IL-17 and IL-10 were click here correlated with each other (r = 0.7, Fig. 2), however the correlations between IL-10 or IL-17 and other cytokines, were weak and negative ( Fig. 2). Adding the “standardised” TH1 responses together (IFNγ, TNFα, IL-1α, IL-6 and IL-2), and calculating the correlation with the “standardised” IL-10 response, gave a correlation coefficient of −0.4, which was considerably larger in magnitude than any of the individual correlations between a TH1 cytokine and IL-10. From the principal components analysis, 90% of the total variation in the responses of the 15 cytokines could be summarised by 5 components. The first component alone accounted for 49% of the total variation

and corresponded approximately to the average of the “standardised” log responses to IFNγ, IL-1α, IL-2, IL-6, TNFα, IL-5, IL-13, IL-8, MIP-1α, G-CSF and GM-CSF. The second component is independent of the first one, and describes a further 20% of the remaining variation and corresponded approximately to the average of the “standardised” log response to IL-4, IL-5, IL-10, IL-17 and IP-10 Cabozantinib molecular weight (Table 3). Using the two components to explain the variation within the 15 cytokines included, the vaccinated

and unvaccinated infants were clearly separated into two groups and also the variation among individuals who were vaccinated was much more simply summarised (Fig. 3). Principal component analysis of the five pro-inflammatory cytokines measured showed that 73% of the total variation could be explained by the first component, and this corresponded approximately to the average “standardised” response to the 5 cytokines. We have previously shown that BCG vaccinated infants in the UK made IFNγ to M.tb PPD in 6-day diluted whole blood cultures, while unvaccinated infants did not make a detectable IFNγ response [6]. The Multiplex assay enabled us to test for multiple cytokines in the same supernatant sample,

and 6 out of the 21 cytokine responses tested showed no evidence of a difference in production between the vaccinated and unvaccinated infants. These included IL-12p70, IL-1β, IL-15, Eotaxin, Farnesyltransferase and IL-7 which were present in very low to undetectable concentrations in supernatants of stimulated cultures for both vaccinated and unvaccinated infants. This may be due to the cytokines not being produced in M.tb PPD stimulated cultures during the 6 days of culture at this time point since vaccination, i.e. at 3 months post-BCG vaccination, to their being produced but not remaining in the supernatant for the 6 days of culture, or to their being produced at levels undetectable by the Multiplex assay despite the increased sensitivity of this assay compared to ELISA. Responses to MCP-1 were seen in both vaccinated and unvaccinated infants and may reflect non-mycobacterial specific responses.

The combined study based on the computational and experimental techniques helped in identifying novel inhibitors that bind to SAM binding site.21, 22 and 23 The present work is to identify the inhibitor lead molecules for Flavivirus NS5 MTase using computational approach. The

dengue MTase has separate binding sites for RTP and SAM. E-pharmacophore studies were performed using both the sites for studying the substrate and inhibitor binding in the active site of MTase. Finally, these pharmacophores were used as queries for virtual screening using compounds from the Asinex database and induced fit docking (IFD) was carried out for the short-listed compounds. The identification of pharmacophore features

was carried out by aligning all the compounds together in a 3D Cartesian space. The earlier studies focused on the structure-based selleck products virtual screening and ligand-based pharmacophore models, keeping the active site of the protein rigid.18, 19 and 20 AZD2281 research buy The structure-based pharmacophore was used to derive pharmacophore features from the inhibitors or substrates that bind at different sites, separately. The X-ray crystal structures of the dengue MTase complex, MTase–SAM complex (PDB id: 3P97), MTase–SAH complex (PDB id: 1R6A), MTase–RTP complex (PDB id: 1R6A) specific to the Flavivirus were retrieved from Protein Data Bank. 25 During protein preparation, water molecules were removed, hydrogen atoms were added, bond orders were assigned and orientation of hydroxyl groups were optimized. Energy minimization was carried out using OPLS2005 force field to converge RMSD of 0.30Å. The receptor grid was generated around the centroid of the ligand contained by enzyme file and the ligands with cut off size of 10 Å were allowed to dock. The ligands were docked with the active site using the ‘Extra Precision’ Glide algorithm. 26 and 27 Glide includes ligand–protein interaction energies, hydrophobic interactions,

