Biomedical subjects

G Fontanesi

Publications and source records attributed to G Fontanesi.

At least 19 recordsLinked to original sources

PubMed2000

Postnatal development of somatostatin 2A (sst2A) receptors expression in the rabbit retina.

In the retina, somatostatin (SRIF) acts as a neuromodulator by interacting with specific SRIF subtype (sst) receptors. Aim of this investigation was to determine the cellular localization of the sst2A receptor isoform in the postnatal rabbit retina. Receptor immunoreactivity was localized using the antiserum K-230, directed to the C-terminus of the human sst2A receptor. In the postnatal rabbit retina, sst2A receptors were abundantly expressed without significant regional differences. They were localized predominantly to rod bipolar cells, identified with a protein kinase C (PKC) antibody, to amacrine cells, some of which also containing tyrosine hydroxylase (TH), and to presumed rare horizontal cells. Quantitative analysis showed that sst2A-immunoreactive (-IR) bipolar and amacrine cells reached their maximum density and absolute number at the time of eye opening, when the expression pattern of sst2A receptors was similar to that in adult retinas. In the adult retina, 68% of the PKC-IR rod bipolars and 34% of the TH-IR amacrine cells were observed to also express sst2A receptors. The appearance of sst2A receptor immunolabeling prior to eye opening and the developmental profile of sst2A receptor expression are compatible with a role of SRIF in the maturation of retinal circuitries. The partial expression of sst2A receptors in PKC-IR rod bipolar cells and in TH-IR amacrine cells may suggest some type of heterogeneity within these cell populations.

Animals↗

PubMed2000

Expression of somatostatin subtype 1 receptor in the rabbit retina.

PURPOSE: To detect mRNAs for somatostatin (somatotropin release-inhibiting factor [SRIF]) receptor subtypes 1 to 5 (sst(1) through sst(5)) in rabbit retinas by reverse transcription-polymerase chain reaction (RT-PCR) and to investigate the distribution of sst(1) by single- and double-label immunocytochemistry. METHODS: Semiquantitative RT-PCR using sst-specific primers from mouse sequences was performed. sst(1) was localized using a polyclonal antiserum directed to human sst(1) in cryostat sections of retinas from either normal or optic nerve-transected animals. Immunolabeled cell sizes and densities were measured in wholemounted retinas using computer-assisted image analysis. Double-label immunofluorescence was performed using the sst(1) antiserum in conjunction with monoclonal antibodies directed to SRIF, tyrosine hydroxylase (TH), parvalbumin (PV), or gamma-aminobutyric acid (GABA). RESULTS: With RT-PCR it was found that all five sst mRNAs were expressed in the rabbit retina, with highest levels of sst(1) mRNA. sst(1) immunolabeling was localized to amacrine cells in the proximal inner nuclear layer (INL) of all retinal regions and to displaced amacrine cells in the ganglion cell layer (GCL) of the ventral retina. Some large sst(1)-immunoreactive (IR) somata were also present in the GCL. They were not observed after optic nerve transection. Double-label immunofluorescence showed sst(1) expression by all TH-IR amacrine cells and by other amacrine cells that were neither PV-IR nor GABA-IR. In addition, sst(1) was expressed by all SRIF-containing displaced amacrine cells. CONCLUSIONS: All five sst mRNAs are expressed in the rabbit retina. The localization of sst(1) suggests that it may mediate SRIF actions onto amacrine (including dopaminergic) and sparse ganglion cells. sst(1) expression in SRIF-IR cells suggests that this receptor may also act as an autoreceptor.

Animals↗

PubMed1999

Effects of metal ions on white blood cells of patients with failed total joint arthroplasties.

