Asymmetric impact of technological innovation, foreign direct investment and agricultural production on environmental degradation: evidence from Pakistan.

The present study analyzes the asymmetric effects of technical innovation, foreign direct investment, and agriculture productivity on Pakistan's environmental degradation from 1990 to 2020. A non-linear autoregressive model (NARDL) has been used for the analysis. The asymmetric effects have been computed for both the long and short run. The empirical results show that there is equilibrium long-run relationship among the variables. Moreover, it is found that the effect of FDI on CO2 emission is positive regardless of whether there are positive or negative shocks to FDI in the long run. The short-run results are similar except for the positive shocks to FDIat lag one, which reduces environmental degradation in Pakistan. However, in the long run, population growth and positive (negative) shocks to technical innovation have a negative and significant impact on CO2, whereas agriculture productivity is the main source of environmental degradation in Pakistan. The asymmetric tests show that FDI and agriculture productivity have strong asymmetric effects on the CO2 emissions in the long run, whereas there is weak evidence of, in the short and long run, asymmetric effects of technical innovations in Pakistan. These results are statistically significant, valid, and stable as per most of the diagnostic tests conducted and reported in the study.

The impact of economic growth, tourism, natural resources, technological innovation on carbon dioxide emission: evidence from BRICS countries.

The main objective of this manuscript was to investigate the relationships among economic development, tourism, the use of natural resources, technical advancement, and carbon dioxide emissions in the BRICS group of nations. Data from the panel was gathered from 1995 to 2018. Modern methodology tools including the CS-ARDL tests, Westerlund cointegration tests, and panel data unit root tests have been used in this study. Results of the models show that all the variables were transformed to the first difference to make it stationary. The Westerlund model test results suggest that dependent and independent variables have robust cointegration. Results of the CS-ARDL models reveal that all the variables signed, and significance are aligned with the economic theory. It indicates that except for tourism, the rest of the variables like technical innovation, natural resources, and economic growth have positive and significant effects on carbon dioxide emissions both in the short and long runs. Additionally, a 1% rise in economic growth, technical innovation, and natural resources over the long term would raise carbon dioxide emissions in the BRICS economies by 1.79%, 0.15%, and 0.10%, respectively. However, a 1% increase in tourism would result in a 0.39% decrease in carbon dioxide emissions among the nations in the panel data set. Therefore, the promotion of sustainable tourism and advancement in technological innovation is highly important in these countries, so the high impact of environmental degradation pressure may reduce to some extent. An in-addition comprehensive set of policies should be made on encouraging low-carbon transportation, promoting sustainable tourism certification, boosting local produce, reducing waste management, and provide education and awareness campaigns to tourists.

An analysis of machine learning risk factors and risk parity portfolio optimization.

Many academics and experts focus on portfolio optimization and risk budgeting as a topic of study. Streamlining a portfolio using machine learning methods and elements is examined, as well as a strategy for portfolio expansion that relies on the decay of a portfolio's risk into risk factor commitments. There is a more vulnerable relationship between commonly used trademarked portfolios and neural organizations based on variables than famous dimensionality decrease strategies, as we have found. Machine learning methods also generate covariance and portfolio weight structures that are more difficult to assess. The least change portfolios outperform simpler benchmarks in minimizing risk. During periods of high instability, risk-adjusted returns are present, and these effects are amplified for investors with greater sensitivity to chance changes in returns R.

Does Globalization Cause Greenhouse Gas Emissions in Pakistan? A Promise to Enlighten the Value of Environmental Quality.

Global environmental issues such as environmental degradation, climate change, and global warming have posed a threat to the global economy, including Pakistan. The primary source of these problems is greenhouse gas emissions. These emissions are the result of human activity. The objective of the study was to investigate the symmetric and asymmetric relationship between globalization and greenhouse gas emissions in Pakistan. The ARDL modern econometric techniques of the time series model were used. Firstly, the stationarity test favors the use of the ARDL model in this study. The BDS test result confirmed that the ARDL model has a non-linearity issue. As a result, the ARDL approach was used to test both the symmetric and asymmetric effect. The results of the asymmetric ARDL model are more robust and reliable than those of the symmetric ARDL model. According to the results of the symmetric ARDL, economic, social, and political globalization have a positive relationship with greenhouse gas emissions in both the short and long run. Furthermore, the long-run results of the asymmetric ARDL model show that positive and negative shocks of economic and political globalization have positive and negative shock effects on greenhouse gas emissions. In the long run, however, the positive shock of social globalization has a negative relationship with greenhouse gas emissions. According to the results of impulse response functions, economic globalization has a significantly more relationship with greenhouse gas emissions than social and political globalization. A policy should be developed that allows only the positive effects of globalization while prohibiting the negative effects of globalization.

