that CKS protein overexpression overrides the replication stress checkpoint, promoting continued origin firing. This finding has led to the proposal that CKS protein-dependent checkpoint override allows premalignant cells to evade oncogene stress barriers, providing a causal link to oncogenesis. Here, we provide mechanistic insight into how overexpression of CKS proteins promotes override of the replication stress checkpoint. We show that CKS proteins greatly enhance the ability of Cdk2 to phosphorylate the key replication initiation protein treslin in vitro Furthermore, stimulation of treslin phosphorylation does not occur by the canonical adapter mechanism demonstrated for other substrates, as cyclin-dependent kinase (CDK) binding-defective mutants are capable of stimulating treslin phosphorylation. This effect is recapitulated in vivo, where silencing of Cks1 and Cks2 decreases treslin phosphorylation, and overexpression of wild-type or CDK binding-defective Cks2 prevents checkpoint-dependent dephosphorylation of treslin. Finally, we provide evidence that the role of CKS protein-dependent checkpoint override involves recovery from checkpoint-mediated arrest of DNA replication.

Strategy for Sustaining Cancer Education Services for Underserved Communities.

Innovative strategies are needed to generate resources to replicate and sustain proven, community-based health promotion programs. Authors describe how civic-minded university students can conduct such programs while simultaneously gaining skills that make them competitive graduate school applicants.

CKS protein overexpression renders tumors susceptible to a chemotherapeutic strategy that protects normal tissues.

The cyclin-dependent kinase-interacting proteins Cyclin-dependent Kinase Subunit 1 and 2 (CKS1 and 2) are frequently overexpressed in cancer and linked to increased aggressiveness and poor prognoses. We previously showed that CKS protein overexpression overrides the replication stress checkpoint activated by oncoproteins. Since CKS overexpression and oncoprotein activation/overexpression are often observed in the same tumors, we have hypothesized that CKS-mediated checkpoint override could enhance the ability of premalignant cells experiencing oncoprotein-induced replication stress to expand. This tumor advantage, however, could represent a vulnerability to exploit therapeutically. Here, we first show in vitro that CKS protein overexpression selectively sensitizes tumor-derived cell lines to nucleoside analog-mediated toxicity under replication stress conditions. A treatment combination of the nucleoside analog gemcitabine and an agent that induces replication stress (thymidine or methotrexate) resulted in selective targeting of CKS protein-overexpressing tumor-derived cells while protecting proliferative cells with low CKS protein levels from gemcitabine toxicity. We validated this strategy in vivo and observed that Cks2-overexpressing mammary tumors in nude mice were selectively sensitized to gemcitabine under conditions of methotrexate-induced replication stress. These results suggest that high CKS expression might be useful as a biomarker to identify subgroups of cancer patients who might benefit from the described therapeutic approach.

The Asian Grocery Store-Based Cancer Education Program: Creating New Education Modules.

Operating since 1994, the UCSD Moores Cancer Center's Asian Grocery Store-Based Cancer Education Program (the Program) is a proven and sustainable strategy for disseminating cancer and poison control information to Asian and Pacific Islander (API) communities. This paper describes the process taken to identify health topics that can be readily addressed within the Program's infrastructure and reports results of the pilot testing of the educational module that was developed by following that process. The development of each new module is guided by the Health Belief Model and the Tipping Point Model. The process starts with the selection of a health topic demonstrating pressing need and treatment options in the API community. Then, using the Pareto principle, reasonably modifiable risk factors are chosen to be addressed in the module. "Sticky messaging" for the modifiable risk factors is developed to package the health information as memorable and transmissible calls-to-action. Finally, grocery store outreaches were used to pilot test the new module to assess its effectiveness at facilitating health care information to API community members. By adhering to the steps described in this paper, the authors were able to: (1) select liver cancer as a pressing API health issue that could be positively impacted by the Program; (2) identify reasonably modifiable risk factors for the chosen health issue; (3) generate compelling call-to-action messages to decrease risk of exposure; and (4) demonstrate the cultural and linguistic alignment of the liver cancer control module. The development and testing of new health education modules follow a methodical process guided by scientific principles. Understanding and employing the elements of an existing evidence-based and sustainable health education program can increase the likelihood of success in addressing the health needs of the API community.

Comparison of Clinical Outcomes and Radiographic Measurements in 4 Different Treatment Modalities for Osteoporotic Compression Fractures: Retrospective Analysis.