In this study twenty-two patients who had revision surgery for aseptic loosening of joint prostheses were examined. The concentration in serum of soluble products of corrosion from the implant, that is, chromium (Cr), cobalt (Co), and nickel (Ni) ions, and the number of white blood cells (leucocytes, myeloid cells, lymphocyte subpopulations) were measured. Twenty patients with no implants were used as controls. The patients who had revision surgery showed normal Ni concentration whereas by statistical analysis that same patient group was shown to have serum Cr and Co levels significantly higher than those of the control. By flow cytometry, a significant decrease of leucocytes, myeloid cells, lymphocytes, and CD16 populations as found in patients versus controls whereas CD3, CD4, CD8, and CD20 positive cells were decreased, but not significantly. In the arthroplasty patients the Cr concentrations were inversely correlated with some of the immunologic parameters while no significant correlation was found between Co levels and decreased lymphocyte subpopulations. Only in revision surgery patients with high Cr concentrations did we find a significant decrease of lymphocytes, namely of CD4 and CD16 positive cells; revision surgery patients with normal Cr concentrations did not show a significant decrease of lymphocyte subpopulations. These data suggest that the presence of metal ions, especially chromium, released from prosthesis components could be associated with changes of lymphocyte subpopulations in patients with loosening of joint prostheses.

Adult↗

PubMed1998

Chronic exposure to either somatostatin (SS) or octreotide, a long-lasting SS analogue, affects SS expression in the postnatal visual cortex of the rat.

The peptide somatostatin (SS) is widely distributed in the mammalian brain where it modulates neuronal activity through interactions with specific membrane-bound receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5) and their selective agonists were developed on the basis of their binding specificity. SS and ssts are transiently expressed in the developing brain, suggesting a functional role of somatostatinergic systems in neuronal maturation. In the present study, we investigated the effects of chronic exposure to either the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual cortex of the rat. SS-ir maturation was investigated both by an evaluation of the number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the levels of SS in the postnatal visual cortex. In the visual cortex of normal rats, the number of SS-positive cells markedly increased during the second postnatal week and then significantly decreased until the adult value was reached at the third week. Early and repeated intracerebroventricular (i.c.v.) injections of either SS-14 or octreotide prevented the increase in the number of SS-positive cells, with adult values reached at the end of the first postnatal week. Similarly, administration of either SS-14 or octreotide significantly decreased the SS content of the visual cortex, measured at the end of the second postnatal week. These results show that high local concentrations of either SS-14 or octreotide interfere with SS expression in developing cortical neurons in a restricted postnatal period.

Aging↗

PubMed1997

Transient somatostatin-immunoreactive ganglion cells in the developing rat retina.

The peptide somatostatin (SRIF) is likely to play important roles in neuronal differentiation and maturation. In the mammalian retina, it is reported to be expressed by populations of amacrine and/or displaced amacrine cells and, in some species, by some ganglion cells. Previous studies have shown that in the rat retina the maturation of somatostatinergic systems encompasses late prenatal and early postnatal periods, suggesting a role of SRIF in maturative events of the retina. SRIF-expressing ganglion cells have not been reported in the rat retina at any developmental age. In the present study, we re-evaluated the postnatal development of SRIF-containing neurons of the rat retina focusing on the analysis of SRIF-containing cells in the ganglion cell layer (GCL), to test the possibility that SRIF is expressed by some ganglion cells during development. To this aim we combined immunocytochemical staining of SRIF-positive neurons with retrograde tracing of ganglion cell bodies through Fluoro-Gold injections into the superior colliculus. Double-labelling experiments revealed the presence of SRIF-containing ganglion cells at postnatal day (PND) 10. They accounted for 14% of the total SRIF-containing cells in the GCL. Such double-labelled cells were not observed either before (PND 7) or after (PND 15 and PND 45) this period. This transient expression of SRIF in retinal ganglion cells suggests that SRIF may be a factor regulating the maturation of retinocollicular projections in a restricted period of postnatal development.

Aging↗

PubMed1997

The neuroethology of cognitive maps: contributions from research on the hippocampus and homing pigeon navigation.

