Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes

Abstract Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.

A novel treatment for skin repair using a combination of spironolactone and vitamin D3.

Injury of the skin from exposure to toxic chemicals leads to the release of inflammatory mediators and the recruitment of immune cells. Nitrogen mustard (NM) and other alkylating agents cause severe cutaneous damage for which there are limited treatment options. Here, we show that combined treatment of vitamin D3 (VD3) and spironolactone (SP), a mineralocorticoid receptor antagonist, significantly improves the resolution of inflammation and accelerates wound healing after NM exposure. SP enhanced the inhibitory effect of VD3 on nuclear factor-kB activity. Combined treatment of NM-exposed mice with VD3 and SP synergistically inhibited the expression of iNOS in the skin and decreased the expression of matrix metallopeptidase-9, C-C motif chemokine ligand 2, interleukin (IL)-1α, and IL-1ß. The combined treatment decreased the number of local proinflammatory M1 macrophages resulting in an increase in the M2/M1 ratio in the wound microenvironment. Apoptosis was also decreased in the skin after combined treatment. Together, this creates a proresolution state, resulting in more rapid wound closure. Combined VD3 and SP treatment is effective in modulating the immune response and activating anti-inflammatory pathways in macrophages to facilitate tissue repair. Altogether, these data demonstrate that VD3 and SP may constitute an effective treatment regimen to improve wound healing after NM or other skin chemical injury.

Evaluation of Complications in Postpartum Women Receiving Therapeutic Anticoagulation.

OBJECTIVE: To evaluate complications associated with early postpartum therapeutic anticoagulation. METHODS: A multicenter retrospective cohort study was done to evaluate the association between therapeutic anticoagulation postpartum and major complications (hemorrhagic and wound complications). Secondary outcomes included minor complications, risk factors associated with total complications (including the time to therapeutic anticoagulation resumption after delivery) and recurrent thrombotic events within 6 weeks postpartum. RESULTS: From 2003 to 2015, 232 consecutive women were treated with therapeutic anticoagulation within 96 hours postpartum; among those treated, 91 received unfractionated heparin, 138 received low-molecular-weight heparin, and three received other anticoagulants. The primary outcome, a composite of major hemorrhagic complications (requiring transfusion, hospitalization, volume resuscitation, transfer to intensive care unit, or surgery) and major wound complications, occurred in 7 of 83 (8.4%) for cesarean deliveries and 9 of 149 (6.0%) for vaginal deliveries (P=.490). Total complications (including major and minor hemorrhagic and wound complications) occurred in 13 of 83 (15.7%) for cesarean deliveries compared with 9 of 149 (6.0%) for vaginal deliveries (P=.016). When comparing cases associated with and without complications, the median delay before resuming anticoagulation was significantly shorter for both cesarean (12 vs 33 hours, P=.033) and vaginal deliveries (6 vs 19 hours, P=.006). For vaginal deliveries, 8 of 51 (15.7%) women had complications when anticoagulation was started before 9.25 hours postpartum, compared with 1 of 98 (1.0%) when started after 9.25 hours. For cesarean deliveries, 7 of 21 (33.3%) of women experienced complications compared with 6 of 62 (9.7%) if anticoagulation was started before or after 15.1 hours, respectively. Two (0.9%) episodes of venous thromboembolism occurred within 6 weeks postpartum. CONCLUSION: Among postpartum women who received early therapeutic anticoagulation, major complications occurred in 8.4% for cesarean deliveries and 6.0% for vaginal deliveries. Complications were associated with earlier resumption of therapeutic anticoagulation, particularly before 9.25 hours for vaginal deliveries and before 15.1 hours for cesarean deliveries.

Luteolin protects against testicular injury induced by lead acetate by activating the Nrf2/HO-1 pathway.

