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Background: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV 1 /forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups., Methods: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV 1 /FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV 1 /FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated., Findings: The prevalence of the four lifetime spirometry patterns was as follows: low FEV 1 /FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV 1 /FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV 1 /FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea., Interpretation: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV 1 /FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age., Funding: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline., Competing Interests: Declaration of interests CJL, EHW, AJL, DSB, MJA, JLP, and SCD hold an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA holds investigator-initiated grants from Pfizer, Boehringer Ingelheim, and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received speaker's fees from GlaxoSmithKline. AJL has received non-financial support from Primus Pharmaceuticals for unrelated research. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk., Method: A cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools., Results: Rugby Union was delivered in 81% ( n = 234 of 288) of state-funded secondary school physical education curricula, including 83% ( n = 229 of 275) of state-funded secondary school boys' and 54% ( n = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% ( n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% ( n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum., Conclusion: Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 White, Batten, Howarth, Magrath, Piggin, Millward, Parry, Lang, Bullingham, Pearce, Morales, Turner, Humphries, Hardwicke, Anderson, Kirkwood and Pollock.)

Background: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS)., Methods: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV 1 , forced vital capacity [FVC], FEV 1 /FVC ratio, forced expiratory flow at 25-75% of FVC [FEF 25-75% ], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV 1 /FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated., Results: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV 1 /FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV 1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF 25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV 1 /FVC ratio was only significant among smokers (p interaction =0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV 1 /FVC ratio or COPD., Interpretation: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking., Funding: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline., Competing Interests: Declaration of interests DSB, JLP, MJA, EHW, AJL, CJL, and SCD hold an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim, and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received a speaker's fee from GlaxoSmithKline. BRT has received unrelated speaker and consultancy fees from Chiesi, Mundipharma, and 4D medical. AJL has received non-financial support from Primus Pharmaceuticals for unrelated research. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Many studies have investigated factors that predict a return to sport participation after anterior cruciate ligament (ACL) reconstruction, but it is unclear whether the same factors are associated with a return to preinjury level of sport performance., Purpose: To identify factors that contribute to an athlete's return to preinjury level of performance after ACL reconstruction., Study Design: Cohort study; Level of evidence, 2., Methods: A cohort of 222 patients (132 male, 90 female) who had ACL reconstruction surgery and completed a 12-month postoperative assessment were followed out to a mean 3 years (range, 2-4 years) to determine whether they had returned to their self-reported preinjury levels of sport performance. Rates of return to preinjury performance were calculated. Measures that had been recorded at the 12-month postoperative review-demographic (age, sex), sport activity level (Marx Activity Rating Scale, return to competition sport), knee laxity, limb symmetry (single and triple crossover hop), subjective function/symptoms (International Knee Documentation Committee subjective), and psychological readiness (Anterior Cruciate Ligament Return to Sport After Injury scale)-were compared between patients who returned to their preinjury levels of performance and those who did not. Univariate and multivariate logistic regression models were also used to prospectively determine the association between these measures and return to preinjury level of sport performance., Results: A total of 135 (61%) patients reported that they had returned to their preinjury levels of performance, with return rates similar between males (59%) and females (63%) and between those who had returned to competition at 12 months (62%) and those who had not (60%). There was no significant age difference between patients who returned to their preinjury levels of sport performance and those who did not; however, higher psychological readiness ( P < .0001), greater limb symmetry ( P < .05), higher subjective knee scores ( P = .01), and a higher activity level ( P < .04) were all associated with a return to performance. In the multivariate model, psychological readiness was the only variable that remained a significant predictor (odds ratio = 1.03; 95% CI, 1.01-1.04; P < .0001)., Conclusion: A majority of athletes who returned to sport after ACL reconstruction reported that their performance was comparable with preinjury. Having a greater psychological readiness to return during rehabilitation was the most significant predictor of a subsequent return to comparable performance.