Efficacy of feed improvement in livestock farming to offset climate variations in Punjab, Pakistan: silage as an example.

Globally, climate change is an alarming threat to the livestock industry. Such changes in the climate can also adversely affect the returns of livestock farmers in Pakistan. Improvement in the production process could decrease the risk of losses. This study analyzes the efficacy of silage to abate the losses in livestock profitability resulting from the climate change. The study employed cross-sectional survey data of 492 livestock farmers collected from six districts of Punjab Province, Pakistan. The data are analyzed with endogenous switching regression, considering the possibility of selection bias and endogeneity in adopting silage as a climate change adaptation measure. The study findings show a significant difference in material well-being between silage users and conventional feed users. Furthermore, training programs such as silage training and livestock development programs could be meaningful provisions to abate climate change and improve food security. It is suggested that training and development programs should be incorporated in policy plans to improve the well-being of farmers in terms of their farm revenues.

[Research on Immunomodulatory Effects of Listeria monocytogenes L-form on Mouse Splenic Dendritic Cells].

OBJECTIVE: To study the effect of Listeria monocytogenes (LM) infection on dendritic cell (DC) immune function, and to compare the difference of immune activation ability on DC cell between bacterial form (WT) and L-form. METHODS: C57BL/6 mice were randomly divided into 3 groups and infected intravenously with LM WT, LM L-form or PBS respectively. The ultrastructural characteristics of splenic DC were observed by transmission electron microscopy (TEM). The number of splenic DC, the expression of costimulatory molecules, the secretion of cytokine and the activation of splenic T lymphocyte were detected by flow cytometry. RESULTS: TEM observation found that there were a large number of filamentous pseudopodia on the surface of splenic DC cells. The cytoplasm of DC was homogeneous and its nucleus was large. After phagocytosis of bacteria, the number of pseudopodia on the surface decreased and vacuoles in the cytoplasm increased. The number of splenic DC did not show significant changes at 1 d post infection (P>0.05). However, the expression of mature phenotypic molecules were significantly up-regulated (P < 0.05), in L-form infection group, both CD80 and CD86 molecules expressed on DC surface were higher than WT group (P < 0.05). Compared with control group, the proportion of TNF-α+DC were elevated after LM infection, and the average percentage of TNF-α+DC of L-form infection group was significantly higher than that of WT group (P < 0.05). At 7 d after infection, the average percentage of CD69+ T cells of L-form group was significantly higher than that of WT group (P < 0.05). CONCLUSION: LM L-form can induce relatively high levels of TNF-α and promote DC maturation so that to enhance their antigen presenting ability.

Frailty phenotypes and mortality after lung transplantation: A prospective cohort study.

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score-adjusted Cox models. We calculated postestimation marginalized standardized risks for 1-year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1- and 4-year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6-36.0 and aHR 3.8; 95%CI: 1.8-8.0, respectively). Each 1-point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08-1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%-21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1-13.2) but not over longer follow-up. Preoperative frailty is associated with an increased risk of death after lung transplantation.

Use of Lung Allografts From Donation After Cardiac Death Donors: A Single-Center Experience.

BACKGROUND: Lung transplantation remains the only treatment for end-stage lung disease. Availability of suitable lungs does not parallel this growing trend. Centers using donation after cardiac death (DCD) donor lungs report comparable outcomes with those from brain-dead donors. Donor assessment protocols and consistent surgical teams have been advocated when considering using the use of DCD donors. We present our experience using lungs from Maastricht category III DCD donors. METHODS: Starting 2007 to July 2016, 73 DCD donors were assessed, 44 provided suitable lungs that resulted in 46 transplants. A 2012 to October 2016 comparative cohort of 379 brain-dead donors were assessed. Recipient and donor characteristics and primary graft dysfunction (PGD) and survival were monitored. RESULTS: Seventy-three DCD (40% dry run rate) donors assessed yielded 46 transplants (23 double, 6 right, and 17 left). Comparative cohort of 379 brain-dead donors yielded 237 transplants (112 double, 43 right, and 82 left). One- and 3-year recipient survival was 91% and 78% for recipients of DCD lungs and 91% and 75% for recipients of lungs from brain-dead donors, respectively. PGD 2 and 3 in DCD recipients at 72 hours was 4 of 46 (9%) and 6 of 46 (13%), respectively. Comparatively, brain-dead donor recipient cohort at 72 hours with PGD 2 and 3 was 23 of 237 (10%) and 41 of 237 (17%), respectively. CONCLUSIONS: Our experience reaffirms the use of lungs from DCD donors as a viable source with favorable outcomes. Recipients from DCD donors showed equivalent PGD rate at 72 hours and survival compared with recipients from brain-dead donors.