hydrogen bonds, internal energy, π–π stacking interactions and root mean square deviation (RMSD) and desolvation. Finally, best pose of the particular ligand was selected based on the Glide crotamiton score. Energy-optimized pharmacophores (e-pharmacophores)28 were evaluated through mapping the energetic terms from the Glide XP scoring function onto atom center. Pharmacophore sites were automatically generated from the protein–ligand docked complex with Phase (Phase, v.3.0, Schrodinger, LLC) using the default set of six chemical features, hydrogen bond acceptor (A), hydrogen bond donor (D), hydrophobic (H), negative ionizable (N), positive ionizable (P), and aromatic ring (R). Glide XP descriptors include terms for hydrophobic enclosure, hydrophobically packed correlated hydrogen bonds, electrostatic rewards, π–π stacking, π cation and other interactions.

Furthermore, management of this condition depends on symptoms and the function of the renal moieties. If the patient is asymptomatic or has minimal symptoms, as in our case, no treatment is required, but regular follow-up may be advised. On the other hand, if the kidney is diseased or nonfunctional,

nephrectomy is usually the preferred procedure.5 Although supernumerary kidney is much more likely to be accompanied with other anomalies of the urinary tract, making this diagnosis per se is not an indication for any intervention. “
“Renal subcapsular hematoma is uncommon in the clinical setting. The case we report in this study was of a large subcapsular hematoma in the renal hilum and collecting area and it was the only case treated in our hospital Trichostatin A to date. The upper segment of the ureter was compressed by the large subcapsular hematoma, and a section of the hematoma separated away and lodged in the renal collecting area,

leading to severe hydronephrosis of the left kidney. This condition is very rare and difficult to diagnose clinically and with radiologic imaging. We summarized the imaging check details features and analyzed the factors leading to the misdiagnosis of hydronephrosis in this case. A 26-year-old man was admitted to our hospital for pain in the left flank with no obvious cause. The patient had no fever, abdominal pain, nausea, or hematuria. Physical examination revealed bilateral lack of flank swelling and no tenderness on percussion, nonpalpable kidneys, no deep tenderness bilaterally in the region of the ureters, no swelling over the bladder, or tenderness and palpable mass on palpation. Laboratory test results were as follows: urine white blood cell count, 2.30/μL; peripheral blood: erythrocyte count, 16.10/μL; white blood cell count, 7.25 × 10−9/L; platelets, 118.0 × 10−9/L. Ultrasonographic examination revealed left kidney hydronephrosis, and left renal retrograde

urography revealed severe dilatation of the left upper ureter and hydronephrosis (Fig. 1). Abdominal computed tomography (CT) scan also revealed severe left renal hydronephrosis (Fig. 2). Tryptophan synthase Surgery revealed left perirenal fat hypertrophy with diffuse inflammatory adhesions associated with the kidney capsule. The left ureter was considered normal. The entire pelvic wall was thin with elevated intrarenal pressure. The renal cortex was pouch-shaped, and incising the left kidney pole, 450 mL of dark red effusion was released. Pathologic analysis confirmed a diagnosis of kidney subcapsular hematoma with separation of the main section of the hematoma entering the renal collecting area (Fig. 3). The upper segment of the left ureter was compressed by the large subcapsular hematoma, leading to severe hydronephrosis of the left kidney. Renal subcapsular hematoma is a type of hematoma located between the renal capsule and renal parenchyma, and it is because of the rupture of blood vessels of the kidney or renal capsule.

Subclinical infection of vaccinated pigs has been reported,

but other vaccinated pen-mates showed disease [33]. Studies on experimentally infected pigs showed that there is a rather short duration of NSP seroreactivity in infected pigs with declining levels of reactors after 9 weeks [40]. If the serosurvey aimed at demonstrating freedom from FMD finds evidence of NSP reactors within herds, then following retesting and use of confirmatory tests, the number and strength of the seroreactors will influence the degree of suspicion that infection occurred [49]. It can be argued that if farm visits for the initial collection of serum samples have already included careful inspection of all the animals without buy MG-132 finding any signs of disease and if isolated NSP positive reactors are subsequently found at a level consistent with that expected (from the known specificity of the test used) there should not need to be any follow-up visits for inspection and resampling/testing as

