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PubMed1996

Motor evoked potentials during brain surgery.

In order to obtain a robust method for intraoperative monitoring of motor pathways, different stimulation patterns to elicit muscle motor evoked potentials (MEPs) were studied during neurosurgical procedures in 3 patients. MEPs were recorded by a catheter electrode in the subdural space and/or by needle electrodes in limb muscles. For stimulation single pulses and trains consisting of two to five pulses were used. Muscle MEPs were only obtained after trains of at least 3 stimuli while single/double stimuli were inefficient. Simultaneous subdural recordings showed that single and double stimuli only elicited D-waves, whereas trains of 3 or more stimuli generated I-waves, as well. We propose that train stimulation can overcome the depressive effects of anesthesia on cortical motoneurons.

Brain↗
PubMed2002

Transcriptional responses of the rat vasopressin gene to acute and repeated acute osmotic stress.

To determine the impact of hypertonic saline administration upon rat arginine vasopressin (AVP) gene transcription in supraoptic nucleus neurons, a probe complementary to the first intron (AVP1) of AVP was used to measure changes in AVP heteronuclear RNA (hnRNA) levels. Animals that received hypertonic saline had increases in AVP1 after 15 and 30 min, with a return to baseline levels by 180 min. In a double injection paradigm, animals were given an injection of normal or hypertonic saline followed 180 min later by a second injection of normal or hypertonic saline and sacrificed 30 min later. When both injections were hypertonic saline (H-H), AVP1 levels were greater than levels seen after a single hypertonic saline injection, or after an injection of normal saline followed by a second injection of hypertonic saline (N-H). This study shows acute, repeated exposure to hypertonic saline causes a robust increase in vasopressin gene transcription. Since a second hyperosmotic stimulus is known to increase neuronal firing rate and activity, our results suggest that a correlation exists with intracellular mechanisms regulating vasopressin gene transcription.

Acute Disease↗
PubMed2006

FRET-CLSM and double-labeling indirect immunofluorescence to detect close association of proteins in tissue sections.

It is pivotal to identify protein-protein interaction in situ to understand protein function. Conventional methods to determine the interaction of proteins destruct tissue or are applicable to cell culture only. To identify association of proteins in cells in tissue, we adapted indirect double-labeling immunofluorescence and combined it with conventional confocal laser scanning microscopy (CLSM) to measure fluorescence resonance energy transfer (FRET). As a model system, we chose caveolin-1alpha and caveolin-2, two major components of endothelial caveolae, and examined their interaction in the endothelium of vessels in fixed tissues of laboratory animals and human glomus tumors. Several methodological aspects were examined. Measuring the absolute increase in fluorescence (DeltaIF) was superior compared to determining the relative FRET efficiency, because it is more robust against small increases of fluorescence during measurements that results from unavoidable minimal crossreactivity of the secondary antibodies. Both, sequential and simultaneous incubation of secondary antibodies result in robust and reliable increases in DeltaIF. If incubated sequentially, however, the acceptor-labeled secondary antibody should be applied first. The size of the secondary reagent (F(ab')2 vs whole antibody) has no major influence. In conclusion, CLSM-FRET can measure close spatial association of proteins in situ and can be applied to human surgical material.

Animals↗
PubMed2001

Sexual dimorphism among bovine embryos in their ability to make the transition to expanded blastocyst and in the expression of the signaling molecule IFN-tau.