Donor lung assessment using selective pulmonary vein gases.

OBJECTIVES: Standard donor lung assessment relies on imaging, challenge gases and subjective interpretation of bronchoscopic findings, palpation and visual assessment. Central gases may not accurately represent true quality of the lungs. We report our experience using selective pulmonary vein gases to corroborate the subjective judgement. METHODS: Starting, January 2012, donor lungs have been assessed by intraoperative bronchoscopy, palpation and visual judgement of lung collapse upon temporary disconnection from ventilator, central gases from the aorta and selective pulmonary vein gases. Partial pressure of oxygen (pO2) <300 mmHg on FiO2 of 1.0 was considered low. The results of the chest X-ray and last pO2 in the intensive care unit were also collected. Post-transplant primary graft dysfunction and survival were monitored. RESULTS: To date, 259 consecutive brain-dead donors have been assessed and 157 transplants performed. Last pO2 in the intensive care unit was poorly correlated with intraoperative central pO2 (Spearman's rank correlation rs = 0.29). Right inferior pulmonary vein pO2 was associated (Mann-Whitney, P < 0.001) with findings at bronchoscopy [clean: median pO2 443 mmHg (25th-75th percentile range 349-512) and purulent: 264 mmHg (178-408)]; palpation [good: 463 mmHg (401-517) and poor: 264 mmHg (158-434)] and visual assessment of lung collapse [good lung collapse: 429 mmHg (320-501) and poor lung collapse: 205 mmHg (118-348)]. Left inferior pulmonary pO2 was associated (P < 0.001) with findings at bronchoscopy [clean: 419 mmHg (371-504) and purulent: 254 mmHg (206-367)]; palpation [good: 444 mmHg (400-517) and poor 282 mmHg (211-419)] and visual assessment of lung collapse [good: 420 mmHg (349-496) and poor: 246 mmHg (129-330)]. At 72 h, pulmonary graft dysfunction 2 was in 21/157 (13%) and pulmonary graft dysfunction 3 in 17/157 (11%). Ninety-day and 1-year mortalities were 6/157 (4%) and 13/157 (8%), respectively. CONCLUSIONS: Selective pulmonary vein gases provide corroborative objective support to the findings at bronchoscopy, palpation and visual assessment. Central gases do not always reflect true function of the lungs, having high false-positive rate towards the individual lower lobe gas exchange. Objective measures of donor lung function may optimize donor surgeon assessment, allowing for low pulmonary graft dysfunction rates and low 90-day and 1-year mortality.

Donors with a prior history of cardiac surgery are a viable source of lung allografts.

OBJECTIVES: End-stage lung disease continues to rise despite the lack of suitable lung donors, limiting the numbers of lung transplants performed each year. Expanded donor criteria, use of donation after cardiac death donors and the advent of ex vivo lung perfusion have resulted only in a slight increase in donor lung utilization. Organ donors with prior cardiac surgery (DPCS) present risks and technical challenges; however, they may be a potential source of suitable lung allografts with an experienced procurement surgeon. We present our experience having evaluated potential lung donors with a prior history of cardiac surgery, resulting in successful transplant outcomes. METHODS: This is a single-institution retrospective review of brain-dead organ donors that were evaluated for lung donation in the period 2012-15. Donor and recipient characteristics were collected. Post-lung transplant survival was recorded. RESULTS: From 2012 to 2015, 259 donors were evaluated, 12 with a prior history of cardiac surgery of which 4 had coronary artery bypass, 3 had aortic root replacement, 2 had aortic valve replacement, 1 pulmonary embolectomy, 1 two-time reoperative valve replacement and 1 paediatric congenital ventricular septal defect repair. DPCS, 6/12 (50% dry run) provided suitable allografts generating six single-lung transplants (three right and three left, 1 donor provided twin single-lung transplants) and one double-lung transplant. Interval between cardiac surgery and procurement for those rejected was median 5840 (IQR 2350-8640) days and interval for the donors that provided allografts was median 438 (IQR 336-1095) days (Mann-Whitney, P = 0.07). Recipient 1-year survival from DPCS is 100%. Recipient 1-year survival was 92% in allografts explanted from donors with no prior cardiac surgery (2012-13). CONCLUSION: To date, this is the largest single-centre experience using lung allografts from brain-dead DPCS. Our experience shows despite predicted technical difficulties, with good communication between thoracic and abdominal teams, successful transplant outcomes are possible, when surgeons with experience in reoperative cases are sent for lung procurements.

