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PubMedDate not supplied

Autoimmune hepatitis associated with the odour of fish food proteins: a causal relationship or just a mere association?

We present the case of a 15-year-old boy [HLA phenotype: A 1, 25 (10); B 18, 8; C 7; DR 17 (3), 6] with classic (type 1) autoimmune hepatitis presumably caused by a long-term exposure to the strong odour of food fed to a large number of tropical fish which that the boy kept in tanks in his bedroom. The boy presented with a history of recent symptoms of common cold, and a high cytomegalovirus-IgG titer, both known to activate proinflammatory cytokines. The patient's laboratory results and physical findings improved without specific treatment during his first stay in the hospital for several weeks, as well as when the thanks were removed from his bedroom while disease activity increased after his return home. This suggests that the association with fish food odour (putative volatile protein antigens) was not simply coincidental. Our patien's history is in agreement with the recently postulated pathomechanism of autoimmune hepatitis, according to which viral infections may trigger the disease in a genetically predisposed individuals persistently exposed to a constant antigenic stimulus, which results in ongoing allergic inflammation and finally develops into an immune process. The spontaneous remissions observed in our patient were characteristic of the natural course of autoimmune hepatitis and may reflect periods when he was not exposed to the eventually harmful effects of the odour of fish food proteins.

Adolescent↗
PubMed2005

Irrational use of antibiotics among university students.

STUDY OBJECTIVE: The aim of the presented study was to evaluate the knowledge, attitude and behaviour of antibiotic usage in the student groups of a University in a country where the antibiotics are taken without prescriptions. DESIGN: Out of 5345 students (excluding those from the Faculty of Medicine) of Ege University, 678 were chosen by systematic sampling methods. The sampling group was divided into two groups. Group A included students from the Faculties of Pharmacy and Dentistry and Group B was composed of students of all other faculties. A questionnaire was used. MAIN RESULTS: The mean age was 21.0+/-3.0 and 58% were females. The aim of antibiotic use for common cold was 83.1% (P>0.05) and, to decrease fever was 32.1% (P<0.05) in both Groups. In Group A 36.1% and in Group B 44.9% of the respondents started antibiotics by themselves when they were ill (P>0.05) although 89.1% of both groups agree that antibiotics should be started with doctors' prescription. During their last infection in Group A 11.7% and in Group B 27.3% of the respondents used the same antibiotic as previously prescribed by their doctors and the use of antibiotics as advised by the doctors during their last infection was 50.8% in Group A and 35.3% in Group B. CONCLUSIONS: The use of antibiotics are found to be irrational among university students. National education programmes about the dangers of irrational antibiotic use and restriction of antibiotics without prescriptions should be the priority. This study indicated that knowledge regarding antibiotics cannot be evaluated alone since it did not always correlate with behaviour.

Adolescent↗
PubMed2005

Children's Health Care in the First National Healthcare Quality Report and National Healthcare Disparities Report.

BACKGROUND: The first National Healthcare Quality Report (NHQR) and National Healthcare Disparities Report (NHDR) are landmark events for children's health care quality and are expected to stimulate local measurement, benchmarking, and quality improvement efforts. METHOD: The authors select findings from the NHQR and NHDR, focusing on topics reflecting a range of health care and health care settings affecting children. They highlight disparities by race/ethnicity, socioeconomic status, and insurance source. They critique the first NHQR and NHDR from a child health perspective. SELECT NHQR/DR FINDINGS: Quality-of-care issues in the effectiveness domain were identified for black infant mortality, low and very low birth weight rates, antibiotic use for the common cold, and childhood hospitalizations for asthma. Immunization rates have improved. Patient centeredness and timeliness results vary by race, ethnicity and income. The NHDR found that Hispanic and low-income children are most likely to be uninsured for part of the year. Groups of children most likely to have public coverage are American Indian/Alaska native, black, and Hispanic. CRITIQUE OF REPORTS: The structure and criteria used for the first reports limit their usefulness from a child health perspective. A basic problem is that the conceptualizations of health and health care that are driving national initiatives on quality are based largely on an adult chronic care model focused on conditions with high expenditures as treated in the mainstream health care delivery system. CONCLUSION: NHQR and NHDR provide essential information on children's health care quality. Future reports can be improved by including child-relevant perspectives in priority-setting and data-gathering efforts.