Lead (Pb) is a toxic heavy metal that is harmful to humans, especially male reproductive organs. Luteolin (LUT) is a naturally occurring flavonoid with numerous biological activities. Our aim was to investigate the possible reproprotective effect of LUT against testicular deficits induced by Pb intoxication. In the present study, 28 rats were distributed into 4 groups: control, LUT (50 mg/kg), lead acetate (PbAc, 20 mg/kg), and LUT + PbAc groups, in which rats were pre-treated with LUT 3 hr before PbAc injection. All animals were treated for 7 days. Oxidative stress, inflammatory and apoptotic markers along with histopathological changes have been examined using spectrophotometric, ELISA, real-time PCR, and histopathological methods. PbAc injection elevated Pb concentration in testicular tissue and decreased levels of sex hormones. PbAc intoxication exacerbated lipoperoxidation and nitric oxide formation, depleted superoxide dismutase, and catalase activities along with glutathione and its originated enzymes (glutathione peroxidase and glutathione reductase). At the molecular level, PbAc deactivated nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in the testicular tissue. In addition, PbAc toxicity induced inflammatory and apoptotic cascades in testicular tissue as evidenced by the increased tumor necrosis factor-alpha, interleukin-1 beta, inducible nitric oxide synthase, Bax, and caspase 3, while Bcl-2 was declined. Histopathological examination of testicular tissue also revealed that PbAc caused degeneration alterations in spermatogenic cells, the spermatogenic epithelial cells were disconnected from the basement membrane, and the seminiferous tubules were vacuolated. Remarkably, pre-treatment with LUT minimized significantly the testicular damage induced by PbAc. Therefore, we conclude that LUT may have a beneficial effect against PbAc-induced testicular injury through preventing oxidative challenge, inflammation, and finally apoptosis.

Association of eszopiclone, zaleplon, or zolpidem with complex sleep behaviors resulting in serious injuries, including death.

PURPOSE: To identify and analyze postmarketing cases of complex sleep behaviors (CSBs) resulting in serious injuries, including death, associated with eszopiclone, zaleplon, or zolpidem (Z-drugs). METHODS: Retrospective analysis of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 16 December 1992 through 27 February 2018 and medical literature using PubMed and EMBASE. We used random sampling and descriptive statistics. RESULTS: We identified 66 cases that met inclusion and exclusion criteria, four of which were identified in the medical literature. Twenty cases reported death and 46 cases reported serious injuries in association with CSBs occurring after the use of a Z-drug. Fatal cases described events, such as carbon monoxide poisoning, drowning, falls, hypothermia, motor vehicle collisions, and apparent completed suicide. Nonfatal cases resulting in serious injuries described events, such as accidental overdoses, falls, gunshot wounds, hypothermia, third-degree burns, and self-injuries or suicide attempts. Twenty-two cases reported a previous episode of a CSB while taking a Z-drug prior to the event reported in this case series. CONCLUSIONS: The FAERS and medical literature cases support the need for increased awareness of the consequences that may occur because of CSBs associated with the use of Z-drugs. Therefore, to protect public health, regulatory actions were taken, including adding a Boxed Warning, a Contraindication in patients who have experienced a prior episode of a CSB with a Z-drug, and updating the existing Warnings and Precautions. An FDA Drug Safety Communication was also disseminated to alert healthcare professionals and the public of this potential risk.

Injuries and poisonings associated with methamphetamine use: sentinel surveillance, the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP), 2011-2019. / Blessures et intoxications associées à la consommation de méthamphétamine : surveillance sentinelle à l'aide de la plateforme électronique du Système canadien hospitalierd'information et de recherche en prévention des traumatismes (eSCHIRPT), 2011 à 2019.

Information from emergency department (ED) visits for methamphetamine-related injuries and poisonings between 1 April 2011 and 9 August 2019 were captured from 19 sentinel sites across Canada for all ages. Overall, 1093 cases (97.6/100 000 eCHIRPP cases) were identified (59.4% male), with female patients experiencing more poisonings (71% vs 57.4% for males). Unintentional injuries and poisoning accounted for 14.8% of ED presentations. Self-harm (while or as a result of consuming methamphetamine) accounted for 11.4% of cases. The circumstances surrounding injuries and poisonings associated with methamphetamine are varied and include self-harm, fall-related brain injuries, mental illness, criminal activity and other circumstances. These domains should be taken into account when developing mitigation strategies.

1093 methamphetamine-related injury and poisoning cases presented to participating emergency departments (EDs). 71.4% of patients aged 10­14 years were female; of those aged 15­19 years, 63.7% were female. 70.4% of the patients aged 20 years plus were male. Of the 689 cases that also involved other substances (63%), 40.9% involved two or more other substances. Alcohol (24.4%), cannabis (10.7%), cocaine (7.7%), heroin (5.4%), opiates (3.6%) and other substances (7.3%) were involved when only one substance other than methamphetamine was used. Compared to males, females had more poisonings, while males more frequently had multiple injuries. Self-harm accounted for 11.4% of cases.