IFN-tau is a secretory product of trophectoderm of cattle, sheep, and their relatives and is expressed for a few days in early pregnancy after the blastocyst first forms. It serves to alert the mother that she is pregnant. A delayed or less than robust IFN-tau signal is a likely cause of embryonic loss. Here we have determined whether blastocyst production of IFN-tau, which is encoded by a cluster of genes on chromosome 9, differs between the sexes in cattle, as assessed by culture of in vitro-derived embryos on two different media, one complex (tissue culture medium 199 supplemented with serum) with coculture support, the other relatively simple (synthetic oviductal fluid plus albumin). With both media, female blastocysts produced approximately double the amount of IFN-tau as males, regardless of such variables as oocyte batch, blastocyst quality, hatching, and length of time in culture. However, in either tissue culture medium 199, which contains 5.5 mM d-glucose, or in synthetic oviductal fluid, in the presence but not in the absence of added glucose, significantly fewer female than male embryos were able to progress from the morula/early blastocyst stage to more advanced stages of development. It is possible that the differences between male and female embryos both in their production of IFN-tau and in their ability to progress in development in glucose-rich media are manifestations of phenomena that occur in vivo and provide plasticity in embryo selection during early pregnancy.

Animals↗
PubMed1995

Pharmacotherapy of adult attention deficit/hyperactivity disorder: a review.

Adult attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized disorder with associated psychiatric comorbidity and impairment. Although pharmacotherapy serves an important role in treating ADHD and other concurrent psychiatric disorders in children and adolescents, the use of pharmacotherapeutics for adults with ADHD remains less established. In this report, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. A systematic review of the available literature identified 7 studies (N = 193 subjects) of psychostimulants and 10 studies of nonstimulant medications (N = 167 subjects) including antidepressants, antihypertensives, and amino acids for the treatment of ADHD in adults. The majority of double-blind investigations were with the psychostimulants, with the nonstimulant agents, generally antidepressants, studied under open conditions. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. Under controlled conditions, the aggregate literature shows that the stimulants had a clinically and statistically significant effect on reducing ADHD symptoms. Open studies on the nonserotonergic antidepressants (tricyclics, bupropion, and monoamine oxidase inhibitors) also show a moderate anti-ADHD effect. The literature appears to support the use of robust doses of both stimulants and antidepressants for ADHD in adults. Further controlled studies applying stringent diagnostic criteria and outcome methodology are necessary to define the range of pharmacotherapeutic options for adults with ADHD.

Adult↗
PubMed1997

Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy.

BACKGROUND: In the Acute Infarction Ramipril Efficacy (AIRE) Study, the effect of angiotensin-converting-enzyme (ACE) inhibition on the survival of patients with clinical heart failure after acute myocardial infarction (AMI), was assessed. At an average follow-up time of 15 months after randomisation, all-cause mortality was reduced from 22.6% (placebo group) to 16.9% (ramipril group) representing an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Our aim in this study was to assess the long-term (3 years after the AIRE Study closed) magnitude, duration, and reliability of the survival benefits observed after treatment with ramipril (target dose 5 mg twice a day) when compared with placebo. METHODS: We investigated the mortality status of all 603 patients recruited from the 30 UK centres involved in the AIRE Study. Through government records we were able to confirm the death or survival of all 603 patients exactly 3 years after the close of the AIRE Study. Follow-up was for a minimum of 42 months and a mean of 59 months. The average duration of treatment with masked trial medication was 13.4 months for placebo and 12.4 months for ramipril. FINDINGS: By 0000 h March 1, 1996, death from all causes had occurred in 117 (38.9%) of 301 patients randomly assigned placebo and 83 (27.5%) of 302 patients randomly assigned ramipril, representing a relative risk reduction of 36% (95% CI 15-52%; p = 0.002) and an absolute reduction in mortality of 11.4% (114 additional 5-year survivors per 1000 patients treated for an average of 12.4 months). INTERPRETATION: Our data provide robust evidence that administration of ramipril to patients with clinically defined heart failure after AMI results in a survival benefit that is not only large in magnitude, but also sustained over many years.

Aged↗
PubMed2000

Olanzapine versus risperidone. A prospective comparison of clinical and economic outcomes in schizophrenia.