Adolescent↗
PubMed1988

Plural medicine in Sri Lanka: do Ayurvedic and Western medical practices differ?

In Sri Lanka, as in India, two formally structured systems of medicine exist side by side. While Western-style biomedicine is believed to be useful, Ayurvedic medicine is well established and commonly used. Underlying one explanation for the persistence of such plural medical systems is a functional theory, suggesting that each system is used for different treatments, diseases, or for the ideological, linguistic or social characteristics of the physician. In part, Ayurvedic and Western medicine may persist because their practitioners provide distinctly different services. We tested part of this functional explanation by sending trained 'pseudo-patients' to 764 Ayurvedic and allopathic physicians across Sri Lanka. 'Patients' reported symptoms of common cold, diarrhea or back pain, and recorded after leaving the clinic many aspects of history-taking, diagnostic procedures and physician-patient interaction. Medicines prescribed were later analyzed by a laboratory. We found, basically, no significant differences between the medical practices of sampled Ayurvedic and Western-style physicians, with one exception. While both types spend 3-4 min asking four questions and doing two or three physical examination procedures, and while both prescribe, overwhelmingly, only Western medicines, the allopathic physicians give drugs, that, from the point of view of Western medicine, either 'help' or 'harm' and Ayurvedic physicians prescribe 'neutral' medicines. While we have not directly tested the entire functional explanation we suggest that a structural explanation of the persistence of two systems of medicine may be more valid. Ayurvedic and Western medicine continue in Sri Lanka because they, as institutions, are linked to the social, economic and political structure of the society. Thus, survival is based, not on what a physician does in his practice but upon the power of his medical profession to control medical territory.

Back Pain↗
PubMed1988

Group A streptococcal infection in children younger than three years of age.

We evaluated 758 sick children younger than 3 years of age for Group A beta-hemolytic streptococcal (GABHS) upper respiratory infection (URI) to determine the usual clinical presentation of the disease in this age group, indications for culture and the optimal site(s) from which to isolate the organism. GABHS infection was documented in 35 subjects (4.6%). The classic presentation (as proposed in the 1940s) of GABHS URI in children younger than 3 years of age was not confirmed by this study. In 32 of the GABHS cases there were pharyngitis, common cold symptoms or both, and these were associated with acute otitis media 10 times and with otitis media with effusion 3 times. Clinical impetigo was associated with GABHS URI (4 of 32 cases). GABHS URI would not have been documented in 6 of 32 cases if cultures of the anterior nares had not been performed. Children between 18 and 36 months of age were more likely to have GABHS disease than were younger children. Hoarseness and vomiting occurred less frequently in children younger than 36 months with GABHS infection than in those of that age who had non-beta-hemolytic streptococcal illnesses. A history of two or more siblings at home or a family member with a recent streptococcal infection and the presence of irritability, a reddened throat or palate or uvular edema were each associated with GABHS URI. We concluded that sick children between 18 and 36 months of age with a reddened throat should have cultures taken of the throat and anterior nares for GABHS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriological Techniques↗
PubMed2006

Intranasal zinc and anosmia: the zinc-induced anosmia syndrome.

OBJECTIVE: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described. METHODS: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing. RESULTS: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection. CONCLUSIONS: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.

Administration, Intranasal↗
PubMed1994

[A surveillance on acute respiratory infection].