Les services des urgences participants ont traité 1093 cas de blessures et de lésions liées à la méthamphétamine. La proportion de cas concernant les filles était de 71,4 % chez les 10 à 14 ans et de 63,7 % chez les 15 à 19 ans. Chez les patients de 20 ans et plus,70,4 % étaient des hommes. Des 689 cas où d'autres substances étaient en cause (63 %), 40,9 % impliquaient deux substances ou plus. Dans les cas où une seule substance autre que la méthamphétamine était en cause, celle­ci était l'alcool (24,4 %), le cannabis (10,7 %), la cocaïne (7,7 %), l'hé­ roïne (5,4 %), un opiacé (3,6 %) ou une autre substance (7,3 %). La proportion d'intoxications était plus élevée chez les femmes, tandis que les blessures multiples étaient plus fréquentes chez les hommes. Des blessures auto­infligées ont été commises dans 11,4 % des cas.

National Toxic Substances Incidents Program - Nine States, 2010-2014.

PROBLEM/CONDITION: Every year in the United States, thousands of toxic substance incidents harm workers, first responders, and the public with the potential for catastrophic consequences. Surveillance data enable public health and safety professionals to understand the patterns and causes of these incidents, which can improve prevention efforts and preparation for future incidents. PERIOD COVERED: 2010-2014. DESCRIPTION OF SYSTEM: In 2010, the Agency for Toxic Substances and Disease Registry (ATSDR) initiated the National Toxic Substance Incidents Program (NTSIP), and it was retired in 2014. Nine state health departments participated in NTSIP surveillance: California, Louisiana, North Carolina, New York, Missouri, Oregon, Tennessee, Utah, and Wisconsin. The states conducted surveillance on acute toxic substance incidents, defined as an uncontrolled or illegal acute (lasting <72 hours) release of any toxic substance including chemical, biologic, radiologic, and medical materials. Surveillance focused on associated morbidity and mortality and public health actions. This report presents an overview of NTSIP and summarizes incidents and injuries from the nine participating states during 2010-2014. RESULTS: During 2010-2014, participating state health departments reported 22,342 incidents, of which 13,529 (60.6%) met the case definition for acute toxic substance incidents, and included 6,635 injuries among 5,134 injured persons, of whom 190 died. A trend analysis of the three states participating the entire time showed a decrease in the number of incidents with injuries. NTSIP incidents were 1.8 times more likely and injured persons were 10 times more likely to be associated with fixed facilities than transportation. Natural gas, carbon monoxide, ammonia, and chemicals used in illegal methamphetamine production were the most frequent substances in fixed-facility incidents. Sodium and potassium hydroxide, hydrochloric acid, natural gas, and sulfuric acid were the most frequent substances in transportation-related incidents. Carbon monoxide was the most frequent substance in incidents with a large number of injured persons, and chemicals used in illegal methamphetamine production were the most frequent substance in incidents involving decontamination. Incidents most frequently occurred during normal business days (Monday through Friday) and hours (6:00 a.m.-5:59 p.m.) and warmer months (March-August). The transportation and warehousing industry sector had the largest number of incidents (4,476); however, most injured persons were injured in their private residences (1,141) or in the industry sectors of manufacturing (668), educational services (606), and real estate rental and leasing (425). The most frequently injured persons were members of the public (43.6%), including students. Injured first responders, particularly police, frequently were not wearing any chemically protective equipment. Respiratory system problems (23.9%) were the most frequently reported symptoms among injured persons and, in a related finding, volatilization was the most frequent type of release in incidents with injured persons. INTERPRETATION: Industrial and transportation incidents occur frequently and have the potential for catastrophic outcomes. However, exposures to toxic substances occur frequently in other settings. Carbon monoxide, natural gas, and chemicals used in illegal methamphetamine production are commonly found in places where persons live, work, attend school, and recreate and are large contributors to incidents affecting the public. Having active NTSIP state surveillance programs did appear to improve the incidents with morbidity and/or mortality, but these programs have ended. PUBLIC HEALTH ACTION: Archived NTSIP public use data are available to download from the website for analysis. There are also many publications and reports on the website to help understand chemical risks. In addition, jurisdictions might choose to collect surveillance data themselves in a similar manner to what NTSIP states did. Chemical incident surveillance data can be used by public health and safety practitioners, worker representatives, emergency planners, preparedness coordinators, industries, and emergency responders to prepare for and prevent chemical incidents and injuries. As noted by the U.S. Chemical Safety Board, more action needs to be taken to prevent large industrial incidents. Although preventing such incidents might not be in the realm of public health, describing the public health implications and preparing for them is. Another important finding of NTSIP is that industrial incidents are only part of the problem. For example, a large number of persons were injured in a private residence or vehicle (22.2%) and an educational facility (11.8%). Public health professionals must resourcefully target prevention and preparedness to protect vulnerable populations in locations where they might spend time (e.g., schools, daycares, nursing homes, recreational areas, jails, prisons, and hospitals). Reducing the threat of chemical incidents and injuries in the United States will require a concerted effort with a variety of stakeholders including industry and labor, responder groups, policymakers, academia, and citizen advocacy groups.

