Short-term Injection Research Articles

Estimation of CO2 storage capacities in saline aquifers using material balance

Estimating CO2 storage capacities is crucial in developing carbon capture and storage projects. Material balance equation (MBE) methods, widely employed for oil and gas reserve estimation, offer a direct approach to estimating CO2 storage capacities. However, previous MBE methods rely on an original fluid in-place volume calculated using volumetric methods to estimate CO2 storage capacities, lacking validation for accuracy. It is essential to accurately estimate the original fluid in-place volume, representing the pore volume, as it substantially influences CO2 storage capacity. This study presents a refined MBE method that ensures accurate estimates of CO2 storage capacities by validating the original fluid in-place volumes in saline aquifers. The accuracy of this method was evaluated by comparing it with a commercial reservoir simulator for a synthetic aquifer example and the Sleipner L9 model. In the synthetic aquifer example, the relative error in CO2 storage capacity estimation with the proposed MBE method was only 2.09%, even when short-term (1-year) injection data were utilized. The proposed MBE method demonstrates consistent accuracy in estimating CO2 storage capacities under different aquifer properties, operating conditions, and MBE-related conditions. The proposed MBE method also accurately estimated the CO2 storage capacity in the Sleipner L9 model, achieving a relative error of 3.47%.

Pentylenetetrazole kindling induces dynamic changes in GAD65 expression in hippocampal somatostatin interneurons

IntroductionOne of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure. MethodsMale rats were injected with pentylenetetrazole (PTZ kindling: n = 30) or saline (control: n = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points. ResultsBimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM+) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABAAR α1, GABABR1, and VGAT cells showed no change following short- or long-term PTZ kindling. ConclusionPTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM+ cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.

Robust Short-Term Operation of AC Power Network With Injection Uncertainties

With uncertain injections from Renewable Energy Sources (RESs) and loads, deterministic AC Optimal Power Flow (OPF) often fails to provide optimal setpoints of conventional generators. A computationally time-efficient, economical, and robust solution is essential for ACOPF with short-term injection uncertainties. Usually, applying Robust Optimization (RO) for conventional non-linear ACOPF results in computationally intractable Robust Counterpart (RC), which is undesirable as ACOPF is an operational problem. Hence, this paper proposes a single-stage non-integer non-recursive RC of ACOPF, using a dual transformation, for short-term injection uncertainties. The proposed RC is convex, tractable, and provides base-point active power generations and terminal voltage magnitudes (setpoints) of conventional generators that satisfy all constraints for all realizations of defined injection uncertainties. The non-linear impact of uncertainties on other variables is inherently modeled without using any affine policy. The proposed approach also includes the budget of uncertainty constraints for low conservatism of the obtained setpoints. Monte-Carlo Simulation (MCS) based participation factored AC power flows validate the robustness of the obtained setpoints on NESTA and case9241pegase systems for different injection uncertainties. Comparison with previous approaches indicates the efficacy of the proposed approach in terms of low operational cost and computation time.

Mechanistic Study and Optimization of High Water Cut Phase Management Strategies in Fracture-Vuggy Carbonate Reservoirs with Bottom Water

