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PubMed1999

Clinical features of Chlamydia trachomatis rectal infection by serovar among homosexually active men.

BACKGROUND AND OBJECTIVES: Because C. trachomatis serovars correlate with the clinical manifestations of cervical infection, we undertook this study to determine whether clinical, behavioral, and laboratory findings correlate with C. trachomatis serovars isolated from rectal infections. GOAL OF THIS STUDY: To correlate C. trachomatis serovar with signs and symptoms of rectal infection. STUDY DESIGN: A cross-sectional study of 454 men with rectal C. trachomatis infection attending an urban sexually transmitted disease (STD) clinic was undertaken. Isolates were thawed, passaged to high titer, and typed using a panel of monoclonal antibodies. Compared to men infected with B complex isolates (164), men with C complex isolates (55) were less likely to report symptoms (OR: 0.4; 95% CI: 0.1-0.8), or to have erythema, bleeding, or mucopus (OR: 0.3; 95% CI: 0.1-0.8). Among men with inclusion counts of more than 100, those infected with FG group versus B complex isolates were more likely to present with mucopus (OR: 10.5; 95% CI: 1.2-95.5), more than 15 polymorphonuclear leukocytes (OR: 19.2; 95% CI: 1.7-219.8), and proctitis (OR: 4.2; 95% CI: 1.1-16.7). CONCLUSION: Signs and symptoms of rectal infection correlate with the serovar of C. trachomatis isolates.

Adult↗
PubMed2000

HIV-1 infection-associated risk factors among sexually transmitted disease patients in Athens, Greece: 1990 to 1996.

OBJECTIVE: To determine trends in HIV seroprevalence and related risk factors among patients with sexually transmitted diseases (STDs) and to report the respective epidemiologic history characteristics. METHODS: A cross-sectional seroepidemiologic study conducted from 1990 to 1996 among 5,669 symptomatic STD cases was carried out. RESULTS: The overall HIV test acceptance was 98.9%, and 1.2% patients (n = 66) were seropositive. Highest rates were detected among those who were born or resided in Sub-Saharan Africa. Seropositivity fluctuates significantly by age, and is excessive in persons 45 years and older (2.6%). A significant decreasing trend in STD incidence and HIV seroprevalence among patients younger than 25 years was detected. Male homosexuals and bisexuals (MSM) exhibited the highest overall rate of infection (5.8%) followed by intravenous drug users (2%). Highly promiscuous STD patients (ie, those who had more than 10 partners during the past 6 months) presented a significantly increased HIV seroprevalence when compared with patients of the same sexual orientation. STD patients infected with HIV mostly belonged to notable risk categories of AIDS (men who have sex with men, 72.7%). Awareness of serostatus was low (13.6%). In male patients, the HIV seropositivity rate was significantly higher among early syphilis and proctitis cases, whereas in females this higher rate occurred with herpes genitalis. CONCLUSIONS: Promiscuity and sexual orientation significantly influence the seroprevalence rate. Exposure to HIV remained stable despite the above declining time trends, which implies the need for additional preventive interventions targeted to the real health and illness behavior of the partner.

Adult↗
PubMed1981

Chlamydial genital infections: manifestations and management.

Infection with Chlamydia trachomatis is an important cause of nongonococcal urethritis and cervicitis, and may be the most common sexually transmitted disease in the United States. Associated complications include epididymitis, proctitis, salpingitis, bartholinitis, arthritis, perihepatitis, and endocarditis. Perinatal transmission of infection may result in neonatal inclusion conjunctivitis and/or pneumonia of infancy. Chlamydial genital infection should be suspected in a patient (male or female) who presents with a gonorrhea-like syndrome but whose laboratory studies fail to demonstrate Neisseria gonorrhoeae. Such patients, together with their sex partners, should receive antichlamydial therapy; the uncomplicated genital infections respond well to oral treatment with tetracycline, erythromycin, and sulfonamide. The most important cause of treatment failure in nongonococcal urethritis is lack of simultaneous treatment of both patient and partner.

Erythromycin↗
PubMed1998

Ongoing advances in inflammatory bowel diseases, including maintenance therapies, biologic agents, and biology of disease.

Inflammatory bowel diseases remain a significant chronic disease affecting children and adolescents. Although corticosteroids remain the standard form of therapy for many patients, an era of biological agents for therapy in inflammatory bowel diseases is upcoming with human trials using these agents now forthcoming. In addition, studies on maintenance of remission are beginning to address the selection of those patients most likely to benefit from aminosalicylate therapies, the risks of relapse from using cyclooxygenase inhibitors, the lack of benefit from lipoxygenase inhibitors, and possible future methodologies to examine the effectiveness of the immuno-suppressive agent 6-mercaptopurine. Further development of the hypothesis that new-onset disease may be different than longstanding disease can be appreciated with reports of cytokine analysis in new-onset inflammation and the high risk of progression of disease in new-onset ulcerative proctitis in children. With more reports on the role of intestinal epithelial cells in intestinal diseases, it is now clear that this cell layer is not a passive bystander with regard to the interactions between the luminal contents and immune system components found within the lamina propria; new studies suggest that novel therapeutic strategies may be possible. This review summarizes recently reported aspects of Crohn's disease and ulcerative colitis, with an emphasis on issues-pertinent for younger patients.