History prospective methods were employed in this surveillance on acute respiratory infection (ARI) in four villages in Ping Yi and Gao Mi counties. One thousand-one hundred-and sixty four households, 4,379 individuals with 4365.92 person-years were followed up for ARI. The incidence of ARI was 0.4542 episodes/person-year and the household incidence rate was 68.99%. No death case of ARI occurred during the surveillance period. Of all the 18 ARI diseases under surveillance the three diseases with highest incidence were common cold, upper respiratory tract infection and bronchitis. These three diseases all showed obvious family clustering tendency. The incidence of ARI was highest in children under 1 year of age (1.3403 episodes/person year), followed by 2-6 year age-group. The lowest was in 20-29 year age-group (0.2885 episodes/person-year). There was no significant difference between sexes. The ARI incidence in spring (0.18024 episodes/person-season) was higher than in other seasons, with the peak between March and April. The hospital attending rate was 90.07%. Among the patients, 80.05% received antibiotics, 13.06% received hormone, 2.10% received intravenous rehydration. ARI accounted for 24.83% of all the out-patients in township hospitals, 19.05%, of which were preschool children. For these children, 70.78% were using antibiotics, 23.31% using hormone, 10.06% using intravenous rehydration. Of the patients, the risk factors of ARI included low birth weight, difficult labour, malnutrition, illiteracy, low income, poor ventilation and lighting of the living room, poor living condition and cigarette smoking. The results presented will be of great significance to policy-making of ARI control in Shandong Province.

Acute Disease↗
PubMed2004

Recent advances in rhinovirus therapeutics.

Human rhinoviruses are the major causative agents of the common cold. Because there are greater than 100 viral serotypes, little immunological protection is afforded to humans by prior rhinovirus exposure, which accounts for the high incidence of infection. In most cases, rhinovirus leads to a short self-limiting illness. However, for asthmatics, the elderly and immunocompromised patients, rhinovirus infection can lead to life-threatening complications. This has spurred a consistent effort over recent decades to identify effective treatments and preventions for rhinovirus infection. While some work has focused on alleviating the symptoms induced as a result of inflammatory pathways stimulated by rhinoviruses, the majority of the research has been focused on limiting or preventing viral infection altogether. Various approaches have been taken to halt rhinovirus infection. Prevention of virus-cell interaction has been the aim of research on viral capsid binders and cell receptor blockers. Interference with correct viral protein processing is the goal of the design and testing of protease inhibitors. Current work is attempting to interfere with viral RNA replication by testing silencing RNA molecules. In this review, we will discuss recent advances in the development and testing of human rhinovirus therapeutics.

Antiviral Agents↗
PubMed1987

Influenza B in households: virus shedding without symptoms or antibody response.

In the fall of 1983, 53 households were enrolled in a double-blind trial of alpha 2-interferon as an intranasal spray to prevent common colds. During the winter/spring of 1984, 26 households were infected with influenza type B, as shown by isolation of the virus (19 households) and/or significant antibody titer rises (seven households). Interferon did not prevent influenza B infection or modify resulting illness. Of 37 persons shedding virus, 12 were asymptomatic. All were older than age 12 years, and 10 did not respond with antibody by any of the five test methods employed (complement fixation, hemagglutination inhibition, enzyme-linked immunosorbent assay (ELISA), neutralization, and Western blot). In contrast, of 13 symptomatic persons shedding virus from whom sera were available, 11 had significant antibody titer rises. Infection rates were highest among teenagers, but also surprisingly high among the 11 persons observed who were aged 50 years or older, four of whom were infected. The case-to-case interval in household transmission varied between one and nine days. Longer intervals of one, two, and four months between infections among family members were also observed, suggesting repeated introductions. Neither virus isolation alone nor serologic tests was sufficient to estimate infection rates.

Adolescent↗
PubMed2004

Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council.

The 1948 report of the British Medical Research Council's randomized trial of streptomycin for pulmonary tuberculosis is widely regarded as marking the beginning of the modern history of controlled clinical trials. Four years earlier, however, a methodologically sophisticated multicentre trial conducted under the aegis of the Medical Research Council was reported, which assessed the effects of the antibiotic patulin on the course of common colds. Philip D'Arcy Hart and Joan Faulkner (later Joan Doll) were the secretary and assistant secretary, respectively, to the committee overseeing the trial, and they clearly recognized the importance of preventing foreknowledge of allocations from those admitting patients to the study. To do this and to 'muddle people up', they and Ruth D'Arcy Hart devised a scheme involving the use of two patulin groups and two placebo groups, allocating patients to one of these four groups using strict rotation. Philip D'Arcy Hart believes that this study has been overshadowed by the celebrated streptomycin trial (for which he was also secretary to the oversight committee) because no beneficial effect of patulin was detected, and because the report of the streptomycin trial referred to the use of random sampling numbers to generate the allocation schedule. This article makes clear why we agree with Philip D'Arcy Hart that the 1944 patulin trial deserves wider recognition as the first well controlled, multicentre clinical trial to have been conducted under the aegis of the British Medical Research Council. This status is reflected in the International Journal of Epidemiology's reproduction of the full text of the trial report in this issue of the journal.