Fracture-vuggy carbonate reservoirs commonly exhibit sufficient bottom water energy and are characterized by fractures or other interconnected channels with bottom water, which can easily cause high water cut in oil wells during production. The main reasons are as follows: firstly, bottom water coning leads to water flooding. Secondly, artificial water injection flooding fails and shows high water cut in oil production. This paper further clarifies the causes of high water cut in fractured-vuggy carbonate reservoirs and explores rational and feasible management strategies to improve the current water flooding situation and reduce the comprehensive water cut in oil wells. In this paper, numerical simulation technology is used to establish a mechanism model based on the actual reservoir conditions. By comparing the development effects of four bottom water suppression measures, including the adjustment of flow channel, artificial barriers, adjustment of flow potential and gas injection, the optimal measure is selected and the relevant parameters are optimized. Building upon this, further optimization of water injection methods is conducted to explore comprehensive management strategies for enhancing the water flooding effect during high water cut periods. The research demonstrates that bottom water can be effectively inhibited by artificial barriers, leading to an expansion of the swept volume of water injection and achieving the goal of improving the high water cut condition in carbonate reservoirs. Optimal implementation of artificial barriers occurs when the water cut reaches around 80%. Specifically, positioning barriers at the bottom of perforations and setting the barrier radius at 0.15–0.2 times the well spacing obtain the most favorable results. Additionally, short-term injection with long-term shut-in, identified through cyclic water injection simulations, exhibits superior oil recovery enhancement. Validation conducted in a practical field of a fractured carbonate reservoir over a five-year period has led to a substantial increase in oil production by 5.6 × 104 t and a 12% reduction in water cut. The research approach and methodology presented in this paper can provide valuable insights and serve as a reference for the development of high water cut periods in fractured-vuggy carbonate reservoirs.

A Putative Role of Vasopressin/Oxytocin-Type Neuropeptide in Osmoregulation and Feeding Inhibition of Apostichopus japonicus.

Vasopressin/oxytocin (VP/OT)-type neuropeptide is an ancient neurophysin-associated neuropeptide and has been intensively studied to be involved in multiple physiological processes in protostomian and deuterostome vertebrates. However, little is known about the functions of VP/OT-type neuropeptide in deuterostome invertebrates especially in echinoderms. Here, we firstly report VP/OT-type neuropeptide signaling in an important economic species, Apostichopus japonicus, which is widely cultured in Asia, with high nutritional and medicinal values. Molecular characterization analysis of holotocin and its precursor revealed the highly conserved features of VP/OT family. The candidate receptor for holotocin (AjHOR) was confirmed to be able to activate the signaling via cAMP-PKA and possible Ca2+-PKC pathway, and further activated the downstream ERK1/2 cascade. Holotocin precursor expression profile showed that they were mainly concentrated in circumoral nerve ring. Furthermore, in vitro pharmacological experiments demonstrated that holotocin caused contractile responses in preparations from A. japonicus. And in vivo functional studies indicated that short-term injection of holotocin resulted in body bloat and long-term injection resulted in reduced body mass, suggesting potential roles of holotocin in osmoregulation and feeding co-inhibition with holotocin-CCK. Our findings provided a comprehensive description of AjHOR-holotocin signaling, revealed ancient roles of holotocin in osmoregulation and feeding inhibition by controlling muscle contractions.

Thermal-Hydraulic-Mechanical (THM) Modelling of Short-Term Gas Storage in a Depleted Gas Reservoir—A Case Study from South Germany

This study addresses the use of former gas storage facilities as short-term storage for renewable energy through power-to-gas (PtG) technology in Germany. Three test cases with coupled thermal-hydromechanical (THM) modelling were conducted to evaluate short-term injection and production schedules. The operating rates were controlled by the upper and lower limits of the wellbore pressure. The maximum difference in pore pressure and effective stress was 0.6 MPa in all cases. Fault reactivation analysis was performed on the THM models to estimate fault stability. The critical pore pressure for safe reservoir operation was determined to be 1.25 times the original pore pressure, corresponding to a WBHP value of 20.25 MPa. The upper limit of the gas injection rate for safe storage operation was estimated to be between 100,000 and 150,000 m3/day. The thermal stresses were found to be negligible for short-term cases. The storage capacity of PtG technology was reported to be up to 1,322,400 kWh/d of renewable electricity, which can contribute to Germany becoming a greenhouse gas neutral country by 2050. The workflows and results of the study are applicable to all gas storage in a porous medium, including methane, CO2, and hydrogen.