OBJECTIVE: To compare the clinical and economic outcomes associated with olanzapine and risperidone treatment for schizophrenia. DESIGN AND SETTING: An international, multicentre, double-blind, prospective study. To facilitate economic comparisons, our sample was restricted to patients enrolled in US sites. 150 patients with a Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder were randomised to therapy with either olanzapine 10 to 20 mg/day (n = 75) or risperidone 4 to 12 mg/day (n = 75) for a maximum of 28 weeks. In addition to tolerability and efficacy assessments, use of health services was assessed at baseline and prospectively, at 8-week intervals and at study completion. Clinically important response, defined as a 40% improvement in the Positive and Negative Syndrome Scale total score, maintenance of response and rates of treatment-emergent extrapyramidal symptoms were compared between groups. Direct medical costs were estimated by assigning standardised prices to resource units. Median total, inpatient/outpatient service and medication acquisition costs were compared between treatment groups. MAIN OUTCOME MEASURES AND RESULTS: The mean modal dosages for the olanzapine and risperidone treatment groups were 17.7 +/- 3.4 mg/day and 7.9 +/- 3.2 mg/day, respectively. Olanzapine-treated patients were more likely to maintain response compared with risperidone-treated patients (p = 0.048). In addition, a smaller proportion of olanzapine-treated patients required anticholinergic therapy compared with risperidone-treated patients (25.3 vs 45.3%; p = 0.016). Total per patient medical costs over the study interval were $US2843 (1997 values) [36%] lower in the olanzapine treatment group than in the risperidone treatment group (p = 0.342). Medication costs were significantly higher for olanzapine-treated patients ($US2513 vs $US1581; p < 0.001), but this difference was offset by a reduction of $US3774 (52%) in inpatient/outpatient service costs for olanzapine-treated patients in comparison with risperidone-treated patients ($US3516 vs $US7291, p = 0.083). Median cost findings were consistent with results observed using other robust measures of central tendency and provide conservative estimates of potential savings that may be obtained from olanzapine therapy. CONCLUSIONS: In this study, olanzapine-treated patients experienced clinical improvements that translated into savings in costs of care for both inpatient and outpatient services. These savings offset the difference in medication acquisition cost between olanzapine and risperidone.

Adult↗
PubMed2006

Capillary zone electrophoresis determination of carbohydrate-deficient transferrin using the new CEofix reagents under high-resolution conditions.

Capillary zone electrophoresis (CZE) with a dynamic double coating based on the new CEofix reagents is shown to provide high-resolution separations of serum transferrin (Tf) isoforms, a prerequisite for the monitoring of unusual and complex Tf patterns, including those seen with genetic variants and disorders of glycosylation. A 50 microm I.D. fused-silica capillary of 60 cm total length, an applied voltage of 20 kV and a capillary temperature of 30 degrees C results in 15 min CZE runs of high assay precision and thus provides a robust approach for the determination of carbohydrate-deficient transferrin (CDT, sum of asialo-Tf and disialo-Tf in relation to total Tf) in human serum. Except for selected samples of patients with severe liver diseases and sera with high levels of paraproteins, interference-free Tf patterns are detected. Compared with the use of the previous CEofix reagents for CDT under the same instrumental conditions, the resolution between disialo-Tf and trisialo-Tf is significantly higher (1.7 versus 1.4). The CDT levels of reference and patient sera are comparable, suggesting that the new assay can be applied for screening and confirmation analyses. The high-resolution CZE assay represents an attractive alternative to HPLC and can be regarded as a candidate of a reference method for CDT.

Electrophoresis, Capillary↗
PubMed2006

siRNA targeting vaccinia virus double-stranded RNA binding protein [E3L] exerts potent antiviral effects.

The Vaccinia virus gene, E3L, encodes a double-stranded RNA [dsRNA]-binding protein. We hypothesized that, owing to the critical nature of dsRNA in triggering host innate antiviral responses, E3L-specific small-interfering RNAs [siRNAs] should be effective antiviral agents against pox viruses, for which Vaccinia virus is an appropriate surrogate. In this study, we have utilized two human cell types, namely, HeLa and 293T, one which responds to interferon [IFN]-beta and the other produces and responds to IFN-beta, respectively. The antiviral effects were equally robust in HeLa and 293T cells. However, in the case of 293T cells, several distinct features were observed, when IFN-beta is activated in these cells. Vaccinia virus replication was inhibited by 97% and 98% as compared to control infection in HeLa and 293T cells transfected with E3L-specific siRNAs, respectively. These studies demonstrate the utility of E3L-specific siRNAs as potent antiviral agents for small pox and related pox viruses.