prescribed in the OIE Code and the EU Directive [9] and [19]. Other factors that would mitigate against the need for a follow-up farm visit include the availability of location data for individual animals to rule out clustering of positive cases, samples originating from pigs that do not become long-term virus carriers PD98059 and only weak positive test reactor findings. Such decisions need to be taken on a case-by-case basis. If the level of suspicion warrants a follow-up visit, this should check for clinical signs and clustering of positive animals and to examine and resample the initially seropositive Florfenicol animals along with in-contact animals. If clinical or epidemiological evidence for infection or disease were then found, the usual measures for investigating a suspect case would be followed. Past infection would be distinguished from non-specific reactors by presence or absence

of clustering and by the number and strength of seroreactors relative to that predicted from the known specificity of the test [55]. Recent infection would be confirmed by clinical checks and/or evidence of seroconversion from the second round of sampling [19] and [56]. IgM tests could also be helpful in this situation [57]. Oral or nasal swabs could be collected from pigs and oesophagopharyngeal fluids collected from ruminants for virological testing to look for evidence of infection [58]. However, the virological techniques have low sensitivity whilst a false positive test finding could be difficult to identify. Use of an IgA test has been proposed as a proxy for the probang virus test [59] and [60] as FMDV-specific IgA antibody in mucosal secretions of the upper respiratory tract of cattle is mainly associated with the continued presence of detectable virus in a probang cup sample. However, despite the potential logistic advantages, the IgA test is not yet commercially available.

“
“Rapid reperfusion with percutaneous coronary intervention (PCI) is the gold standard therapy for patients presenting with ST-segment elevation myocardial infarction (STEMI) when promptly available [1]. Delays in door-to-balloon (DTB) times correlate with increased morbidity and mortality [2] and [3]. Achieving a DTB time of < 90 minutes has become a quality measure of the hospital system performance dealing with STEMI care [1] and [4]. With the identification of key strategies to enhance hospital system performances [5] and [6], several programs have been successfully implemented

to help meet the DTB < 90-minute time goals with timely access to primary PCI [7], [8] and [9]. To address the continuum of care for STEMI patients from the onset of symptoms to arrival at the emergency department (ED), the use of emergency medical services (EMS) may BMS-754807 molecular weight potentially facilitate rapid transport, early assessment and treatment, and expedited communication

of information GDC-0449 in vivo with the accepting ED. However, EMS has been shown to be underutilized [10] and [11], and a significant proportion of STEMI patients still arrive at the ED via their own transportation. MedStar Washington Hospital Center (Washington, DC) is a primary PCI facility with around-the-clock cardiac catheterization capabilities catering to Washington, DC, a highly urbanized area with EMS coverage provided fully by the DC Fire and EMS. In addition, it serves as a referring PCI center for other facilities in DC, as well as parts of Maryland and Virginia. MedStar Washington Hospital Center is located in the heart of Washington, DC, and with DC Fire and EMS as the single EMS provider for Washington, DC, this offers us a unique opportunity to analyze

modes of transport for STEMI patients within DC, and its impact on pre- and in-hospital care processes leading to reperfusion. Specifically, we aimed to determine if the use of EMS transport may actually reduce overall DTB times by reducing certain components of in-hospital processing times. This retrospective analysis included all patients from January 2007 to December 2012 who presented to the MedStar Washington Hospital Center ED with a STEMI and subsequently underwent primary PCI. Patients who were transferred from a referring institution, patients who suffered cardiac arrest, patients who were intubated, Terminal deoxynucleotidyl transferase and patients who were given fibrinolytic therapy before the PCI were excluded. The patients were categorized into whether they were self-transported (“self”) or transported by EMS. DC Fire and EMS provides EMS coverage to Washington, DC, an urban city of 68.3 square miles, through 58 medical units (or ambulances) and is managed by a centralized 911 dispatch call system. The ambulances have 12-lead electrocardiogram (ECG) capabilities that are transmissible to the receiving ED at MedStar Washington Hospital Center. All patients are transported to the ED where a formal ECG is performed.