Anti-Inflammatory Agents↗
PubMed1997

Guidelines for the treatment of ulcerative colitis in remission.

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Preoperative concomitant hyperfractionated radiotherapy and gemcitabine for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: The purpose of this study was to determine the maximum tolerated dose of gemcitabine when it was administered concomitantly with hyperfractionated radiotherapy before surgery in patients with locally advanced rectal cancers and to investigate the midterm efficacy of such a regimen. PATIENTS AND METHODS: Thirty-seven patients with stage II-III tumors as assessed by computed tomography/echoendoscopy were enrolled. Radiotherapy consisted of 50 Gy given in two daily fractions of 1.25 Gy over 4 weeks. The starting dose of gemcitabine was 10 mg/m(2)/day (in a 30-minute i.v. perfusion) twice weekly with planned escalation steps of 5 mg/m(2)/day. Surgery was planned at 6 weeks after the end of radiotherapy. Main end-points of the study were complete pathological tumor response, the rate of clear margin resection, and actuarial locoregional control and disease-free survival. The median follow-up for all patients was 32 months (range: 10-51 months). RESULTS: At the level of 45 mg/m(2), two of four patients presented with dose-limiting rectal toxicities (severe acute proctitis requiring hospitalization in the immediate postradiotherapy period). Thus, the gemcitabine biweekly dose of 40 mg/m(2) was considered to be the maximum tolerated dose. Among the 36 patients who underwent surgery, 17 (47%) had a marked pathological response, including six patients (17%) with a microscopically complete response and 11 (30%) with only microscopically residual carcinoma of less than 1 cm. All of them had clear surgical margins. At 3 years, actuarial overall survival rate was 85%, locoregional control was 94.5%, and disease-free survival was 67%. DISCUSSION: The present study determined the recommended dose of gemcitabine to be 40 mg/m(2) when administered concurrently twice a week with 50 Gy hyperfractionated radiotherapy for the preoperative treatment of locally advanced rectal cancers. The encouraging pathological response rate and the very low locoregional recurrence rate suggest that this innovative approach merits further investigation.

Adult↗
PubMed2006

Preoperative radiotherapy alone or combined with chemotherapy followed by transanal excision for rectal adenocarcinoma.

OBJECTIVE: To evaluate the efficacy of preoperative radiotherapy (RT) and chemoradiation (CRT) followed by transanal excision (TAE) for rectal adenocarcinoma. METHODS: Thirty-two patients were treated between July 1988 and April 2004 and followed from 2 to 123 months (median, 27 months). RESULTS: The 3-year outcomes were: locoregional control, 79%; distant metastasis-free survival, 80%; cause-specific survival, 88%; and overall survival, 75%. Outcomes were better for patients with T1-T2 tumors and those who experienced a complete response to preoperative RT or CRT. Two patients (6%) had chronic RT proctitis after treatment. CONCLUSION: A select subset of patients with T2/T3 tumors will experience similar outcomes after preoperative RT or CRT and TAE compared with radical proctectomy. Reliably predictive clinicopathologic features to define this subgroup would best be elicited in the context of large prospective randomized trials, as would the optimal combination and schedule of systemic agents delivered in conjunction with preoperative RT. Patients who experience a complete response (cCR) after preoperative CRT are excellent candidates for TAE; those with less than a cCR have a less-favorable prognosis and are probably better treated with a low anterior resection or abdominal-perineal resection.

Adenocarcinoma↗
PubMed2003

Urethrorectal fistula: transanal, transsphincteric approach with locally based pedicle interposition flaps.

PURPOSE: We report preliminary experience with the transsphincteric, transanal surgical approach to correct acquired urethrorectal fistula. MATERIALS AND METHODS: Five men with an acquired urethrorectal fistula underwent surgical correction. Mean patient age was 56.6 years (range 37 to 72). The etiology was surgical (radical prostatectomy) in 3 cases, traumatic in 1 and idiopathic in 1. All 5 patients had urinary tract infection and pneumaturia, and 3 (60%) had watery stool. Conservative treatments had failed in all cases. The time from the diagnosis of urethrorectal fistula to surgery was 4 weeks to 4 years. RESULTSFive men underwent excision and closure of a urethrorectal fistula with diverting colostomy. In 4 men (80%) urinary continence subsequently returned with adequate sphincter tone, while in 1 (20%) with perineal trauma and active proctitis the fistula recurred 6 weeks after surgery. CONCLUSIONS: Urethrorectal fistulas are rare and surgically challenging. The transsphincteric, transanal surgical approach provides many advantages, including easy access and identification of the fistula tract, good surgical exposure, adequate resection to well vascularized tissue and access to several vascularized flaps for interposition between the repaired urinary and gastrointestinal tracts.