Objective: To evaluate the use of urinary biomarkers to assess exposure of cats to environmental tobacco smoke (ETS)., Animals: 61 healthy client-owned cats (19 from households in which smoking was reported and 42 from households in which there was no smoking)., Procedures: Urine samples were obtained from each cat and assayed for total nicotine (nicotine plus nicotine glucuronide) and total cotinine (cotinine plus cotinine glucuronide) content by use of gas chromatography-mass spectrometry. In addition, total urinary content of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, was measured by use of gas chromatography with nitrosamine-selective detection., Results: Cats from households in which smoking was reported had significantly higher concentrations of total nicotine (70.4 ng/mL), total cotinine (8.53 ng/mL), and total NNAL (0.0562 pmol/mL) in urine, compared with concentrations for cats that lived in households in which there was no smoking (4.89 ng/mL, 0.74 ng/mL, and 0.0182 pmol/mL, respectively)., Conclusions and Clinical Relevance: Analysis of these data provided biochemical evidence of exposure to ETS and uptake of tobacco-specific carcinogens by cats that live in households with smokers. Biomarkers could facilitate investigation of the health effects of ETS in cats and other species.

The Xenopus laevis nuclear receptor BXR has recently been shown to be activated by a class of endogenous benzoate metabolites, indicating the presence of a novel and unsuspected benzoate ligand-dependent signalling pathway. The receptor is expressed ubiquitously in blastula and gastrula stage embryos, and its expression declines during neurula stages. In order to examine further this novel vertebrate signalling system, we have examined the expression of the BXR gene in tailbud stage embryos and adults. We show here that in Xenopus tailbud stage embryos expression is restricted to the hatching gland, suggesting a role in hatching gland function. Neither BXR nor a BXR-VP16 fusion is sufficient to specify hatching gland in neurally-induced tissue. In adults, BXR expression is abundant in the brain and gonads. This expression pattern in adults is distinct from any of the putative mammalian homologues. A nuclear receptor that mediates benzoate signalling has yet to be found in mammals.

The genes for the rod and rod-like green cone opsins in two avian species, the budgerigar, Melopsittacus undulatus, and the mallard duck, Anas platyrhynchus, are identified on the basis of amino acid identity with the equivalent chicken sequences and their placement into a single phylogenetic clade with the rod and rod-like green cone opsin genes from other vertebrate species. Since the two bird species studied are taxonomically quite distinct, this would indicate that this rod-like green cone opsin gene, although absent in mammals, is common in the Aves. The two avian pigments differ consistently at site 122, consistent with the reported role of this site in determining the rate of metarhodopsin II formation and decay in rod and cone pigments. Candidate sites are identified to compensate for the known spectral effects of substitution at this site.

Microspectrophotometric examination of the retinal photoreceptors of the budgerigar (shell parakeet), Melopsittacus undulatus (Psittaciformes) and the zebra finch, Taeniopygia guttata (Passeriformes), demonstrate the presence of four, spectrally distinct classes of single cone that contain visual pigments absorbing maximally at about 565, 507, 430-445 and 360-380 nm. The three longer-wave cone classes contain coloured oil droplets acting as long pass filters with cut-offs at about 570, 500-520 and 445 nm, respectively, whereas the ultraviolet-sensitive cones contain a transparent droplet. The two species possess double cones in which both members contain the long-wave-sensitive visual pigment, but only the principal member contains an oil droplet, with cut-off at about 420 nm. A survey of the cones of the pigeon, Columba livia (Columbiformes), confirms the presence of the three longer-wave classes of single cone, but also reveals the presence of a fourth class containing a visual pigment with maximum absorbance at about 409 nm, combined with a transparent droplet. No evidence was found for a fifth, ultraviolet-sensitive receptor. In the chicken, Gallus gallus (Galliformes), the cone class with a transparent droplet contains "chicken violet" with maximum absorbance at about 418 nm. The rods of all four species contain visual pigments that are spectrally similar, with maximum absorbance between about 506 and 509 nm. Noticeably, in any given species, the maximum absorbance of the rods is spectrally very similar to the maximum absorbance of the middle-wavelength-sensitive cone pigments.