Despite encouragement from the medical professions, most people fail to meet the most minimal level of daily exercise that would prevent the

deleterious effects of hypomobility (American Diabetes Association 2008, Tudor Locke et al 2000, Wei et al 2000). Thus, the finding that static stretching has the potential to be selleck screening library a viable treatment for hyperglycemia provides an alternative treatment modality in the absence of the patient’s desire to exercise. In addition, stretching skeletal muscles similarly to that demonstrated in this study is a hopeful alternative to exercise for those patients with Type 2 diabetes who are too disabled to exercise. Some patient groups that could benefit from a stretching program for improved glucose control might be patients who have sustained a spinal cord injury, patients who have New York Class III/IV rheumatoid arthritis, stroke patients, and those individuals who are constrained to long term bed rest. As physical therapists and nurses interact with these hypomobile patients, 20–40 minutes of passive static stretching could be incorporated into the patient plan of care. Also, many nursing homes do not have a policy to evaluate the effectiveness of a treatment algorithm in their resident population with diabetes to determine if the staff is able to control the glucose peaks and nadirs in these patients (Feldman et al 2009). Few nursing homes, for example, have a policy to evaluate

the Selleck PD-1/PD-L1 inhibitor 2 patient’s HbA1c values routinely (Feldman et al 2009), a

fundamental recommendation by the American Diabetes Association (2008). Failure to control blood glucose levels adequately in the diabetic population represents nearly 50% of all deaths in nursing homes (Russell et al 2005). If a stretching program (either passive or active) under the supervision of a physical therapist or other trained personnel was established, these patients could realise better blood glucose control and health at a substantial financial saving. We acknowledge that this study looked only at the immediate effect of stretching Bay 11-7085 and did not ascertain if this effect could be carried over successive days of stretching. Nevertheless, Kokkonen and colleagues (2007) have shown that a program of 40 minutes static stretching done three times a week can increase muscle strength and endurance. In addition, Nelson and colleagues (2005) have presented data showing that static stretching raises the metabolic rate similar to the rate estimated for walking 40 m/min. These findings, coupled with the results of this study, suggest that stretching daily for 20–40 min may help a person to control or lower blood glucose levels. In conclusion, this study shows that static stretching is an additional viable activity that can help regulate blood glucose acutely. Since it requires little effort by the individual, it appears to be an advantageous treatment for those with reduced physical capabilities.

Central venous catheters, contributing to IVC thrombus in most cases reported here, should be inserted only if necessary. Despite no renal insufficiency at present time, follow-up of this patient HIF-1 activation is mandatory. “
“Ectopic ureter is an anatomic variant, where the ureteral orifice is located at a location other than the posterolateral aspect of the trigone of the bladder.1 This is more common in females than males, at a ratio of

approximately 6:1.2 Male ectopic ureters most commonly insert into the posterior urethra. The most common sites of this anomaly in a female are the urethra, vestibule, and vagina.3 Females most often present with incontinence because the opening is often distal to the external sphincter.2 Other presentations include infection, hydronephrosis, or reflux.4 A duplex collecting system is present in 80% cases of ectopic ureter.5 A 39-year-old woman presented with frequent urinary tract infections for approximately 3 years. She had a previous C59 wnt molecular weight diagnosis of right-sided grade-IV vesiculoureteral reflux with right hydronephrosis resulting in a nonfunctioning right kidney. A computed tomography scan showed right cortical atrophy with dilatation

of the right ureter, with minimal contrast entering the intrarenal collecting system. She then underwent a right laparoscopic radical nephroureterectomy via a transperitoneal approach to remove the chronically infected kidney. Midway through the case and in the postoperative area, the patient became anuric despite adjustment and replacement of the Foley catheter. After a short time, the patient Megestrol Acetate was taken to the cystoscopy suite. Immediately after the cystoscope was introduced into the urethra, 2 openings were noted. The left opening, as expected, led directly into the bladder. However, the right opening lead directly into the ureteral stump, demonstrating the insertion of an ectopic ureter. No right ureteral orifice was found opening into the bladder, making it a single ectopic system (Fig. 1).6 A Foley was placed in the bladder using a guidewire under cystoscopic visualization and urine was evacuated. The patient has had no complications since the procedure.

The patient presented in this case is unique for several reasons. Initially, the patient was diagnosed with right-sided grade-IV vesiculoureteral reflux, which by definition is incorrect because of the absent direct connection of the bladder to the ectopic ureter. Despite multiple cystoscopies and contrast computed tomography scans during the workup, the abnormality was difficult to identify. Also, considering this patient’s anatomy, incontinence much earlier in life would have been expected to be the presenting and most severe symptom. The patient had complaints of incontinence in her teenage years, which had since resolved; however, it was significantly overshadowed by her frequent urinary tract infections. The incidental method of finding the correct diagnosis was also distinctive.