Anhydrous Ammonia Chemical Release - Lake County, Illinois, April 2019.

On April 25, 2019, a farm tractor towing two 2-ton ammonia tanks on a county road in Lake County, Illinois, experienced a mechanical failure that resulted in the release of anhydrous ammonia, a colorless, pungent, irritating gas that can cause severe respiratory and ocular damage (1). Approximately 80% of anhydrous ammonia produced in the United States is used as a fertilizer in agriculture (1). Eighty-three persons, including first responders, motorists, and neighborhood residents, were evaluated at area hospitals because of exposure to the gas. Two weeks after the release, the Agency for Toxic Substances and Disease Registry (ATSDR) and CDC's National Center for Environmental Health (NCEH) collaborated with the Lake County Health Department and the Illinois Department of Public Health on an investigation using ATSDR's Assessment of Chemical Exposures program to describe the release, review the emergency response, and determine health effects associated with the exposure. First responders, community residents, and hospital personnel reported communication challenges related to the nature of the gas release and effective protective measures. Among the 83 persons evaluated at six area hospitals for effects of the chemical release, 14 (17%) were hospitalized, including eight (10%) who were admitted to the intensive care unit (ICU), seven (8%) of whom required endotracheal intubation and mechanical ventilation; no deaths occurred. In addition, ICU health care providers experienced symptoms of secondary exposure. The National Institute for Occupational Safety and Health's Emergency Responder Health Monitoring and Surveillance Program has specific recommendations and tools to protect responders during all phases of a response (2). Hospitals also need to review institutional policies and procedures for chemical mass casualty events, including decontamination (3). Prompt and correct identification of hazardous material (hazmat) events, and clear communication among responding entities, including on-scene and hospital responders, is important to ensure effective response after a chemical release.

Is Opioid Prescribing Driving Trauma Recidivism or Is Trauma Driving Opioid Use?

In the past 30 years, opioid prescription rates have quadrupled and hospital admissions for overdose are rising. Previous studies have focused on alcohol use and trauma recidivism, however rarely evaluating recidivism and opioid use. We hypothesized there is an association between opioid use and trauma recidivism. This is a retrospective review of patients with multiple admissions for traumatic injury. Demographics, opioid toxicology screen (TS) results, and injury characteristics were collected. Statistical analysis was performed with chi-squared and Poisson regression models. One thousand six hundred forty-nine patients (age ≥18 years) had multiple trauma admissions. Seven hundred nine patients had TS data for both admissions. Thirty-one per cent (218) were TS positive on the 1st admission compared with 34 per cent (244) on their 2nd admission. Fifty-five per cent of patients who were TS positive on the 1st admission were positive on their 2nd admission, whereas 25 per cent who were TS negative on the 1st admission were subsequently positive on their 2nd admission (P < 0.0001). Patients who were TS positive on the subsequent admission were less severely injured than TS negative patients (Injury Severity Score > 15, 26.3% vs 22.3%, P = 0.04). The only significant risk factor for being TS positive on the 2nd admission was being TS positive on the 1st admission (relative risk = 2.18, P < 0.001). A previous history of opioid use is the strongest predictor of recurrent use in recidivists.

Sulfur Mustard Exposure: Review of Acute, Subacute, and Long-Term Effects and Their Management.