Common Cold↗
PubMed2005

Comparative host gene transcription by microarray analysis early after infection of the Huh7 cell line by severe acute respiratory syndrome coronavirus and human coronavirus 229E.

The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) at the cellular level is unclear. No human cell line was previously known to be susceptible to both SARS-CoV and other human coronaviruses. Huh7 cells were found to be susceptible to both SARS-CoV, associated with SARS, and human coronavirus 229E (HCoV-229E), usually associated with the common cold. Highly lytic and productive rates of infections within 48 h of inoculation were reproducible with both viruses. The early transcriptional profiles of host cell response to both types of infection at 2 and 4 h postinoculation were determined by using the Affymetrix HG-U133A microarray (about 22,000 genes). Much more perturbation of cellular gene transcription was observed after infection by SARS-CoV than after infection by HCoV-229E. Besides the upregulation of genes associated with apoptosis, which was exactly opposite to the previously reported effect of SARS-CoV in a colonic carcinoma cell line, genes related to inflammation, stress response, and procoagulation were also upregulated. These findings were confirmed by semiquantitative reverse transcription-PCR, reverse transcription-quantitative PCR for mRNA of genes, and immunoassays for some encoded proteins. These transcriptomal changes are compatible with the histological changes of pulmonary vasculitis and microvascular thrombosis in addition to the diffuse alveolar damage involving the pneumocytes.

Apoptosis↗
PubMed2004

Rhinovirus detection: comparison of real-time and conventional PCR.

Rhinoviruses are important human respiratory viruses and the major causative agents of the common cold. Historically, detection of rhinovirus has been by virus culture and this was significantly improved by the use of PCR assays. Recently real-time PCR was developed but to date there have been no reported comparisons of conventional and real-time PCR assays for detection of rhinovirus. In this study, we first compared real-time PCR (SYBR Green I) to conventional PCR for the detection of rhinovirus in serially diluted standard DNA and rhinovirus stock to determine the limits of detection. Next, assays were compared for sensitivity to detect rhinovirus in cell culture with a known number of infected cells. Finally, the assays were compared using clinical samples known to contain rhinovirus. Real-time PCR was 10-fold more sensitive than conventional PCR to detect rhinovirus in standard DNA and in virus stock and >10-fold more sensitive to detect rhinovirus in cultured cells. Real-time PCR was significantly superior for detection of rhinovirus in patients' nasal aspirates (sensitivity 72% versus 39%, P < 0.05). In summary, we found that real-time PCR was more sensitive than conventional PCR and reduced post-PCR processing. Hence, real-time PCR is suitable for both research and clinical purposes.

Common Cold↗
PubMed2001

The relationship between atopic status and IL-10 nasal lavage levels in the acute and persistent inflammatory response to upper respiratory tract infection.

We examined the influence of atopy on virus-induced airway inflammation by comparing the nasal response to naturally acquired upper respiratory tract infection in atopic and nonatopic subjects by measurement of cytokine, chemokine, and mediator levels in nasal lavage from 44 adults (23 atopic) taken during the acute and the convalescent phases of the common cold. Nasal aspirates were examined for the presence of upper respiratory viruses by RT-PCR. In atopic and nonatopic subjects there were increased levels of IL-1beta, IL-6, IL-8, TNF-alpha, RANTES, sICAM-1, MPO, ECP, IL-10, and IFN-gamma in nasal lavage during the acute compared with the convalescent phase (p < 0.001). During the acute phase histamine levels were significantly higher in the atopic than in the nonatopic subjects (p < 0.05), whereas IL-10 levels were significantly greater in the nonatopic than in the atopic subjects (p < 0.05). At convalescence levels of IL-1beta, IL-6, sICAM-1, ECP, RANTES and albumin were significantly higher in the atopic group (p < 0.05). An upper respiratory tract virus was found in 27 volunteers (61%) during the acute stage and in two volunteers (4%) at convalescence. We conclude that virus-induced inflammatory changes within the nose are more prolonged in atopic than in nonatopic subjects and that this is associated with reduced IL-10 levels in atopic compared with nonatopic subjects during the acute phase of upper respiratory tract infection.