Abstract 15540: Single Cell Transcriptional-Epigenetic Profiling and Sub-Cellular Proteomics Demonstrate That HIV-Nef Extracellular Vesicles Modulate Human Macrophage Heterogeneity to Promote Atherosclerosis

Background: In the era of modern Anti-Retroviral Therapy, people living with HIV continue to remain at a higher risk than the general population for cardiovascular diseases including atherosclerosis. We hypothesized that circulating extracellular vesicles (EV) containing HIV-Nef protein promote inflammation by switching the pattern of macrophage heterogeneity towards a pro-inflammatory state that underlies cardiovascular disease. Methods & Results: Human primary macrophages were stimulated with EV engineered to contain HIV-Nef. Macrophage heterogeneity was characterized by simultaneous single cell mRNA-seq and single cell ATAC-seq integrated with WNN mapping in 50,931 cells. Among 16 clusters (Fig. A), pseudotime (Slingshot), gene regulatory (DoRothEA and SCENIC) and transcription factor motif accessibility (ChromVar) analyses demonstrated that HIV-Nef regulates 3 inflammatory clusters as gauged by differentially active and accessible transcription factors, e.g., JUN, YY1 and STAT1. Sub-cellular proteomics identified differentially abundant proteins associated with DNA (662 proteins), nucleus (261), cytosol (461), cell surface (72) and EV (132). Pathway enrichment analysis of these proteins revealed changes in biological processes in immune responses, cytoskeletal regulation, and metabolism. Functional phenotyping showed HIV-Nef shifts macrophages towards a pro-inflammatory phenotype by suppressing atheroprotective efferocytosis, promoting chemotaxis and altering metabolic state. Furthermore, short-term injection of HIV-Nef EV into WT mice induced inflammatory chemokine secretion, while long-term injection into Ldlr -/- mice enhanced atherogenesis (Fig.B). Conclusions: Persistent Nef in EV of HIV survivors may modulate macrophage heterogeneity to promote chronic inflammation. These findings may help identify patients at risk for cardiovascular complications and develop novel atheroprotective therapies.

HIV Promotes Neurocognitive Impairment by Damaging the Hippocampal Microvessels.

Current evidence suggests that mild cerebrovascular changes could induce neurodegeneration and contribute to HIV-associated neurocognitive disease (HAND) in HIV patients. We investigated both the quantitative and qualitative impact of HIV infection on brain microvessels, especially on hippocampal microvessels, which are crucial for optimal O2 supply, and thus for maintaining memory and cognitive abilities. The results obtained using cultured human brain microvascular endothelial cells (HBMEC) were reproduced using a suitable mouse model and autopsied human HIV hippocampus. In HBMEC, we found significantly higher oxidative stress-dependent apoptotic cell loss following 5h of treatment of GST-Tat (1µg/ml) compared to GST (1µg/ml) control. We noticed complete recovery of HBMEC cells after 24h of GST-Tat treatment, due to temporal degradation or inactivation of GST-Tat. Interestingly, we found a sustained increase in mitochondrial oxidative DNA damage marker 8-OHdG, as well as an increase in hypoxia-inducible factor hypoxia-inducible factor-1α (HIF-1α). In our mouse studies, upon short-term injection of GST-Tat, we found the loss of small microvessels (mostly capillaries) and vascular endothelial growth factor (VEGF), but not large microvessels (arterioles and venules) in the hippocampus. In addition to capillary loss, in the post-mortem HIV-infected human hippocampus, we observed large microvessels with increased wall cells and perivascular tissue degeneration. Together, our data show a crucial role of Tat in inducing HIF-1α-dependent inhibition of mitochondrial transcriptional factor A (TFAM) and dilated perivascular space. Thus, our results further define the underlying molecular mechanism promoting mild cerebrovascular disease, neuropathy, and HAND pathogenesis in HIV patients.