Sulfur mustard has been used in conflicts for more than a century. Despite international recognized bans on the use of chemical weapons, there continue to be reports of their use. The authors provide a contemporary overview of sulfur mustard injury and its management in the acute, subacute, and chronic periods.

Pool Chemical Injuries in Public and Residential Settings - United States, 2008-2017, and New York, 2018.

Pool chemicals are added to water in treated recreational water venues (e.g., pools, hot tubs/spas, and water playgrounds) primarily to protect public health. Pool chemicals inactivate pathogens (e.g., chlorine or bromine), optimize pH (e.g., muriatic acid), and increase water clarity, which helps prevent drowning by enabling detection of distressed swimmers underwater. However, pool chemicals can cause injuries if mishandled. To estimate the annual number of U.S. emergency department (ED) visits for pool chemical injuries, CDC analyzed 2008-2017 data from the National Electronic Injury Surveillance System (NEISS), operated by the U.S. Consumer Product Safety Commission (CPSC). During 2015-2017, pool chemical injuries led to an estimated 13,508 (95% confidence interval [CI] = 9,087-17,929) U.S. ED visits; 36.4% (estimated 4,917 [95% CI = 3,022-6,811]) of patients were aged <18 years. At least 56.3% (estimated 7,601 [95% CI = 4,587-10,615]) of injuries occurred at a residence. Two thirds of the injuries occurred during the period from Memorial Day weekend through Labor Day. This report also describes a toxic chlorine gas incident that occurred at a public pool in New York in 2018. Pool chemical injuries are preventable. CDC's Model Aquatic Health Code (MAHC) is an important resource that operators of public treated recreational water venues (e.g., at hotels, apartment complexes, and waterparks) can use to prevent pool chemical injuries.

Opioid dependency is independently associated with inferior clinical outcomes after trauma.

INTRODUCTION: Increased use of opioids has led to higher rates of overdose and hospital admissions. Studies in trauma populations have focused on outcomes associated with acute intoxications rather than addiction. We hypothesize that clinical outcomes after injury would be inferior for opioid-dependent patients compared to opioid-naïve patients. METHODS: We identified all opioid-dependent adult patients admitted to an academic level I trauma center in 2016 with an Injury Severity Score (ISS) ≥ 5. Patients were further categorized by their pattern of opioid dependency into prescription abuse, illicit abuse, or chronic pain subgroups. Outcome measures included length of stay (LOS), major complications, mortality, non-home discharge, ventilator days, and readmissions. Regression models were adjusted for patient demographics, insurance, ISS, and comorbidities. RESULTS: Of the 1450 patients who met the inclusion criteria, 18% were opioid-dependent. Among opioid-dependent patients, 30%, 27%, and 43% were prescription abuse, illicit abuse, and chronic pain patients, respectively. Compared to opioid-naïve (non-users) patients, opioid-dependent patients had longer LOS, more ventilator days, more non-home discharges, and higher readmission rates. Subgroup analysis revealed significant differences among all cohorts when compared to non-users in LOS, non-home discharge, readmissions, and major complications. Opioid dependency was not associated with mortality. CONCLUSION: Opioid dependency was detected in 18% of trauma patients and was independently associated with inferior outcomes. The impact of opioid dependency affects each opioid subgroup differently with all cohorts demonstrating increased 30-day readmissions. Opioid dependent patients may be targeted for risk interventions to reduce LOS, non-home discharge, complications and readmissions.

Healthcare Utilisation, Morbidities and Alcohol Use Monitoring Prior to Alcoholic Psychosis Diagnosis.

AIMS: The aim of this study was to describe healthcare utilisation, morbidities and monitoring of alcohol use in patients prior to a diagnosis of alcoholic psychosis in order to inform the early identification of patients at risk. METHODS: Using linked general practice and hospitalisation data in England (April 1997 to June 2014), we identified 1731 individuals (≥18 years) with a clinical recorded diagnosis of alcoholic psychosis and 17,310 matched controls without the disorder, we examined all prior general practitioner (family doctor) visits, hospitalisations, medically recorded morbidities and alcohol assessment/interventions records. Poisson regression models were used to compare rates of healthcare utilisation in people with alcoholic psychosis to those without. Logistic regression models were used to evaluate the association between alcoholic psychosis and prior morbidities. RESULTS: Patients with alcoholic psychosis showed increased levels of healthcare utilisation at least 5 years prior to their diagnosis. The most common reasons for prior healthcare visits were seizures and injuries and there was >4-fold higher rate of seizures, unintentional injuries and self-harm incidents among these patients up to 10 years prior to diagnosis, compared to the control population. A high proportion (78%) of patients had their alcohol consumption recorded, 50% had a record of heavy drinking but only one in five had any evidence of receiving an alcohol-related intervention. CONCLUSION: Patients present more often with seizures and injuries than the general population several years prior to a diagnosis of alcoholic psychosis. These visits represent opportunities for preventive action and imply that we may be missing opportunities to intervene.