The rich ethological tradition that characterizes the homing behavior of pigeons offers an excellent opportunity to examine the importance of the hippocampal formation for the regulation of spatial cognitive mechanisms. The present review summarizes both anatomical and behavioral data obtained in researches on the pigeon hippocampal formation that have been performed over the last 12 years. Pathway connection studies and investigations on the neurochemical organization of the avian hippocampal formation show that this structure shares many similarities with the mammalian hippocampus and provide the basis for structural as well as functional homology. The initial research on the role of the hippocampal formation in the homing behavior showed that this brain structure is likely to be involved in phenomena of spatial cognition. Therefore, the homing behavior of pigeons has been extensively used as an experimental model to investigate the role of the hippocampal formation in spatial cognition related to a naturally occurring behavior. These studies have revealed that the hippocampal formation plays a fundamental role in the learning of a navigational map based on atmospheric odors, but it doesn't seem to be involved in the operation of such a map. In contrast, both the learning and the operation of a navigational map based on the recognition of familiar landmarks require a functional hippocampal formation. Further investigations indicated that these functions of the hippocampal formation are mediated by its involvement in the use of the sun compass, and suggested that the hippocampal formation plays a fundamental role in a cognitive process in which the sun compass is specifically used to learn about the location of stimuli in space. The studies reviewed in the present paper have provided a considerable amount of experimental data both on the anatomical/neurochemical organization of the avian hippocampal formation and on the role played by this brain structure in spatial cognition. The future development of these researches will need to consider the contribution to hippocampal function of specific transmitter systems that are involved in hippocampal circuitry. In particular, the afferent cholinergic system and some of the peptidergic systems intrinsic to the hippocampal formation deserve particular attention in view of their possible involvement in the acquisition and/or operation of spatial cognitive abilities by homing pigeons.

Animals↗

PubMed1994

Neuroactive substances in the developing dorsomedial telencephalon of the pigeon (Columba livia): differential distribution and time course of maturation.

The avian hippocampal formation has previously been shown to contain many of the same neurotransmitters and related enzymes that are found in mammals. In order to determine whether the relatively delayed development of the mammalian hippocampus is typical of other vertebrates, we investigated the maturation of a variety of neuroactive substances in the hippocampal formation of the homing pigeon. The distribution of two transmitter-related enzymes, choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), the neurotransmitter GABA, and four neuropeptides (substance P, enkephalin, neuropeptide Y, and somatostatin) was studied by immunohistochemistry in the developing hippocampal complex. The pattern and/or the time course of changes in the distribution of immunoreactivity varied among the different neuroactive substances examined. Immunoreactivity to ChAT and TH was found exclusively in fibers and terminal-like processes, whereas GABA and peptide immunoreactivity was seen in cells and neuropil. Quantitative differences in the density, number, and size of stained cells were assessed by a computer-assisted image analyzer. For the majority of the substances, developmental patterns in the distribution of immunoreactivity differ between the hippocampus proper and the area parahippocampalis, the two major areas that together make up the avian hippocampal complex. The adult pattern of immunoreactivity was generally attained by 3 weeks after hatching. For many of the neuroactive substances found in cell bodies, there was a gradual decrease in the density of immunoreactive cells with a concomitant increase in the density of immunoreactive neuropil. The actual number of stained cells usually increased to a peak at 9 days posthatching and then declined until 3 weeks posthatching, when the adult value was reached. These results are discussed in relation to the advantages that the pigeon hippocampal complex may provide in the study of developmental processes. Parallels with the distribution of the same neuroactive substances in the mammalian hippocampus are used to suggest possible functional similarities between the avian and mammalian hippocampal regions.

Animals↗

PubMed1993

[A comparative evaluation of the remission from acute lumbar-sciatic pain following treatment with meclofenamic acid and naproxen].

This study was performed to assess the analgesic effect and the onset of action of meclofenamic acid compared with naproxene in patients affected by acute lumbar-sciatic pain. Thirty patients of both sexes were randomly allocated to 2 groups of 15 patients each; the first group was treated with meclofenamic acid (200 mg b.i.d.) and the second with naproxene (500 mg b.i.d.). Both drugs were administered as suppositories for a week. The intensity of pain, both at rest and after movement, was assessed by means of analogic scales at basal time and 15, 30, 60, 180, 360 minutes, 4 and 8 days after the first administration. Both types of pain were significantly decreased with respect to basal values in meclofenamic acid group (P < 0.01), 60 minutes after onset of treatment, while in the naproxene group the effect was later. Moreover the analgesic effect was significantly greater in the meclofenamic acid group with respect to the naproxene group, after 15 minutes for pain at rest (P < 0.05) and after 30 minutes for pain after movement (P < 0.02). Similarly, after 4 and 8 days, both types of pain improved to a larger extent in the meclofenamic acid group with respect to the naproxene group (P < 0.05 after four days and P < 0.01 after eight days). This study has shown that meclofenamic acid has greater efficacy and faster analgesic effect than naproxene. Meclofenamic acid has proved to be a drug of choice in the treatment of slight to moderate musculo-skeletal pain syndromes.