Comparing Benzodiazepines-morphine-induced Respiratory Depression by Analyzing Respiratory Pattern in Rats

Background and Aim: Opioid and benzodiazepine family drugs are concurrently used in various patients. Considering the respiratory depressant effects of both classes, in this study, we investigated the effect of coadministration of morphine and several widely used benzodiazepines in the clinic on the rate of respiratory depression in rats. Methods & Materials: Seventy adult male Wistar rats were randomly divided into 10 groups; morphine, midazolam, diazepam, lorazepam, alprazolam, morphine-midazolam, morphine-diazepam, morphine-lorazepam, and morphine-alprazolam. Respiration signal was recorded using whole-body plethysmography 15 minutes after the intraperitoneal injection of the drugs. The respiratory pattern was examined using several parameters; the mean value of inter-breath interval and the respiratory rate, as well as the coefficient of variation and sample entropy analysis of inter-breath interval. Ethical Considerations: This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1397.327). Results: Analyzing respiratory data revealed that injecting the anxiolytic dose of alprazolam, and the combination of morphine-alprazolam and morphine-midazolam, altered the respiratory pattern. Such changes were associated with a decrease in the number of breaths and an increase in the inter-breath interval in the explored test animals, compared with the controls. The obtained data also indicated that morphine-midazolam injection increased the variability of the breathing pattern; such an alternation was associated with increased irregularity and decreased coefficient of variation of the inter-breath interval. Conclusion: The present research results suggested that the short-term injection of morphine-midazolam changes the respiratory pattern more severely than morphine combined with other benzodiazepines.

Roles of gonad-inhibiting hormone in the protandric simultaneous hermaphrodite peppermint shrimp†.

To date, the molecular mechanisms of the unique gonadal development mode known as protandric simultaneous hermaphroditism (PSH) are unclear in crustaceans. In this study, cDNA of a gonad-inhibiting hormone (Lv-GIH1) was isolated from the PSH peppermint shrimp Lysmata vittata, and its expression was exclusively found in the eyestalk ganglion. Real-time quantitative polymerase chain reaction (qRT-PCR) revealed that the expression of Lv-GIH1 increased during gonadal development of the functional male stages but decreased significantly at subsequent simultaneous hermaphroditism stage. Further in vitro experiment showed that recombinant GIH1 protein (rGIH1) effectively inhibited Vg expression in the cultured hepatopancreas tissues while the short-term injection of GIH1-dsRNA resulted in reduced expression of Lv-GIH1 and upregulated expression of Vg in the hepatopancreas. Moreover, long-term rGIH1 injection led to significantly reduced expression of Lv-Vg, Lv-VgR, and Lv-CFSH1, subdued growth of oocytes, and feathery setae as a secondary sexual characteristic in females. Interestingly, while germ cells in testicular part were suppressed by rGIH1 injection, the expression of Lv-IAGs showed no significant difference; and long-term GIH1-dsRNA injection results were contrary to those of rGIH1 injection. Taken together, the results of this study indicate that Lv-GIH1 is involved in gonadal development and might also participate in controlling secondary sexual characteristic development in L. vittata by inhibiting Lv-CFSH1 expression.

Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model.

Background: Funding for product development for neglected diseases fell from 2009-2015, other than a short-term injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact (P2I) financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority "missing" products. Results: We found 685 product candidates for neglected diseases as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range $13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches. Based on the current pipeline, there would be very few launches of complex new chemical entities; launches of highly efficacious vaccines for HIV, tuberculosis, or malaria would be unlikely. Estimated additional costs to launch one of each of 18 key missing products range from $13.6B-$21.8B, depending on product complexity. Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5-5.8B/year. Conclusions: Since current annual global spending on product development is about $3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B, which is probably an underestimate. The current portfolio is not balanced across health needs.

Strengthening Township Economies in South Africa: the Case for Better Regulation and Policy Innovation

There is considerable policy interest in supporting township economies at present. This is important considering their history of marginalization and the extent of unemployment and poverty. However, the short-term injection of additional resources could simply leak out unless more conducive conditions are created for enterprises to grow and develop locally. The paper examines the framework of government laws, regulations and administrative procedures that inhibit township economic development. Inappropriate standards and onerous approval systems make it difficult for firms with growth aspirations and potential to formalize their operations and expand. The current situation oscillates between laissez-faire neglect and enforcement of punitive regulations, which creates uncertainty and opportunities for abuse. The paper concludes with some recommendations to create a more enabling environment, emphasizing the need for local experimentation and learning from reforms to different elements of the regulatory framework.