Acute-Phase Proteins↗
PubMed2000

In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses.

BACKGROUND: We tested the in vitro activity of pleconaril and AG7088 against five numbered human rhinovirus (HRV) serotypes and 46 clinical HRV isolates of undefined serotype recovered from patients with common colds. Antiviral effect of pleconaril and AG7088 were assessed by cytophathic effect (CPE) inhibition assays in Ohio HeLaI cells using microscopic and spectrophotometric methods. Both compounds were tested at concentrations of 1.0, 0.1 and 0.01 microg/ml. For the numbered HRV serotypes, the median EC(50) value determined by the microscopic CPE inhibition was slightly better for AG7088 compared to pleconaril (P=0.02) but was similar by spectrophotometric assay (P=0.15). For clinical HRV isolates the median EC(50) value determined microscopically was 0.01 microg/ml range, <0.01-0.04 microg/ml) for AG7088 compared to 0.07 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). The median EC(50) value determined by spectrophotometric assay was 0.01 microg/ml (range, <0.01-0.04 microg/ml) for AG7088 compared to 0.04 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). By either the microscopic or spectrophotometric methods the median EC(50) value of AG7088 was <1.0 microg/ml for all isolates and was >10.0 microg/ml of pleconaril for approximately 9% of isolates. In vitro AG7088 appeared to be more potent and to have a broader antirhinoviral spectrum than pleconaril among clinical HRV isolates. The clinical relevance of these in vitro results needs to be determined in controlled clinical trials.

Antiviral Agents↗
PubMed2002

Acute upper airway infections.

Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.

Acute Disease↗
PubMed2005

An evaluation of Echinacea angustifolia in experimental rhinovirus infections.

BACKGROUND: Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection. METHODS: Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis. RESULTS: There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer. CONCLUSIONS: The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Adult↗
PubMed2003

Comparison of rhinometric measurements methods in intranasal pathology.

The objective of this study was to determine how well different rhinometric measurement methods identify intranasal changes during acute viral rhinitis. A total of 69 patients acutely ill with the common cold were examined. Acoustic rhinometry (AR), rhinomanometry (RMM), nasal PEF (nPEF) and Visual Analogue Scale (VAS) recordings were performed before the subjects became ill and after the onset of the infection, on days 3 and 10. In AR the minimal cross-sectional area and nasal cavity volumes decreased in a statistically significant manner during the early stage of infection (20.0% vs. 20.4% lower than baselines), and at the end of the infection the values were normalizing towards the baseline values, although still 7.2% vs. 10.4% lower than baselines (p < 0.05). In RMM the total resistances during expiration and inspiration strongly increased, 39.7% vs. 41.6% higher than baselines on day 3. On day 10 the resistances were normalizing slowly but remained 34.1% and 41.5% higher than baselines (p < 0.05). In nPEF the decrease in rates was also seen on day 3 (25.0% lower than baseline) and recovery in rates on day 10 (only 3.1% lower than baseline, p < 0.05). The changes in VAS were similar to those seen in objective rhinometric measurements. Statistically and clinically significant correlations were calculated within AR parameters (r = 0.96) and RMM parameters (r = 0.98), other rhinometric parameters did not correlate in a clinically significant manner (r < 0.40). We concluded that these 4 rhinometric methods support each other very well in pathological noses, and the methods employed identify intranasal changes very sensitively during an intranasal mucosal pathology.

Adult↗
PubMed1996

[Drug induced hemolytic anemia associated with agranulocytosis].

A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know.

Adult↗