Acute Disease↗

PubMed1992

Distribution of neuropeptide Y, substance P, and choline acetyltransferase in the developing visual system of the pigeon and effects of unilateral retina removal.

The distribution of three neuroactive substances, neuropeptide Y, substance P, and choline acetyltransferase, was studied by immunocytochemical methods in central visual regions of adult, developing, and ablated pigeon brains. In normal adult brains, neuropeptide Y-positive cells and processes were present in the nucleus pretectalis, the nucleus of the basal optic root, the nucleus of the marginal optic tract, and the visual Wulst. Substance P-positive cells and processes were found in the optic tectum and in the visual Wulst. Stained fibers and terminal-like processes, but no cells, were also observed in several visual thalamic nuclei. Choline acetyltransferase-positive cells and processes were located in the optic tectum, visual Wulst, the nucleus isthmo opticus, nucleus isthmi and certain visual thalamic nuclei. Cholinergic fibers and processes, but no cells, were present in the nucleus principalis precommissuralis, the supraoptic decussation, and the nucleus lentiformis mesencephali, pars magnocellularis. In the course of development, the distribution of immunoreactivity for all three substances was found to vary. These changes often involved either progressive increases or decreases in the density of labeled cells, neuropil and/or terminal-like profiles. Experiments with retina ablated pigeons clearly demonstrated that changes in the normal pattern of immunoreactivity distribution only occurred if the retina was removed immediately after hatching, i.e., before retinofugal connections have been established. The adult pattern of immunoreactivity for all three substances appears to be reached at about the same time that the anatomical and functional maturation of the pigeon visual system is completed. The present results suggest that this temporal correlation reflects the important role that retinal afferents play in the development of these putative peptidergic and cholinergic systems.

Aging↗

PubMed1992

Wulst efferents in the little owl Athene noctua: an investigation of projections to the optic tectum.

The efferent projections from the Wulst were studied in the little owl, Athene noctua, using anterograde migration of wheat-germ-agglutinin conjugated horseradish peroxidase (WGA-HRP). Wulst projections were distributed to telencephalic, diencephalic and mesencephalic targets in a general pattern similar to that previously described in other avian species. Our results on the organization of the Wulst-optic tectum pathway in the little owl reveal well defined and laminarly arranged terminal projections into the superficial tectal layers, with a distribution suggestive of topographical relationships between neurons of origin in the Wulst and termination fields in the optic tectum. In contrast to lateral-eyed birds, the little owl possesses conspicuous contralateral projections to the optic tectum. Ipsilateral and contralateral efferents are restricted to different tectal regions, i.e. ipsilateral projections to the caudo-dorsal and contralateral projections to the rostro-ventral optic tectum. In addition, the anterior and posterior Wulst differentially contribute to the ipsilateral and contralateral projections to the optic tectum. This differential organization of Wulst efferents, as well as the presence of substantial contralateral projections, might be related to the high degree of binocular overlap typical of frontal-eyed birds. At a functional level, electric potentials recorded in the optic tectum and evoked by visual stimulation showed that information from one eye can reach the ipsilateral optic tectum. After Wulst ablation, the amplitude of these potentials was significantly reduced, indicating that Wulst efferents may influence visually-evoked activity in the optic tectum.

Animals↗

PubMed1991

Intertrochanteric valgus osteotomy and sliding compression hip screw in fractures of the femoral neck.

Twenty-four patients ranging from 28 to 56 years of age with Garden grade III or IV fractures of the femoral neck are reviewed after treatment by intertrocherantic valgus osteotomy and Richards sliding compression hip screw. The rationale behind this treatment, the operative technique, and the choice of internal fixation device are all discussed. All patients were followed up after more than 2 years so that any late complications could be documented. The results were evaluated using both the Merle d'Aubigné procedure and radiographic examination: 12 (50%) were rated excellent, 5 (20.8%) good, 2 (8.4%) fair, and 5 (20.8%) poor. The unsatisfactory results are analyzed in detail, attributable to non-union in 2 cases (due to technical error), avascular necrosis in 4 cases (2 were limited and well-tolerated by the patients; 2 were early and massive and necessitated prosthetic replacement), and infection in one case. Even though valgus osteotomy and internal fixation fill a gap in the treatment of femoral neck fractures in adults by yielding good results with a conservative method, they are very demanding surgical procedures, requiring anatomical reduction, atraumatic technique, precise calculation of the valgus angle, and precise placement of the internal fixation device.