Pharmacokinetic and pharmacodynamic modeling of gut hormone peptide YY(3–36) after pulmonary delivery

Peptide YY(3–36) (PYY(3–36)) is an endogenous appetite suppressing peptide. The present research was to perform pharmacokinetic/pharmacodynamic (PK/PD) analysis for predicting the concentration- and response-time profiles of PYY(3–36) after systemic and pulmonary delivery in mice, with the goal of suggesting a potential pulmonary dosing regimen in humans. A PK/PD model was developed to describe PYY(3–36) plasma concentration - and relative food intake rate ratio (as % of control) - time profiles after intraperitoneal and subcutaneous administration, and inhalation in mice. The absorption of inhaled PYY(3–36) from the lungs of mice could only be described with a combined slow (absorption rate of 0.147 L/h) and fast (absorption rate of 104.4 L/h) absorption process, presumably related to absorption from the central and peripheral regions of the lungs. The estimates for IC50 and Imax were 6.8 ng/mL and 63.5%, respectively, based on inhibitory Emax model. The PK parameters, such as clearance (CL), volume of distribution at steady state (Vdss), and the absorption rates (ka), were then scaled to human’s. The scaled human CL and Vdss for obese subjects were 24.8 L/h and 9.0 L, respectively. The model predicted human plasma PYY(3–36) concentrations agreed reasonably well with placebo-normalized plasma PYY(3–36) concentrations after short-term infusion and SC injection in literature. An inhalation dose of PYY(3–36) of about 100 µg was proposed for obese subjects based on simulations. This PK/PD analysis satisfactorily described PYY(3–36) concentration-time and relative food intake rate ratio- time profiles at all doses and routes. The developed model might facilitate the inhalation dose selection of PYY(3–36).

Short-term tamoxifen treatment has long-term effects on metabolism in high-fat diet-fed mice with involvement of Nmnat2 in POMC neurons.

Short-term tamoxifen treatment has effects on lipid and glucose metabolism in mice fed chow. However, its effects on metabolism in mice fed high-fat diet (HFD) and the underlying mechanisms are unclear. Here, we show that tamoxifen treatment for 5 days decreases fat mass for as long as 18 weeks in mice fed HFD. Tamoxifen alters mRNA levels of some genes involved in lipid metabolism in white adipose tissue and improves glucose and insulin tolerance as well as hepatic insulin signaling for 12-20 weeks. Proopiomelanocortin (POMC) neuron-specific deletion of nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) attenuates the effects of tamoxifen on glucose and insulin tolerance. These data demonstrate that short-term injection of tamoxifen has long-term effects on lipid and glucose metabolism in HFD mice with involvement of Nmnat2 in POMC neurons.

Resveratrol increases resistance of mouse oocytes to postovulatory aging in vivo.

After ovulation, metaphase II oocytes undergo a time-dependent deterioration in vivo or in vitro, which is referred to as postovulatory oocyte aging, a process during which a series of deleterious molecular and cellular changes occur. In this study, we found that short-term injection of resveratrol (3,5,4'-trihydroxystilbene) effectively ameliorated oxidative stress-induced damage in postovulatory oocyte aging of middle-aged mice in vivo. Resveratrol induced changes that delayed the aging-induced oocyte deterioration including the elevated expression of the anti-aging molecule Sirtuin 1 (SIRT1); it reduced intracellular reactive oxygen species (ROS) level, and improved mitochondria function. In addition, these beneficial changes may also help to prevent apoptosis. Taken together, our data suggest that resveratrol can effectively protect against postovulatory oocyte aging in vivo primarily by preventing ROS production.