Gender specific association between the use of complementary and alternative medicine (CAM) and alcohol consumption and injuries caused by drinking in the sixth Tromsø study.

BACKGROUND: Alcohol is consumed almost worldwide and is the most widely used recreational drug in the world. Harmful use of alcohol is known to cause a large disease-, social- and economic burden on society. Only a few studies have examined the relationship between CAM use and alcohol consumption. To our knowledge there has been no such research in Norway. The aim of this study is to describe and compare alcohol consumption and injuries related to alcohol across gender and different CAM approaches. METHODS: The data used in this study is based on questionnaire data gathered from the sixth Tromsø Study conducted between 2007 and 2008. Information on CAM use and alcohol consumption was available for 6819 women and 5994 men, 64.8% of the invited individuals. Pearson chi-square tests and independent sample t-tests were used to describe the basic characteristics of the participants and to calculate the differences between men and women regarding these variables. Binary logistic regression analyses were used to investigate the associations between the different CAM approaches and alcohol consumptions and injuries caused by drinking. RESULTS: Women who drank alcohol more than once a month were more likely to have applied herbal or "natural" medicine and self-treatment techniques (meditation, yoga, qi gong or tai-chi), compared to those who never drank, and those who only drank monthly or less. For women, an association was also found between having experienced injuries caused by drinking and use of self-treatment techniques and visit to a CAM practitioner. No association was found between amount of alcohol consumed and use of CAM approaches. For men, an association was found between injuries caused by drinking and use of herbal or "natural" medicine. CONCLUSION: The findings from this cross-sectional study suggests that women who drink frequently are more likely to use "natural" medicine and self-treatment techniques. Both men and women who had experienced injuries because of their drinking were more likely to have used CAM approaches.

Surveillance of carbon monoxide-related incidents - Implications for prevention of related illnesses and injuries, 2005-2014.

BACKGROUND: Carbon monoxide (CO) is an insidious gas responsible for approximately 21,000 emergency department visits, 2300 hospitalizations, and 500 deaths in the United States annually. We analyzed 10 combined years of data from two Agency for Toxic Substances and Disease Registry acute hazardous substance release surveillance programs to evaluate CO incident-related injuries. METHODS: Seventeen states participated in these programs during 2005-2014. RESULTS: In those 10years, the states identified 1795 CO incidents. Our analysis focused on 897 CO incidents having injured persons. Of the 3414 CO injured people, 61.0% were classified as general public, 27.7% were employees, 7.6% were students, and 2.2% were first responders. More than 78% of CO injured people required hospital or pre-hospital treatment and 4.3% died. The location for most injured people (39.9%) were homes or apartments, followed by educational facilities (10.0%). Educational services had a high number of people injured per incident (16.3%). The three most common sources of CO were heating, ventilation, and air conditioning systems; generators; and motor vehicles. Equipment failure was the primary contributing factor for most CO incidents. CONCLUSIONS: States have used the data to evaluate trends in CO poisoning and develop targeted public health outreach. Surveillance data are useful for setting new policies or supporting existing policy such as making CO poisoning a reportable condition at the state level and requiring CO alarms in all schools and housing. Public health needs to remain vigilant to the sources and causes of CO to help reduce this injury and death.

Icariin possesses chondroprotective efficacy in a rat model of dexamethasone-induced cartilage injury through the activation of miR-206 targeting of cathepsin K.