Short Stature and Access to Lung Transplantation in the United States. A Cohort Study.

RATIONALE: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates. OBJECTIVES: To examine the relationship between lung transplant candidate height and waiting list outcomes. METHODS: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year. MEASUREMENTS AND MAIN RESULTS: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation. CONCLUSIONS: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.

Unusual Case of Coexisting Renal Malignancies: Mucinous Tubular and Spindle Cell Carcinoma Kidney With Sarcomatoid Dedifferentiation.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a recent entity introduced in the World Health Organization 2004 Classification. It is a tumour of low malignant potential. MTSCC is a subtype of renal cell carcinoma (RCC), which is characterized by a polymorphous histology, wherein the spindled epithelial cell is an inherent carcinomatous component. We report the case of a 57-year-old man presenting with loin pain and dragging sensation. Imaging revealed a large mass arising from the left kidney. Radical nephrectomy was performed, and histopathology revealed spindle cell elements of MTSCC with low-grade cytology, which occasionally blended with tubular structures in variable mucinous stroma admixed with spindle sarcomatoid cells with marked nuclear pleomorphism, associated with significant necrosis and mitoses of up to 5/10 high-power field. A final diagnosis of MTSCC along with high-grade areas consistent with sarcomatoid dedifferentiation was made. Sarcomatoid dedifferentiation has been well documented in various subtypes of RCC, and its presence signifies a worse prognosis in RCC.

Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation.

RATIONALE: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. OBJECTIVES: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. METHODS: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. MEASUREMENTS AND MAIN RESULTS: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB. CONCLUSIONS: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

MSC therapy attenuates obliterative bronchiolitis after murine bone marrow transplant.

RATIONALE: Obliterative bronchiolitis (OB) is a significant cause of morbidity and mortality after lung transplant and hematopoietic cell transplant. Mesenchymal stromal cells (MSCs) have been shown to possess immunomodulatory properties in chronic inflammatory disease. OBJECTIVE: Administration of MSCs was evaluated for the ability to ameliorate OB in mice using our established allogeneic bone marrow transplant (BMT) model. METHODS: Mice were lethally conditioned and received allogeneic bone marrow without (BM) or with spleen cells (BMS), as a source of OB-causing T-cells. Cell therapy was started at 2 weeks post-transplant, or delayed to 4 weeks when mice developed airway injury, defined as increased airway resistance measured by pulmonary function test (PFT). BM-derived MSC or control cells [mouse pulmonary vein endothelial cells (PVECs) or lung fibroblasts (LFs)] were administered. Route of administration [intratracheally (IT) and IV] and frequency (every 1, 2 or 3 weeks) were compared. Mice were evaluated at 3 months post-BMT. MEASUREMENTS AND MAIN RESULTS: No ectopic tissue formation was identified in any mice. When compared to BMS mice receiving control cells or no cells, those receiving MSCs showed improved resistance, compliance and inspiratory capacity. Interim PFT analysis showed no difference in route of administration. Improvements in PFTs were found regardless of dose frequency; but once per week worked best even when administration began late. Mice given MSC also had decreased peribronchiolar inflammation, lower levels of hydroxyproline (collagen) and higher frequencies of macrophages staining for the alternatively activated macrophage (AAM) marker CD206. CONCLUSIONS: These results warrant study of MSCs as a potential management option for OB in lung transplant and BMT recipients.

Immunosuppression in lung transplantation.

Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

Calpain 1 knockdown improves tissue sparing and functional outcomes after spinal cord injury in rats.