Follow-up as analysis tool of the potential long-term effects of SPINK, CTRC mutations in Acute Pancreatitis Patients

To perform a meta-analysis of all available studies on the effect of prophylactic somatostatin administration on prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and post-ERCP hyperamylasemia (PEHA).Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index were searched to retrieve relevant trials. Randomized, placebo-controlled trials in adult patients that compared somatostatin versus placebo in prevention of PEP were included. Meta-analysis was performed using a random-effects model to assess the ratios of PEP, PEHA and post-ERCP abdominal pain.Total ratio of PEP of somatostatin group was significantly lower than that of placebo group. For the short-term injection or bolus injection there were no heterogeneity and no significance between the ratio of PEP of somatostatin group and placebo group. For the long-term injection subgroup there was heterogeneity, and the ratio of PEP of somatostatin group was significantly lower than that of placebo group. There was no significance between the ratio of PEP of somatostatin group and placebo group for the low-risk PEP subgroup, while the ratio of PEP of somatostatin group was significantly lower than that of placebo group for the high-risk PEP subgroup. The ratio of PEP of somatostatin group was significantly lower than that of placebo group for the long-term injection high-risk PEP subgroup. There was no significance between the ratio of PEHA of somatostatin group and placebo group for the short-term injection subgroup or bolus injection subgroup. The ratio of PEHA of somatostatin group was significantly lower than that of placebo group for the long-term injection subgroup. The total ratio of post-ERCP abdominal pain of somatostatin group was significantly lower than that of placebo group. The funnel plot of incidence of PEP and PEHA showed no asymmetry with a negative slope.Prophylactic use of long-term injection of somatostatin can significantly reduce the incidence of PEP, PEHA and post-ERCP abdominal pain for the high-risk PEP patients, while it is not necessary to be used for the low-risk PEP patients.

Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model

Background: Funding for product development for neglected diseases fell from 2009-2015, other than a short-term injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact (P2I) financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority “missing” products. Results: We found 685 product candidates for neglected diseases as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range $13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches. Based on the current pipeline, there would be very few launches of complex new chemical entities; launches of highly efficacious vaccines for HIV, tuberculosis, or malaria would be unlikely. Estimated additional costs to launch one of each of 18 key missing products range from $13.6B-$21.8B, depending on product complexity. Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5-5.8B/year. Conclusions: Since current annual global spending on product development is about $3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B, which is probably an underestimate. The current portfolio is not balanced across health needs.

Electrotransfer of single-chain LH gene into skeletal muscle induces early ovarian development of orange-spotted grouper (Epinephelus coioides)

Luteinizing hormone (LH) plays important roles in regulating steroidogenesis and reproductive development of vertebrates. In the present paper, we study function of LH on early ovarian development of orange-spotted grouper by electrotransfer of single-chain LH gene into skeletal muscle for the first time. Short-term and long-term injection experiments were performed in this work, respectively. For short-term injection experiments, fish received one electrotransfer with the plasmid in skeletal muscle, then blood and muscle around the injected area were sampled 1, 3, 5 and 7 days after the injection, mRNA expression levels of LH gene relative to 18S were determined by quantitative real-time PCR (RT-PCR) assays and serum 17β–estradiol (E2) levels were quantified by ELISA method. The results showed that levels of mRNA of LH gene in muscle and serum E2 level increased from 1 day to 7 days after the injection. For long-term injection experiments, fish received electrotransfer with the plasmid 4 times at weekly intervals in skeletal muscle. 48 h after the last injection, blood, gonad and hypothalamus samples were collected. Transcripts of cyp19a1a, cyp19a1b and gnrh1 genes and levels of serum E2 were separately analyzed by RT-PCR assays and ELISA method, and ovarian tissues were made of paraffin sections and stained by hematoxylin-eosin by method and observed by optical microscopy. The results suggested that long-term injection of LH gene into muscle upregulated transcripts of cyp19a1a and cyp19a1b and downregulated that of gnrh1, and stimulated E2 production and early-stage oogenesis. Moreover, statistical data showed that 9 of 10 ovaries of injected fish with LH gene began to develop after the long-term experiments. These data suggest that single-chain LH gene introduced into skeletal muscle via electrotransfer can be expressed and induce the early ovarian development of juvenile orange-spotted grouper. This work contributes to solve reproductive dysfunctions associated with low hormone levels of teleosts, further it may represent the demonstration at regulation of LH on early ovarian development of orange-spotted grouper to a certain extent.