However, increasing FITC loading (F9–F11) particularly at the 20% w/w level was associated with a marked increase in particle size and PDI and reduced zeta potential. The FITC NPs formulation (F12) prepared using 1% w/v PVA as stabilizer showed a zeta potential of −4.5 and a distinct increase in particle size. Fig. 3 shows TEM images of representative Rh B (F8) and FITC (F9) NPs samples prepared using PLGA 50:50 at 5% w/w dye loading. NPs were spherical in shape with more or less uniform size verifying size data presented PDGFR inhibitor in Table 1. Data for skin permeation of nanoencapsulated

dyes across MN-treated porcine ear skin, expressed as cumulative amount of dye permeating at 48 h (Q48, μg/cm2) and steady state flux (μg/cm2/h), are presented in Table 2. Several reports provided

evidence for maintenance of the barrier function of porcine skin for up to 48 h [10] and [31]. Further, frequent sampling was essential for the initial part of the study due to the lack of the literature data regarding the permeation of a dye loaded into nanoparticles through MN-treated skin. At the 1% w/v DMAB concentration used throughout the study, NPs had a mean diameter of approximately http://www.selleckchem.com/products/Romidepsin-FK228.html 100 nm (Table 1) which did not noticeably change in response to homogenization speed (screening data not shown). The higher concentrated 3% w/v DMAB solution had a higher viscosity (20.8 ± 0.0026 cP) as measured using a cone and plate viscometer (CSL2 others 100, TA Instruments, Crawley, UK) compared to that of the

1% w/v solution (3.71 ± 0.0004 cP). It resulted in a measurable increase in particle size that was inversely proportional to the homogenization speed. Thus, NP size was controlled by optimizing emulsion homogenization speed and DMAB concentration (Table 1). The increase in particle size of Rh B-loaded PLGA 50:50 NPs significantly (P < 0.05) reduced Rh B skin permeation ( Fig. 4) despite the PDI values exceeding 0.2. Mean Q48 values of 2.49 ± 0.08, 2.02 ± 0.11 and 0.5 ± 0.20 μg/cm2 and flux values of 3.55 ± 0.09, 2.83 ± 0.19 and 0.81 ± 0.28 μg/cm2/h were obtained for test NPs formulations F1 (155.2 nm), F2 (251.5 nm) and F3 (422.3 nm), respectively. The increase in hydrophilicity of Rh B-loaded PLGA NPs (F4–F6) of more or less similar size (91.9–105.5 nm), achieved by reducing lactide to glycolide ratio, enhanced dye permeation across MN-treated skin (Fig. 5). Data in Table 2 indicated that exposure of skin samples to F4 NPs (PLGA 100:0) resulted in a mean Q48 of 2.07 ± 0.19 μg/cm2 and flux of 2.90 ± 0.27 μg/cm2/h. Reducing the lactide to glycolide ratio to 75:25 (F5) increased Q48 (2.92 ± 1.32 μg/cm2) and the flux (3.98 ± 1.62 μg/cm2/h) yet not significantly (P = 0.379, 0.395, respectively). A further reduction in the lactide content (50:50, F6) caused a significant increase in mean Q48 (5.40 ± 0.39 μg/cm2, P = 0.016) with no significant increase in flux (6.19 ± 0.77 μg/cm2/h, P = 0.072).

The intervention involved scanning the following vaccines labeled with 2D barcodes containing GTIN, lot number, and expiry date: Pediacel® (Diphtheria, Acellular Pertussis, Tetanus, Polio, Haemophilus influenzae type b), Quadracel® (Diphtheria, Tetanus, Acellular Pertussis, Polio), Adacel® (Tetanus, Diphtheria, Acellular Pertussis), Td Adsorbed (Diphtheria, Tetanus), Adacel®-Polio (Tetanus, Diphtheria, Acellular Pertussis, Polio), and Vaxigrip® (Influenza). All vaccines used are listed in Table 1. We compared the collection of vaccine data (vaccine name, lot number, and expiry date) by: (1) barcode scanning of vaccine vials with 2D barcodes