The present study aimed to investigate the articular cartilage and chondrocytes of dexamethasone (DXM)-induced cartilage injuries in rats in response to treatment with icariin, as well as the implicated molecular mechanism. Effects of icariin on bone metabolism and articular cartilage in experimental rats were investigated. Subsequently, the present study assessed dysregulated microRNA (miRNA) in the articular cartilage of experimental rats, and validated the significant miRNA and their targets. Finally, the effects of icariin on chondrocytes in experimental rats and the implicated molecular mechanism were explored. Quantitative polymerase chain reaction demonstrated that icariin significantly reversed DXM-induced bone degradation and stimulated bone regeneration. In addition, some notable changes in articular cartilage were also observed following continuous administration of icariin to DXM-treated rats, including enhanced cartilage area (revealed by safranin-O staining), substantial decrements in serum concentrations of deoxypyridinoline and C-terminal telopeptide of type II collagen, reduced expression of collagen type I and matrix metalloproteinase-13, as well as elevated expression of transforming growth factor-ß. Furthermore, miR-206 was determined to be significantly upregulated in the icariin group compared with the DXM-treated group. A luciferase assay further validated cathepsin K as the target RNA of miR-206. Additionally, icariin (100 µM) facilitated the viability of chondrocytes and reduced apoptotic chondrocytes. More importantly, icariin (100 µM) not only abolished the inhibition effect of DXM on miR-206 expression in chondrocytes, but also eliminated the enhancing effect of DXM on cathepsin K expression. Overall, the present study identified icariin as a novel therapeutic agent in DXM-induced cartilage injury in rats, and revealed that the activation of miR-206 targeting of cathepsin K may be responsible for the chondroprotective efficacy of icariin.

Papel dos receptores purinérgicos em modelo animal de doença de Parkinson / Role of purinergic receptors in an animal model of Parkinsons Disease

A Doença de Parkinson é uma doença altamente incapacitante e de grande prevalência. Pouco se sabe sobre sua etiologia e os tratamentos atuais consistem na diminuição dos sintomas, uma vez que ainda não foi encontrada uma maneira de reverter o déficit de neurônios dopaminérgicos observados nos pacientes acometidos. Sabe-se que os receptores purinérgicos são encontrados por todo o sistema nervoso central, não só no indivíduo adulto como também em diferentes estágios do desenvolvimento embrionário e estão envolvidos com proliferação e diferenciação celular. Este trabalho estudou a participação dos receptores purinérgicos em modelo animal de doença de Parkinson por lesão dos neurônios dopaminérgicos da via nigroestriatal com 6-OH dopamina (6-OHDA). Realizamos a análise do perfil de expressão gênica dos diferentes receptores após a lesão e subsequente modulação. Observamos expressão gênica alterada dos receptores P2X7 e P2Y6 até 5 semanas após a lesão. O uso do antagonista do receptor P2X7 Brilliant Blue G (BBG) induziu a regeneração da via nigroestriatal e o uso do antagonista do receptor P2Y6 MRS2578 preveniu a morte dos neurônios. Como esses efeitos foram acompanhados pela inativação de células microgliais, supõe-se que o controle do microambiente neuroinflamatório causado pela injeção de 6-OHDA seja a principal causa do efeito antiparkinsoniano observado pelo tratamento com BBG e MRS2578. Além disso, o transplante celular com células precursoras neuraisnão foi capaz de reverter o comportamento hemiparkinsoniano dos animais lesionados. Apesar do uso concomitante com BBG reduzir o comportamento, parece que esse efeito deve-se ao BBG per se, uma vez que o tratamento somente com o antagonista de P2X7 foi mais eficaz. De maneira geral, a modulação da atividade dos receptores purinérgicos se mostrou uma ferramenta promissora na pesquisa de cura e compreensão das bases moleculares da Doença de Parkinson

Parkinson's disease is a highly disabling and prevalent disease. Little is known about its etiology and the current treatments consist in the reduction of the symptoms, since there is no known method to reverse the dopaminergic neurons deficit observed in patients. Purinergic receptors are found throughout the central nervous system, not only in the adult individual but also at different stages of embryonic development, and are involved in proliferation and differentiation. This work investigated the role of purinergic receptors in the animal model of Parkinson's disease induced by 6-OH dopamine (6-OHDA) injection and consequent death of dopaminergic neurons of the nigrostriatal pathway. Patterns of purinergic receptors gene expression after the lesion and subsequent modulation were analyzed. We observed altered gene expression of P2X7 and P2Y6 receptors within 5 weeks of injury. The use of the P2X7 receptor antagonist Brilliant Blue G (BBG) induced the regeneration of the nigrostriatal pathway and treatment with P2Y6 receptor antagonist MRS2578 prevented the death of the neurons. Since these effects were accompanied by the inactivation of microglial cells, it is assumed that the control of neuroinflammatory milieu caused by the 6-OHDA injection is the main cause of the antiparkinsonian effect observed by the treatment with BBG and MRS2578. In addition, transplantation with neural precursor cells was not able to reverse the hemiparkinsonian behavior of injured animals. Although concomitant use with BBG improved cell engraftment, it appears that this effect is due to BBG per se, since treatment with only this P2X7receptor antagonist was more effective. In general, modulation of purinergic receptor activity showed to be a promising tool in the research of cure and understanding of the molecular bases of Parkinson's Disease