Adult↗

PubMed1991

Immediate multiple osteosynthesis in polytrauma.

Thirty polytraumatized patients underwent immediate osteosynthesis of two or more long bone fractures for a total of 82 operations (plus an additional 14 for pelvis, hand, and foot fractures). Since 1983, according to the modern and rational concepts of "all at one time treatment", open fractures as well as associated closed lesions are stabilized immediately if the patient's general condition permits. This type of procedure requires adequate facilities as well as availability of and collaboration between teams of specialists, but it is inarguably advantageous for the patient (relief of pain, drastic reduction in the rate of embolism, improvement of respiratory and circulatory function, only one anesthesia), the surgeons (operation technically easier and shorter), and the ancillary medical personnel (easier nursing, rapid functional rehabilitation). The methods of osteosynthesis should be carefully selected in order to guarantee stability, rapid application, and low aggressiveness. The use of plates and screws is limited, while external fixation is employed frequently. Interlocked intramedullary nailing is adopted with increasing frequency. Review of cases treated by this method shows considerable improvement in terms of healing, functional recovery, and resumption of social and occupational activity.

Adult↗

PubMed1991

Retention of the posterior cruciate ligament in total knee arthroplasty.

The importance of the preservation of the posterior cruciate ligament in total knee arthroplasty is analyzed from a biomechanical, clinical, and functional standpoint. Using clinical and radiographic criteria, the authors assess posterior cruciate ligament validity in a selected group of 31 of 45 total knee arthroplasties (PCA prosthesis) reviewed at least 18 months after the operation. Sixty-eight percent of the replaced knees, which were divided into two groups on the basis of preoperative deformity, had a functional posterior cruciate ligament. In view of these results the authors are satisfied with the prosthetic model they adopted, which was designed not only to preserve the posterior cruciate ligament, but also, by virtue of its special shape, to compensate in the event of ligament insufficiency.

Activities of Daily Living↗

PubMed1990

Binocularity in the little owl, Athene noctua. I. Anatomical investigation of the thalamo-Wulst pathway.

The efferent projections from the visual thalamus to the Wulst were studied in the little owl, Athene noctua. Cells of origin were identified by retrograde labeling after injections of wheat-germ-agglutinin-conjugated horseradish peroxidase into the Wulst. The labeled-cell distribution was correlated with the distribution of anterogradely labeled retinal terminals as revealed by intraocular injections of horseradish peroxidase. The results demonstrated a bilateral thalamofugal visual pathway ascending from the nucleus dorsolateralis anterior thalami (DLA). Projections from the visual thalamus to the Wulst showed a specific and orderly pattern, and retrogradely labeled cells of DLA were distributed equally, in a complementary fashion, on both sides of the brain, with a small region of overlap. Retinal termination fields in DLA largely overlapped relay neurons projecting to either Wulst, although the overlap was not complete. Despite differences in the organization of avian and mammalian visual pathways, which reflect their separate evolutionary origins, similarities between the DLA in the little owl and the lateral geniculate nucleus in mammals suggest that, during evolution similar selective pressures for binocularity led to a similar morphological organization.

Animals↗

PubMed1990

Binocularity in the little owl, Athene noctua. II. Properties of visually evoked potentials from the Wulst in response to monocular and binocular stimulation with sine wave gratings.