SNS-032 concentration (listed above); and (2) existing methods of entering vaccine information into the electronic systems for non-barcoded vials. We used post-immunization chart audits, time-and-motion studies, observation recording, and telephone interviews to compare the data collection approaches. We received ethics approval from the Health Sciences Research Ethics Board at the University of Toronto, Canada. The study was performed in Algoma

Public Health (APH), one of the 36 local public health units in Ontario, Canada. APH serves a population of 115,870 (2011) [15], delivering the majority of vaccines in Sault Ste. Marie, Ontario and the surrounding see more area through two general weekly immunization clinics (∼100 to 160 vaccines administered per week) (personal communication, Susan Berger, APH). Routine childhood and adult vaccines are given as well as travel-related vaccines. We recruited Intrahealth Canada Ltd., a British Columbia-based electronic medical record (EMR) vendor who added barcode scanning functionality to their Profile software system so that their client APH could participate (Profile immunization screen shown in Fig. 2) [16]. For barcoded vaccines, the immunizers scanned the vial to populate the client’s record with the vaccine information (name, lot number, expiry date). For non-barcoded vaccines, the immunizers used Profile’s conventional method of science recording

vaccine information using drop-down menus that included all vaccines in inventory. Immunization staff were provided with scanners (DS4208-HC Scanner, Motorola Ltd., United States, $260 CAD) with stands (Intellistand for DS42xx series, Motorola Ltd., United States, $39), and each nurse was trained on a one-on-one basis using dummy vials by an APH staff member who was experienced with barcode scanning. Our second study site was First Nations (FN) communities in Alberta. Those belonging to First Nations are Aboriginal people in Canada who are neither Inuit nor Metis (having Aboriginal and European heritage) [17]. Research agreements were developed with four First Nations communities to conduct full or partial data collection: Siksika Nation (on-reserve population [2011], 2858), Stoney First Nations (on-reserve population, 407), Kehewin First Nation (on-reserve population, 900), and Cold Lake First Nations (on-reserve population, 1235) [18].

The RV144 vaccine trial demonstrated modest success, leading to a 31% lowered rate of HIV-1 infection in a specific BIBW2992 ic50 subset of vaccinees versus placebo groups [14]. While the correlates of immunity of that trial remain to be understood, viral diversity is likely to be at least partially responsible for the limited coverage. HIV-1-specific CD4+ T helper cells and CD8+ cytotoxic T cells have been

shown to play a central role in control of the virus following infection [15], [16], [17], [18], [19], [20] and [21]. CD4+ T helper cells are essential for the generation of both humoral and cellular responses against the virus [22] and [23], while cytotoxic T cells play an important role in the resolution of acute viremia and in control of persistent

HIV-1 viral replication [17] and [24]. Recent longitudinal studies following first CD8+ CTL responses to founder virus in early infection have defined a narrow window of opportunity for the CTL response to control infection and revealed multiple evolutionary pathways utilized by the virus during acute infection to retain replicative fitness [25], [26], [27] and [28]. Moreover, roles for both cytolytic function of CD8+ T cells during nonproductive infection and noncytolytic functions (e.g., MIP-1β, MIP-1α, IFNγ, TNFα, and IL-1) in resolution of peak viremia have been identified [29] and [30]. Therefore, vaccines that stimulate

virus-specific T-cell responses may be PLX4032 price able to boost humoral immune responses and may also delay the progression of HIV-1 to AIDS in infected individuals. A robust T-cell response will be a necessary component of any successful HIV vaccine; however, the ability of a vaccine to account for the extraordinary viral diversity of HIV-1 continues to be a challenge. This diversity extends not only to T-cell epitope differences across clades, but also to isolates from a number of diverse clades that occupy a single geographic area [31]. One approach 17-DMAG (Alvespimycin) HCl to address the problem of HIV-1 diversity is to develop multiple vaccines. These vaccines could be developed on a clade-by-clade basis, whereby a single vaccine represents isolates from a single clade, or on a geographically specific basis, whereby vaccines are derived from isolates commonly circulating in a particular country or region. However, this multiple vaccine approach raises the question of how many vaccines would be needed to protect against each of the many clades of HIV. In a time of increasing global connectedness and mobility, the notion of controlling a particular viral population and keeping it geographically sequestered is unlikely to bear fruit. In contrast to region-specific vaccine efforts, our approach is to develop a globally effective vaccine.