Alcohol or Drug Use and Trauma Recidivism.

BACKGROUND: Alcohol, illicit drugs, and psychotropic medications are well-known causes of traumatic events. However, the association of each type of substance with trauma recidivism remains unclear. OBJECTIVES: The purpose of this study was to quantify the strength of associations between the type of substance detected in patients admitted for traumatic injury and trauma recidivism, defined as a documented history of past trauma. METHODS: The presence of alcohol and drugs (cannabis, cocaine, amphetamines, methamphetamines, benzodiazepines, opiates, methadone, barbiturates, and tricyclic antidepressants) was analyzed in 1,156 patients between 16 and 70 years old, hospitalized in a trauma hospital between November 2011 and March 2015. Their past trauma history was retrieved from the health information system, which included patient health histories since 1999. Multinomial logistic regression analysis was used to estimate the strength of the association between types of substances detected in current trauma patients and trauma recidivism (documented history of past trauma). RESULTS: At least one substance was detected in 521 patients (45.1%): only alcohol in 159 (13.7%), only cannabis in 62 (5.4%), only psychotropic medications/opioids in 145 (12.5%), only cocaine/amphetamines in 14 (1.2%), and a combination of these groups in 141 (12.2%). The consumption of alcohol, illicit drugs, and/or psychotropic medications was associated with increased recidivism in all substance groups; the adjusted odds ratio for multiple recidivism was 3.17 (95% CI [2.29, 4.39]). CONCLUSION: Patients who screened positive for alcohol, illicit drugs, and/or psychotropic medications had a higher frequency of past trauma history compared with patients with negative tests, independently of age, gender, or the presence of previous psychiatric disorders.

Association of benzodiazepine and Z-drug use with the risk of hospitalisation for fall-related injuries among older people: a nationwide nested case-control study in Taiwan.

BACKGROUND: Non-benzodiazepine hypnotics (Z-drugs) are advocated to be safer than benzodiazepines (BZDs). This study comprehensively investigated the association of BZD and Z-drug usage with the risk of hospitalisation for fall-related injuries in older people. METHODS: This study used the Taiwan National Health Insurance Database with a nested matched case-control design. We identified 2238 elderly patients who had been hospitalised for fall-related injuries between 2003 and 2012. They were individually matched (1:4) with a comparison group by age, sex, and index year. Conditional logistic regression was used to determine independent effects of drug characteristics (type of exposure, dosage, half-life, and polypharmacy) on older people. RESULTS: Older people hospitalisation for fall-related injuries were significantly associated with current use of BZDs (adjusted odds ratio [AOR] = 1.32, 95% confidential interval [CI] = 1.17-1.50) and Z-drugs (AOR = 1.24, 95%CI = 1.05-1.48). At all dose levels of BZDs, high dose levels of Z-drugs, long-acting BZD, and short-acting BZD use were all significantly increased the risk of fall-related injuries requiring hospitalisation. Polypharmacy, the use of two or more kinds of BZDs, one kind of BZD plus Z-drugs and two or more kinds of BZDs plus Z-drugs, also significantly increased the risk (AOR = 1.61, 95% CI = 1.38-1.89; AOR = 1.65, 95% CI = 1.08-2.50, and AOR = 1.58, 95% CI = 1.21-2.07). CONCLUSIONS: Different dose levels and half-lives of BZDs, a high dose of Z-drugs, and polypharmacy with BZDs and Z-drugs were associated with an increased risk of fall-related injury requiring hospitalisation in older people. Physicians should balance the risks and benefits when prescribing these drug regimens to older people considering the risk of falls.