To evaluate the hypothesis that calpain 1 knockdown would reduce pathological damage and functional deficits after spinal cord injury (SCI), we developed lentiviral vectors encoding calpain 1 shRNA and eGFP as a reporter (LV-CAPN1 shRNA). The ability of LV-CAPN1 shRNA to knockdown calpain 1 was confirmed in rat NRK cells using Northern and Western blot analysis. To investigate the effects on spinal cord injury, LV-CAPN1shRNA or LV-mismatch control shRNA (LV-control shRNA) were administered by convection enhanced diffusion at spinal cord level T10 in Long-Evans female rats (200-250 g) 1 week before contusion SCI, 180 kdyn force, or sham surgery at the same thoracic level. Intraspinal administration of the lentiviral particles resulted in transgene expression, visualized by eGFP, in spinal tissue at 2 weeks after infection. Calpain 1 protein levels were reduced by 54% at T10 2 weeks after shRNA-mediated knockdown (p<0.05, compared with the LV-control group, n=3 per group) while calpain 2 levels were unchanged. Intraspinal administration of LV-CAPN1shRNA 1 week before contusion SCI resulted in a significant improvement in locomotor function over 6 weeks postinjury, compared with LV-control administration (p<0.05, n=10 per group). Histological analysis of spinal cord sections indicated that pre-injury intraspinal administration of LV-CAPN1shRNA significantly reduced spinal lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing (p<0.05, n=10 per group). Together, results support the hypothesis that calpain 1 activation contributes to the tissue damage and impaired locomotor function after SCI, and that calpain1 represents a potential therapeutic target.

Horizontal ladder task-specific re-training in adult rats with contusive thoracic spinal cord injury.

PURPOSE: Using the horizontal ladder task, we examined some issues that need to be resolved before task-specific rehabilitative training can be employed clinically for the frequent contusive spinal cord injury (SCI). We hypothesized that improving recovery in task performance after contusive thoracic SCI requires frequent re-training and initiating the re-training early during spontaneous recovery. METHODS: Contusive SCI was produced at the adult female Sprague Dawley rat T10 vertebra. Task re-training was initiated one week later when occasional weight-supported plantar steps were taken overground (n = 8). It consisted of 2 repetitions each day, 5 days each week, for 3 weeks. Task performance and overground locomotion were assessed weekly. Neurotransmission through the SCI ventrolateral funiculus was examined. SCI morphometry was determined. RESULTS: Re-training did not improve task performance recovery compared to untrained Controls (n = 7). Untrained overground locomotion and neurotransmission through the SCI did not change. Lesion area at the injury epicenter as a percentage of the total spinal cord area as well as total tissue, lesion, and spared tissue, white matter, or gray matter volumes did not differ. CONCLUSIONS: For the horizontal ladder task after contusive thoracic SCI, earlier re-training sessions with more repetitions and critical neural circuitry may be necessary to engender a rehabilitation effect.

Involvement of ERK2 in traumatic spinal cord injury.

Activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) are implicated in the pathophysiology of spinal cord injury (SCI). However, the specific functions of individual ERK isoforms in neurodegeneration are largely unknown. We investigated the hypothesis that ERK2 activation may contribute to pathological and functional deficits following SCI and that ERK2 knockdown using RNA interference may provide a novel therapeutic strategy for SCI. Lentiviral ERK2 shRNA and siRNA were utilized to knockdown ERK2 expression in the spinal cord following SCI. Pre-injury intrathecal administration of ERK2 siRNA significantly reduced excitotoxic injury-induced activation of ERK2 (p < 0.001) and caspase 3 (p < 0.01) in spinal cord. Intraspinal administration of lentiviral ERK2 shRNA significantly reduced ERK2 expression in the spinal cord (p < 0.05), but did not alter ERK1 expression. Administration of the lentiviral ERK2 shRNA vector 1 week prior to severe spinal cord contusion injury resulted in a significant improvement in locomotor function (p < 0.05), total tissue sparing (p < 0.05), white matter sparing (p < 0.05), and gray matter sparing (p < 0.05) 6 weeks following severe contusive SCI. Our results suggest that ERK2 signaling is a novel target associated with the deleterious consequences of spinal injury.

Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.

BACKGROUND: Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients. METHODS: We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections. RESULTS: The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81). CONCLUSIONS: Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.

Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin.

Human metapneumovirus (hMPV) has recently been shown to be a prominent cause of respiratory infections in immunocompromised hosts, and is associated with high morbidity and mortality. We report a case of hMPV pneumonia in a lung transplant recipient presenting with respiratory failure and sepsis syndrome. hMPV was diagnosed by polymerase chain reaction, and treated with intravenous ribavirin with a successful outcome.