Antiviral Agents↗
PubMed2000

The AMPAR subunit GluR2: still front and center-stage.

Abnormal influx of Ca(2+) through AMPA-type glutamate receptors (AMPARs) is thought to contribute to the neuronal death associated with a number of brain disorders. AMPARs exist as both Ca(2+)-impermeable and Ca(2+)-permeable channels. AMPARs are encoded by four genes designated GluR1 (GluR-A) through GluR4 (GluR-D). The presence of the GluR2 subunit renders heteromeric AMPA receptor assemblies Ca(2+)-impermeable. Molecular diversity of AMPARs under physiological and pathological conditions is generated by differential spatio-temporal patterns of GluR expression, by alternative RNA splicing and editing and by targeting and trafficking of receptor subunits at dendritic spines. The GluR2 gene is under transcriptional control by the RE1 element specific transcription factor, a gene silencing factor which renders it neuron-specific. GluR2 transcripts are edited by ADAR2 (double-stranded RNA-specific editase 1). AMPAR targeting and trafficking to spines are regulated by synaptic activity and are critical to synaptic plasticity. Recent studies involving animal models of transient forebrain ischemia and epilepsy show that GluR2 mRNA and GluR2 subunit expression are downregulated in vulnerable neurons prior to cell death. Ca(2+) imaging and electrical recording from individual pyramidal neurons in hippocampal slices reveal changes in AMPAR functional properties after ischemia. In slices from post-ischemia animals, CA1 neurons with robust action potentials exhibit greatly enhanced AMPA-elicited rises in intracellular Ca(2+). Excitatory postsynaptic currents in post-ischemic CA1 exhibit an enhanced Ca(2+)-dependent component that appears to be mediated by Ca(2+)-permeable AMPARs. These studies provide evidence for Ca(2+) influx through AMPARs in neurons destined to die. To examine whether acute GluR2 downregulation, even in the absence of a neurological insult, can induce neuronal death, we performed knockdown experiments in rats and gerbils with antisense oligonucleotides targeted to GluR2 mRNA. GluR2 antisense oligonucleotide induced neuronal cell death of pyramidal neurons and enhanced pathogenicity of brief ischemic episodes. These observations provide evidence for Ca(2+) influx through AMPARs in neurons destined to die and implicate Ca(2+)-permeable AMPARs in the pathogenesis of ischemia-induced neuronal death.

Animals↗
PubMed2004

Myosin V processivity: multiple kinetic pathways for head-to-head coordination.

Myosin V, a double-headed molecular motor, transports organelles within cells by walking processively along actin, a process that requires coordination between the heads. To understand the mechanism underlying this coordination, processive runs of single myosin V molecules were perturbed by varying nucleotide content. Contrary to current views, our results show that the two heads of a myosin V molecule communicate, not through any one mechanism but through an elaborate system of cooperative mechanisms involving multiple kinetic pathways. These mechanisms introduce redundancy and safeguards that ensure robust processivity under differing physiologic demands.

Adenosine Diphosphate↗
PubMed2001

Spectral imaging of multi-color chromogenic dyes in pathological specimens.