The potential role of humoral immunity in regulating intrapulmonary growth of Legionella pneumophila in the immunocompetent host was investigated using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with a virulent strain of L. pneumophila (10(6) bacteria per mouse) resulted in the recruitment of B lymphocytes into the lung and the development of anti-L. pneumophila Ab. Opsonization of L. pneumophila in vitro with anti-L. pneumophila-specific mAb resulted in a significant decrease in intrapulmonary growth of the bacteria at 24 to 72 h postinfection. Transmission electron microscopic analysis of lung tissue from L. pneumophila- infected mice demonstrated that while there was no significant difference between phagocytosis of the unopsonized and opsonized L. pneumophila by alveolar macrophages at 24 h postinfection, phagocytosis of opsonized bacteria by alveolar mononuclear phagocytic cells was significantly enhanced at 48 h postinfection. Depletion of A/J mice of complement before intratracheal inoculation of opsonized L. pneumophila (10(6) bacteria per mouse) did not significantly alter intrapulmonary growth of L. pneumophila. These results suggest that anti-L. pneumophila Ab, produced during replicative L. pneumophila lung infections, may regulate intrapulmonary growth of L. pneumophila in the immunocompetent host by decreasing the viability of extracellular L. pneumophila and by enhancing phagocytosis of the bacteria by alveolar mononuclear phagocytic cells by a complement-independent mechanism.

Squamous cell carcinoma of the midventral abdominal pad was diagnosed in 3 male gerbils. Two of the gerbils had raised, ulcerated masses on the midventral portion of the abdomen. The first gerbil was 2 years old, and an excisional biopsy was performed. The gerbil survived 23 months after surgery without evidence of metastasis or clinical signs of local recurrence. At necropsy, neoplastic squamous cells were seen on histologic examination of the surgery site. The second gerbil was 4 years old, and surgical excision of the tumor with concurrent castration was curative. The third gerbil was moribund on admission, perhaps because ulceration of the tumor may have allowed bacteria to invade the tissue, resulting in septicemia and disseminated intravascular coagulation. These gerbils illustrated that hematologic, radiographic, and biochemical testing in rodents can be useful and that excision of squamous cell carcinoma tumors of the midventral abdominal pad of gerbils can be an effective treatment.

On the basis of physiological localization, broad substrate specificity and energy dependence, the role of the kidney P-glycoprotein was tested in the energy-dependent renal secretion of organic cations. P-glycoprotein-enriched vesicles from Cl 1D/VCR [a multidrug-resistant (MDR) cell line] displayed enhanced transport of the MDR drug vinblastine and the organic cation cimetidine but not of the organic cation tetraethylammonium (TEA) over that shown by vesicles prepared from the drug-sensitive parental line Cl 1D. An outwardly directed proton gradient stimulated TEA and cimetidine uptake by renal brush border membrane vesicles (BBMV) but this gradient did not enhance the uptake of these organic cations into Cl 1D/VCR vesicles. Vinblastine uptake was unaffected by the proton gradient in either vesicle preparation. An outwardly directed gradient of TEA enhanced the uptake of TEA into renal BBMV but did not do so in the case of Cl 1D/VCR vesicles. These data indicate that P-glycoprotein, which is normally energized by ATP hydrolysis, is incapable of catalyzing organic cation/proton exchange or organic cation/organic cation exchange, properties of the organic cation carrier of renal proximal tubule BBMV. The MDR substrates and modulators inhibited the uptake of vinblastine and cimetidine by Cl 1D/VCR vesicles and the uptake of cimetidine and TEA by renal BBMV. Several organic cations studied inhibited TEA and cimetidine uptake by renal BBMV but did not inhibit the uptake of vinblastine and cimetidine by Cl 1D/VCR vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Transgenic mice carrying the mouse mos proto-oncogene linked to a retroviral LTR develop hyperplasia of the Harderian glands. Enlargement of the glands is evident as early as 18 weeks after birth, with glands reaching up to 10 times their normal weight. Approximately 65% of the cases of hyperplasia occur bilaterally, and the majority of mice affected are male (66%). Elevated levels of mos expression are found in all Harderian glands of mice from the affected transgenic line, but not in glands of normal mice or a non-affected transgenic line, indicating that hyperplasia is dependent on mos expression. Histological examination of the tissue reveals a general involvement of the entire gland epithelium in hyperplastic growth, with no evidence of focal or malignant tumours. These observations show that in addition to neu, myc, ras and ret transgenes, mos, a member of the protein-serine/threonine kinase family of oncogenes, can induce Harderian gland hyperplasia, thus revealing an unusual response by this organ to various classes of oncogenes. Analysis of fos, jun, myc and ets oncogene RNA in mos-induced hyperplastic Harderian glands shows that there are no consistent changes in the level of expression of these oncogenes, suggesting that mos acts via a mechanism other than by increasing the expression of these genes.