Adult↗
PubMed2006

Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases.

BACKGROUND: Evidence that a deficient innate immune response toward the bacterial flora of the gut plays a role in the pathogenesis of inflammatory bowel disease (IBD) is growing. This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD. METHODS: Thirty-five single nucleotide polymorphisms (SNP) in TLR1-10 were identified from public databases. 284 IBD parent-child trios and a second independent cohort of 285 IBD patients and 191 healthy controls were genotyped with polymerase chain reaction-restriction fragment length polymorphisms. Patients were pooled for genotype-phenotype analyses. RESULTS: Although none of the SNPs was involved in disease susceptibility, a number of variants influenced the disease phenotype. A positive association between TLR1 R80T and pancolitis in UC (P = .045, OR [95% CI] 2.844 [1.026-7.844]) was found. The TLR2 R753G SNP was also associated with pancolitis (P = .027, OR [95% CI] 4.741 [1.197-18.773]). The relative risks for heterozygous patients to develop pancolitis were 5.8 and 3.3 for R80T and R753G, respectively. There was a negative association between TLR6 S249P and ulcerative colitis with proctitis only (P = .026, OR [95% CI] 0.223 [0.096-0.705]). In CD, we found a negative association between ileal disease involvement and TLR1 S602I (P = .03, OR [95% CI] 0.522 [0.286-0.950]). CONCLUSION: TLR2 and its cofactors TLR1 and TLR6 are involved in the initial immune response to bacteria by recognizing peptidoglycan. An association between nonsynonymous variants in the TLR1, -2, and -6 genes and extensive colonic disease in UC and CD was found. Our findings further highlight the role of an abnormal innate immune response in the pathogenesis of IBD.

Adult↗
PubMed2006

Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study).

BACKGROUND: The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS: Patients diagnosed with inflammatory bowel disease (IBD) or possible IBD in southeastern Norway during the period 1990-1994 were followed prospectively for 5 years. The evaluation at 5 years included an interview, clinical examination, laboratory tests, and colonoscopy. RESULTS: Of 843 patients diagnosed with IBD, 454 patients who had definite UC and for whom there were sufficient data for analysis were alive 5 years after inclusion in the study. The frequency of colectomy in this population was 7.5%. Forty-one percent of the patients were not taking any kind of medication for IBD at 5 years. Of the patients initially diagnosed with proctitis, 28% had progressed during the observation period, 10% to extensive colitis. The majority of the patients (57%) had no intestinal symptoms at 5 years, and only a minority (7%) had symptoms that interfered with everyday activities. Among the patients who underwent colonoscopy at the 5-year visit, symptoms were frequently reported in patients without macroscopic inflammation (44%). A relapse-free course was observed in 22% of the patients. A decrease in symptoms during the follow-up period was the most frequent course taken by the disease and was observed in 59% of the cases. The extent of disease was unrelated to symptoms at 5 years and also to relapse rate and course of disease during the 5-year period. CONCLUSIONS: The disease course and prognosis of UC appears better than previously described in the literature. The frequency of surgery was low, and only a minority of the patients had symptoms that interfered with their everyday activities 5 years after diagnosis.

Adolescent↗
PubMed2005

Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999).

OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).

Adolescent↗
PubMed2005

Complications of radiotherapy: improving the therapeutic index.

For every course of radiotherapy treatment, the potential benefit has to be weighed against the risk of normal tissue damage. Radiation-induced proctitis during and after radical radiotherapy for prostate cancer can be decreased by reducing both the size of the target volume and the margins required around this volume. In the future, target volumes could be reduced by both CT/MRI co-registration and dose painting using MR spectroscopy of choline and citrate in the prostate. Improved immobilisation and image-guided radiotherapy should allow reduced margins without compromising the effectiveness of treatment. Similarly, in breast radiotherapy treatment, lung and cardiac complications can be reduced by better patient positioning and ensuring that doses to the heart and lung are minimised during radiotherapy treatment planning. Cosmesis can be improved by using 3D breast planning techniques rather than the conventional 2D approach. These ongoing improvements and developments in radiotherapy treatment planning are leading to treatments which offer both better tumour volume coverage, and are minimising the risk of treatment-related complications. In time, these changes should allow the escalation in dose delivered to the tumour volume with the potential for increased cure rates.