Visually evoked potentials (VEPs) have been recorded from the Wulst surface of the little owl, Athene noctua, in response to counterphase-reversal of sinusoidal gratings with different contrast, spatial frequency and mean luminance, presented either monocularly or binocularly. Monocular full-field stimuli presented to either eye evoked VEPs of similar amplitude, waveform and latency. Under binocular viewing, VEPs approximately doubled in amplitude without waveform changes. VEPs with similar characteristics could be obtained in response to stimulation of the contralateral, but not ipsilateral, hemifield. These results suggest that a 50% recrossing occurs in thalamic efferents and that different ipsilateral and contralateral regions converge onto the same Wulst sites. The VEP amplitude progressively decreased with increase of the spatial frequency beyond 2 cycles/degree, and the high spatial frequency cut-off (VEP acuity) was under binocular viewing (8 cycles/degree) higher than under monocular (5 cycles/degree) viewing (200 cd/m2, 45% contrast). The VEP acuity increased with increase in the contrast and decreased with reduction of the mean luminance. The binocular gain in both VEP amplitude and VEP acuity was largest at the lowest luminance levels. Binocular VEP summation occurred in the medium-high contrast range. With decreased contrast, both monocular and binocular VEPs progressively decreased in amplitude and tended to the same contrast threshold. The VEP contrast threshold depended on the spatial frequency (0.6-1.8% in the range 0.12-2 cycles/degree). Binocular VEPs often showed facilitatory interaction (binocular/monocular amplitude ratio greater than 2), but the binocular VEP amplitude did not change either by changing the stimulus orientation (horizontal vs. vertical gratings) or by inducing different retinal disparities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Cemented arthroprosthesis in femoral neck fractures.

Primary total hip replacement in femoral neck fractures is still controversial. This report presents the findings of a study of 42 femoral neck fractures treated with cemented arthroprosthesis with an average follow-up of five years. The patients were divided into two groups according to the type of prosthesis, the reaming and cementing techniques, and the type of operating room. Each group had positive results in about 80% of the cases, testifying to the fact that arthroprosthesis is a valid method of treatment provided that the following procedures are scrupulously carried out: the preparation of the patient, the choice and implantation of the prosthesis, and the functional and psychological rehabilitation of the patient.

Aged↗

PubMed1989

Reorganization of visual pathways following posthatching removal of one retina in pigeons.

Organization of visual pathways was studied in 2-month-old pigeons that underwent unilateral retinal removal on either the day of hatching (ERA, i.e., early retinal ablated) or the 9th day after hatching (LRA, i.e., late retinal ablated). A general size reduction of visual areas contralateral to the removed retina was found in ERA pigeons, which additionally showed an altered differentiation of thalamic visual targets as well as a different cytoarchitectonic arrangement of the superficial layers of the optic tectum. No comparable modifications were found in LRA pigeons. The retinal projections of the remaining eye were studied following intraocular injections of 3H-proline. Both in ERA and LRA pigeons, the distribution of retinofugal afferents to primary visual regions contralateral to the injected eye was similar to that of control pigeons. Anomalous ipsilateral projections from the remaining retina to primary retinorecipient regions were found in ERA pigeons only. Effects of early ablation of one retina on second-order visual connections were also studied. Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the visual Wulst contralateral to the operated eye, a smaller number of ipsilateral projecting thalamo-Wulst neurons was found as compared with control pigeons. In contrast, the contralateral thalamo-Wulst projections were increased. No changes in thalamo-Wulst projections were found following tracer injections into the opposite Wulst, i.e., ipsilateral to the operated eye. The present study demonstrates a substantial anatomical reorganization of both primary and secondary visual pathways following unilateral retinal removal immediately after hatching, when maturation of the visual system is not yet completed.

Animals↗

PubMed1989

The electroretinogram of the little owl (Athene noctua).

Electroretinographic responses (ERGs) have been recorded from the cornea of the little owl (Athene noctua) in response to single light flashes and to alternating sinusoidal gratings (pattern) at different levels of light adaptation. Both flash- and pattern-evoked ERGs show scotopic as well as photopic components. The pattern evoked ERG is spatially tuned with tuning functions which shift towards lower frequencies by reducing the mean luminance. The retinal acuity is about 6 c/deg at 2.3 log cd/m2 and decreases progressively by reducing the mean luminance. No pattern ERG can be recorded beyond -6.7 log cd/m2 at any spatial frequency. The pattern ERG amplitude decreases progressively by reducing the contrast. The extrapolated contrast threshold is about 1%. Acuity and contrast sensitivity ERG values are in the range of those obtained by operant techniques in other species with duplex retinae such as owls and cats.

Animals↗