Short-term injection drug use changes following hepatitis C virus (HCV) assessment and treatment among persons who inject drugs with acute HCV infection

BackgroundIt is unclear whether treatment and care for hepatitis C virus (HCV) infection can help people who inject drugs (PWID) modify their injection drug use behaviours. This study examined changes in injection drug use among PWID with acute HCV systematically referred for HCV clinical assessment and treatment and offered targeted health care services, over the course of one year. MethodsThe study sample included PWID with documented acute HCV infection recruited and followed-up semi-annually at least twice in IMPACT (2007–2015), a longitudinal community-based prospective study in Montréal, Canada. Following enrolment, participants with contra-indications to treatment due to severe co-morbidity were offered targeted health care services. Pegylated interferon-alpha (12–24 weeks) was offered to all other participants who did not spontaneously resolve their infection. At each study visit, data were collected on socio-demographic factors and drug use patterns. Logistic regression was used to assess changes in injection drug use at one-year follow-up. ResultsOf the 87 eligible participants (mean age: 35.6; 78.2% male), 21.8% received treatment [(RT), Sustained virological response: 84.2%], 25.3% spontaneously resolved their infection (SR), 14.9% had contra-indication(s) (CI) and 37.9% chose not to engage in HCV care post-diagnosis (NE). In multivariate analyses adjusting for age, gender and injection drug use at baseline, the RT [Adjusted odds ratio (AOR): 0.18; 95% Confidence interval (CI): 0.04–0.76], SR (AOR: 0.34; 95% CI: 0.08–1.40), and CI (AOR: 0.24; 95% CI: 0.05–1.22) groups were less likely to report injection drug use at follow-up relative to the NE group. ConclusionPWID who received treatment, spontaneously resolved their infection or presented with treatment contra-indication(s) reported reduced injection drug use at one-year follow-up relative to those who did not engage in therapy. Findings suggest that the benefits of HCV assessment and treatment may extent to helping PWID modify their injection drug use patterns.

Investigating the Effects of Ferula Szowitsiana (Ferula szowitsiana L.) on Antioxidant System Parameters in the Hippocampus of Male Rats to Follow Inducemultiple Sclerosis Disease

Introduction: Oxidative stress is resulting from the imbalance between free radicals and antioxidant system of the body. Increased oxidative stress in the brain causes impaired brain activity, neuronal death, and diseases such as multiple sclerosis (MS). In this study, the protective effect of Ferula szowitsiana plant against oxidative stress caused by cerebral ventricular injection of ethidium bromide was evaluated. Materials & methods: With direct single injection of 0.01 % ethidium bromide (EB) into the Cornu ammonis (CA1) of hippocampal formation the induction of MS was done. One week after MS induction, animals received intrahippocampal (5 μg/rat and 10 μg/rat) administration of the extract for 3 consecutive days. At the end, the bilateral hippocampi was dissected and used for the measurement of oxidative stress markers. Statistical analysis of the obtained data was performed using one-way ANOVA. Findings: Hippocampal injection of EB caused significant increment of total antioxidant capacity (p less-than 0.001) and activity of antioxidant enzymes SOD and decrease activity of CAT (p less-than 0.01). Short-term local injection of Ferula szowitsiana extract significantly reduced the total antioxidant capacity (p less-than 0.001) and activity of CAT and SOD enzymes (p less-than 0.001) to the normal levels. Discussion & conclusions: The results of the present study show that local injection of EB cause increasing production of the free radicals. The Ferula szowitsiana extract as a potent antioxidant modulates oxidative stress markers, probably through scavenging of reactive oxygen species )ROS( and clearing of free radicals from the cellular milieu.