STUDY DESIGN: We conducted a retrospective analysis of a prospectively collected database in a tertiary hospital over 10 years. OBJECTIVE: Treatment for vertebral compression fractures remains an area of controversy with respect to timing and type of surgical management. We analyzed the clinical outcomes and radiographic measurements of 4 different modalities of treatment for these fractures. SUMMARY OF BACKGROUND DATA: From 2001 to 2011, we analyzed a total of 363 patients after failure of 30 days of conservative management. These patients were then further managed either conservatively or with vertebroplasty, balloon kyphoplasty, or sky bone expander. Outcomes were assessed by using self-report measures: Visual Analog Score; functional measures: Oswestry Disability Index and Short-Form 36; and physiological measures: preoperative and postoperative radiographs. METHODS: The outcome measures were assessed for 6 months for those treated conservatively and up till 2 years for those treated surgically. Radiographic measurements of the spine were correlated with the clinical outcomes. RESULTS: A total of 62 patients (12.1%) were treated conservatively, 148 (40.8%) with vertebroplasty, 97 (26.7%) with balloon kyphoplasty, and 56 (15.4%) with sky bone expander. We found significant improvements in Visual Analog Score, Oswestry Disability Index, and Short-Form-36 scores for all groups after 1-month follow-up (P<0.05), with the surgical groups demonstrating a greater improvement in pain scores after the first postoperative day (P<0.0001) when compared with the conservative group. The improvements in outcomes in those treated surgically were sustained for up to 2 years with no significant difference (P>0.05) among the surgical groups. We also found significant improvement (P<0.005) in anterior vertebral and kyphotic wedge angle after surgical intervention. CONCLUSIONS: We have shown that early surgical intervention allows for quicker pain relief compared with conservative treatment, with similar improvements in anterior vertebral height and kyphotic wedge angle between all 3 groups of surgical management.

Disseminating tobacco control information to Asians and Pacific Islanders.

The Asian Grocery Store-Based Cancer Education Program (the Program) is a proven strategy for promoting early breast cancer detection among Asian American women. The authors sought to test whether the same public health model can become an effective strategy for increasing the Asian community's awareness of the California Smokers' Helpline (the Helpline) and thereby, potentially decreasing this community's use of tobacco products. The new module, mainly staffed by four well-trained, volunteer undergraduates, explained the risks of first- and second-hand tobacco exposure and how to access the Helpline's services. A brochure, provided in English, Chinese, Korean, and Vietnamese (the Helpline's available Asian languages), was used to guide the bicultural, bilingual students' tobacco-related discussions with shoppers. The students' repeated presence at the nine partnering Asian grocery stores served as reminders of the Helpline's availability. In its first year of operation, the student trainers reached 1,052 men and 1,419 women with tobacco cessation messages. Equally important, the participating grocery stores' managers did not object to students telling their customers to quit using the tobacco products sold in their stores. The results suggest that the Program's tobacco cessation module is a viable, community-specific, public health strategy. It is also a strategy with the potential for applications to reduce other health threats.

DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3.

The response to DNA damage, which regulates nuclear processes such as DNA repair, transcription, and cell cycle, has been studied thoroughly. However, the cytoplasmic response to DNA damage is poorly understood. Here, we demonstrate that DNA damage triggers dramatic reorganization of the Golgi, resulting in its dispersal throughout the cytoplasm. We further show that DNA-damage-induced Golgi dispersal requires GOLPH3/MYO18A/F-actin and the DNA damage protein kinase, DNA-PK. In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas overexpression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents. Identification of the DNA-damage-induced Golgi response reveals an unexpected pathway through DNA-PK, GOLPH3, and MYO18A that regulates cell survival following DNA damage.

A posttranslational modification cascade involving p38, Tip60, and PRAK mediates oncogene-induced senescence.

Oncogene-induced senescence is an important tumor-suppressing defense mechanism. However, relatively little is known about the signaling pathway mediating the senescence response. Here, we demonstrate that a multifunctional acetyltransferase, Tip60, plays an essential role in oncogenic ras-induced senescence. Further investigation reveals a cascade of posttranslational modifications involving p38, Tip60, and PRAK, three proteins that are essential for ras-induced senescence. Upon activation by ras, p38 induces the acetyltransferase activity of Tip60 through phosphorylation of Thr158; activated Tip60 in turn directly interacts with and induces the protein kinase activity of PRAK through acetylation of K364 in a manner that depends on phosphorylation of both Tip60 and PRAK by p38. These posttranslational modifications are critical for the prosenescent function of Tip60 and PRAK, respectively. These results have defined a signaling pathway that mediates oncogene-induced senescence, and identified posttranslational modifications that regulate the enzymatic activity and biological functions of Tip60 and PRAK.