Breast Neoplasms↗
PubMed1991

Review article: new developments in the use of 5-aminosalicylic acid in patients with inflammatory bowel disease.

Sulphasalazine is composed of sulphapyridine and mesalazine (5-aminosalicylic acid, 5-ASA or mesalazine) joined by an azo bond. Sulphasalazine has been used clinically for 40 years but less than 10 years ago it was recognized that the active moiety is 5-ASA. Sulphapyridine appears to act only as a carrier molecule to deliver mesalazine to the bowel, yet it is the sulphapyridine which appears to be responsible for many of the adverse effects observed with sulphasalazine. Normally, mesalazine is rapidly absorbed from the upper gastrointestinal tract. Since the action of mesalazine is thought to be locally at the site of disease in the intestine, the 5-ASA must be 'protected' to ensure its release in the terminal ileum and colon, the site of bowel inflammation in patients with Crohn's disease or ulcerative colitis. Recent clinical studies have confirmed the efficacy of topical (suppositories and enemas) therapy for ulcerative proctitis and left-sided colitis; oral mesalazine has been proven to be useful for the treatment of acute ulcerative colitis and for the maintenance of remission. There is preliminary evidence for the clinical usefulness of mesalazine in acute Crohn's disease as well as for the maintenance of remission.

Aminosalicylic Acids↗
PubMed2005

Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitis.

BACKGROUND: Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. AIM: To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. METHODS: A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. RESULTS: Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. CONCLUSION: Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone.

Administration, Oral↗
PubMed2005

Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis.

BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Administration, Rectal↗
PubMed2006

Review article: aminosalicylates for distal colitis.

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure and therefore may be effectively treated with topical treatment. This allows the delivery of the active drug directly to the site of inflammation, limiting the systemic absorption and the potential side effects. Topical aminosalicylate therapy is the most effective approach, provided that the formulation reaches the upper extent of the disease. Suppositories should be considered the treatment of choice for proctitis and distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker clinical and endoscopic remission and was better tolerated than a 500-mg suppository twice daily. Enemas, foams and gel, thanks to their proximal spread, should be the treatment of choice for proctosigmoiditis and left-sided colitis. Oral aminosalicylates are less effective than topical therapies for patients with active disease; however, a combination of oral and topical aminosalicylates can be successfully tried in refractory patients. Topical aminosalicylates also play an important role in the maintenance of remission, and the combination of oral plus rectal 5-aminosalicylate is superior to the single agent. Patients who prefer not to continue on long-term rectal therapy can be treated with oral aminosalicylates.

Aminosalicylic Acids↗
PubMed2006

Review article: induction therapy for patients with active ulcerative colitis.

5-aminosalicylic acid (mesalazine) is considered first-line therapy for active mild-moderate, left-sided or extensive ulcerative colitis. With modern delayed-release formulations, conventional doses are very well tolerated, and there is accumulating evidence that increasing the dose, to >4 g/day, leads to higher response rates and earlier symptom relief in patients with ulcerative colitis. There is evidence that combining oral and rectal (enema) formulations of 5-aminosalicylic acid leads to faster and higher remission rates. Despite the fact that clinical trials in ulcerative colitis have often used different endpoints, making it difficult to make objective comparisons, the evidence now strongly suggests that it is appropriate to start patients with mild or moderately active ulcerative colitis on doses of 5-aminosalicylic acid of at least 4 g/day. For those with extensive disease, adding rectal 5-aminosalicylic acid improves remission rates; the same seems likely to be true for limited disease, but robust evidence is lacking. Rectal 5-aminosalicylic acid may in fact be sufficient on its own for patients with active proctitis. Patients with mild-moderate ulcerative colitis who do not improve within 2 weeks of high-dose 5-aminosalicylic acid should have treatment augmented by oral steroids.

Administration, Oral↗
PubMed1985

Some short-term cell kinetic effects of ionizing radiation on mouse bladder urothelium.

Early morphological changes and the pattern of reactive proliferation of the hairless mouse urinary bladder urothelium after irradiation are reported. Groups of female hairless mice were anaesthetized with sodium pentobarbital and irradiated over the bladder region with 0, 10, 20 and 30 Gy. Control groups were sham-treated. Short-term cell kinetic changes were monitored using incorporation of tritiated thymidine and flow cytometry. Only minor radiation-induced alterations in the cell kinetic pattern were recorded, and no significant histomorphological changes were seen. However, a marked increase in the thymidine incorporation was seen in the control animals on the first day after anaesthesia. Radiation proctitis induced early deaths in the 30 Gy irradiated animals. The present results are in accordance with commonly accepted radiobiological theories, but not in agreement with results previously published by others.

Animals↗