We have investigated the use of spectral imaging for multi-color analysis of permanent cytochemical dyes and enzyme precipitates on cytopathological specimens. Spectral imaging is based on Fourier-transform spectroscopy and digital imaging. A pixel-by-pixel spectrum-based color classification is presented of single-, double-, and triple-color in situ hybridization for centromeric probes in T24 bladder cancer cells, and immunocytochemical staining of nuclear antigens Ki-67 and TP53 in paraffin-embedded cervical brush material (AgarCyto). The results demonstrate that spectral imaging unambiguously identifies three chromogenic dyes in a single bright-field microscopic specimen. Serial microscopic fields from the same specimen can be analyzed using a spectral reference library. We conclude that spectral imaging of multi-color chromogenic dyes is a reliable and robust method for pixel color recognition and classification. Our data further indicate that the use of spectral imaging (a) may increase the number of parameters studied simultaneously in pathological diagnosis, (b) may provide quantitative data (such as positive labeling indices) more accurately, and (c) may solve segmentation problems currently faced in automated screening of cell- and tissue specimens.

Carcinoma, Transitional Cell↗
PubMed2004

Mie-scattering calculation.

The new Mie-scattering calculation is a robust and efficient algorithm used to compute light scattering from spheres. It calculates the ratio between Riccati-Bessel functions instead of the complicated logarithmic derivative. The Kapteyn inequality is used to estimate the number of significant digits of the calculated Riccati-Bessel functions and their ratio. This new algorithm is stable and accurate for both large and small particles. The implemented C++ code yields the same accurate results for both small and large particles compared with Wiscombe's MIEV0 code in double precision. Suggestions are provided for the porting of the MIEV0 code.

Journal Article↗
PubMed2000

Development of a novel, rapid integrated Cryptosporidium parvum detection assay.

The aim of this study was to develop a reverse transcription-PCR assay and lateral flow detection protocol for specific identification of Cryptosporidium parvum. The method which we developed is sensitive and specific and has a low limit of detection. In our protocol a solid phase material, the Xtra Bind Capture System, was used for extraction and purification of double-stranded RNA (dsRNA) specific for C. parvum. The Xtra Bind Capture System interfaced with pellets concentrated from water samples collected with previously developed filtration devices. The pellets were resuspended in reagent water (final volume, 0.5 ml), and an equal amount of rupture buffer and the Xtra Bind Capture System was added to the resuspended pellet mixture. The dsRNA target sequences in a 0. 5-ml portion were captured by the solid phase material via hybridization. The debris and potential inhibitors were removed by washing the Xtra Bind material several times with buffer. The Xtra Bind material with its bound dsRNA was added directly to an amplification reaction mixture, and the target was amplified without elution from the Xtra Bind material. A PCR was performed in the presence of the Xtra Bind Capture System, which resulted in robust amplification of the target. The detection system which we used was adapted from lateral flow chromatography methods typically used for antigen-antibody reactions. The result was a colored line that was visible if the organism was present. When this method was used, we were able to reproducibly and correctly identify 10 oocysts added to 0.5 ml of reagent water. When the protocol was evaluated with a small set of environmental samples, the level of detection was as low as 1 oocyst/liter. The total time from resuspension of the pellet to detection was about 3 h, which is considerably less than the 5 h required for immunomagnetic separation followed by an indirect immunofluorescence assay and microscopy.

Animals↗
PubMed1991

Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.

In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Flow-through optical fiber sensor for automatic sulfide determination in waters by multisyringe flow injection analysis using solid-phase reflectometry.

A software-controlled flow-through optical fiber diffuse reflectance sensor capitalized on the implementation of disk-based solid-phase pre-concentration schemes in a multisyringe flow injection analysis (MSFIA) set-up is proposed for the trace determination of sulfide in environmental waters and wastewaters. The fully automated flowing methodology is based on Fischer's coupling reaction of sulfide with N,N-dimethyl-p-phenylenediamine (DMPD) in the presence of Fe(iii) as oxidizing reagent in a 0.5 M HCl medium. The on-line generated methylene blue dye is subsequently delivered downstream to a dedicated optode cell furnished with an octadecyl-chemically modified (C(18)) disk, while continuously recording the diffuse reflectance spectrum of the pre-concentrated compound. A double regeneration protocol is finally executed to warrant minimum background noise and negligible baseline. Under the optimized chemical and hydrodynamic conditions, the optosensing MSFIA method features coefficients of variation better than 0.7%(n= 10) at 50 microg l(-1) concentration, a linear working range of 20-200 microg l(-1) sulfide, a 3sigma(blank) detection limit of 2.9 microg l(-1) sulfide and an injection throughput of 8 h(-1) for a pre-concentration sample volume of 2.9 ml. The interfacing of the robust and versatile multisyringe flow injection-based optode with a plug-in spectrophotometer furnished with a light emitting diode assures the miniaturization of the overall flow analyzer, which is, thus, readily adaptable to real-time monitoring schemes. The potential of the multisyringe flow method was assessed via the determination of sulfide traces in water samples of different complexity (namely, freshwater, seawater and wastewater).

Fiber Optic Technology↗
PubMed2001

Developing organizational learning in the NHS.

Learning has been identified as a central concern for a modernized NHS. Continuing professional development has an important role to play in improving learning but there is also a need to pay more attention to collective (organizational) learning. Such learning is concerned with the way organizations build and organize knowledge. Recent emphasis within the NHS has been on the codification of individual and collective knowledge - for example, guidelines and National Service Frameworks. This needs to be balanced by more personalized knowledge management strategies, especially when dealing with innovative services that rely on tacit knowledge to solve problems. Having robust systems for storing and communicating knowledge is only one part of the challenge. It is also important to consider how such knowledge gets used, and how routines become established within organizations that structure the way in which knowledge is deployed. In many organizations these routines favour the adaptive use of knowledge, which helps organizations to achieve incremental improvements to existing practices. However, the development of organizational learning in the NHS needs to move beyond adaptive (single loop) learning, to foster skills in generative (double loop) learning and meta-learning. Such learning leads to a redefinition of the organization's goals, norms, policies, procedures or even structures. This paper argues that moving the NHS in this direction will require attention to the cultural values and structural mechanisms that facilitate organizational learning.

Education, Medical↗
PubMed1998

Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change.

Experimental investigations of eukaryotic enhancers suggest that multiple binding sites and trans-acting regulatory factors are often required for wild-type enhancer function. Genetic analysis of the stripe 2 enhancer of even-skipped (eve), an important developmental gene in Drosophila, provides support for this view. Given the importance of even-skipped expression in early Drosophila development, it might be predicted that many structural features of the stripe 2 enhancer will be evolutionarily conserved, including the DNA sequences of protein binding sites and the spacing between them. To test this hypothesis, we compared sequences of the stripe 2 enhancer between four species of Drosophila: D. melanogaster, D. yakuba, D. erecta and D. pseudoobscura. Our analysis revealed a large number of nucleotide substitutions in regulatory protein binding sites for bicoid, hunchback, Kruppel and giant, as well as a systematic change in the size of the enhancer. Some of the binding sites in D. melanogaster are either absent or modified in other species. One functionally important bicoid-binding site in D. melanogaster appears to be recently evolved. We, therefore, investigated possible functional consequences of sequence differences among these stripe 2 enhancers by P-element-mediated transformation. This analysis revealed that the eve stripe 2 enhancer from each of the four species drove reporter gene expression at the identical time and location in D. melanogaster embryos. Double staining of native eve protein and transgene mRNA in early embryos showed that the reporter gene mimicked native eve expression and, in every case, produced sharply defined stripes at the blastoderm stage that were coincident with eve stripe 2 protein. We argue that stripe 2 eve expression in Drosophila evolution can be viewed as being under constant stabilizing selection with respect to the location of the anterior and posterior borders of the stripe. We further hypothesize that the stripe 2 enhancer is functionally robust, so that its evolution may be governed by the fixation of both slightly deleterious and adaptive mutations in regulatory protein binding sites as well as in the spacing between binding sites. This view allows for a slow but continual turnover of functionally important changes in the stripe 2 enhancer.

Animals↗