Modeling daily yields of milk, fat, protein, and lactose of New Zealand dairy goats undergoing standard and extended lactations.

This study aimed to assess the milk production data for New Zealand dairy goats in either a standard lactation (SL; ≤305 d in milk [DIM]) or extended lactation (EL; >305 and ≤670 DIM) using a random regression (RR) with third- and fifth-order Legendre polynomials, respectively. Persistency of EL was defined as (B/A) × 100, where A was the accumulated yield from d 1 to 305, and B was the accumulated yield from d 366 to 670. On average, goats in SL produced 1,183 kg of milk, 37 kg of fat, 37 kg of protein, and 54 kg of lactose. The average production of milk, fat, protein, and lactose in EL were 2,473 kg, 78 kg, 79 kg, and 112 kg, respectively. The average persistences for milk, fat, protein, and lactose yields during EL were 98%, 98%, 102%, and 96%, respectively. The relative prediction errors were close to 10% and the concordance correlation coefficients >0.92, indicating that the RR model with Legendre polynomials is adequate for modeling lactation curves for both SL and EL. Total yields and persistency were analyzed with a mixed model that included the fixed effects (year, month of kidding, parity, and proportion of Saanen) as covariates and the random effects of animal and residual errors. Effects of year, month of kidding, and parity were significant on the total yields of milk, fat, protein, and lactose for both SL and EL. The total milk yield of first-parity goats with SL was 946 kg and the total milk yield of second-parity goats with SL was 1,284 kg, making a total of 2,230 kg over 2 years. The total milk yield of a first-parity goat with EL was 2,140 kg. Thus, on average, a goat with SL for the first and second parity produced 90 kg more milk than a first-parity goat subjected to EL. However, a second-parity goat subjected to EL produced 43 kg more milk (2,639 kg) than a goat with SL following the second and third parity (1,284 kg + 1,312 kg). These data, along with the various other benefits of EL (e.g., fewer offspring born and reduced risk of mastitis, lameness, and metabolic problems in early lactation), indicate that EL as a management strategy holds the potential to improve dairy goat longevity and lifetime efficiency without compromising milk production.

Neonatal near-miss audits: a systematic review and a call to action.

BACKGROUND: Neonatal near-miss (NNM) can be considered as an end of a spectrum that includes stillbirths and neonatal deaths. Clinical audits of NNM might reduce perinatal adverse outcomes. The aim of this review is to evaluate the effectiveness of NNM audits for reducing perinatal mortality and morbidity and explore related contextual factors. METHODS: PubMed, Embase, Scopus, CINAHL, LILACS and SciELO were searched in February/2023. Randomized and observational studies of NNM clinical audits were included without restrictions on setting, publication date or language. PRIMARY OUTCOMES: perinatal mortality, morbidity and NNM. SECONDARY OUTCOMES: factors contributing to NNM and measures of quality of care. Study characteristics, methodological quality and outcome were extracted and assessed by two independent reviewers. Narrative synthesis was performed. RESULTS: Of 3081 titles and abstracts screened, 36 articles had full-text review. Two studies identified, rated, and classified contributing care factors and generated recommendations to improve the quality of care. No study reported the primary outcomes for the review (change in perinatal mortality, morbidity and NNM rates resulting from an audit process), thus precluding meta-analysis. Three studies were multidisciplinary NNM audits and were assessed for additional contextual factors. CONCLUSION: There was little data available to determine the effectiveness of clinical audits of NNM. While trials randomised at patient level to test our research question would be difficult or unethical for both NNM and perinatal death audits, other strategies such as large, well-designed before-and-after studies within services or comparisons between services could contribute evidence. This review supports a Call to Action for NNM audits. Adoption of formal audit methodology, standardised NNM definitions, evaluation of parent's engagement and measurement of the effectiveness of quality improvement cycles for improving outcomes are needed.

My Baby's Movements: a stepped-wedge cluster-randomised controlled trial of a fetal movement awareness intervention to reduce stillbirths.

OBJECTIVE: The My Baby's Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (the MBM intervention). DESIGN: Stepped-wedge cluster-randomised controlled trial. SETTING: Twenty-seven maternity hospitals in Australia and New Zealand. POPULATION: Women with a singleton pregnancy without major fetal anomaly at ≥28 weeks of gestation from August 2016 to May 2019. METHODS: The MBM intervention was implemented at randomly assigned time points, with the sequential introduction of eight groups of between three and five hospitals at 4-monthly intervals. Using generalised linear mixed models, the stillbirth rate was compared in the control and the intervention periods, adjusting for calendar time, study population characteristics and hospital effects. MAIN OUTCOME MEASURES: Stillbirth at ≥28 weeks of gestation. RESULTS: There were 304 850 births with 290 105 births meeting the inclusion criteria: 150 053 in the control and 140 052 in the intervention periods. The stillbirth rate was lower (although not statistically significantly so) during the intervention compared with the control period (2.2/1000 versus 2.4/1000 births; aOR 1.18, 95% CI 0.93-1.50; P = 0.18). The decrease in stillbirth rate was greater across calendar time: 2.7/1000 in the first versus 2.0/1000 in the last 18 months. No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident. CONCLUSIONS: The MBM intervention did not reduce stillbirths beyond the downward trend over time. As a result of low uptake, the role of the intervention remains unclear, although the downward trend across time suggests some benefit in lowering the stillbirth rate. In this study setting, an awareness of the importance of fetal movements may have reached pregnant women and clinicians prior to the implementation of the intervention. TWEETABLE ABSTRACT: The My Baby's Movements intervention to raise awareness of decreased fetal movement did not significantly reduce stillbirth rates.

Implementation and evaluation of a quality improvement initiative to reduce late gestation stillbirths in Australia: Safer Baby Bundle study protocol.

BACKGROUND: In 2015, the stillbirth rate after 28 weeks (late gestation) in Australia was 35% higher than countries with the lowest rates globally. Reductions in late gestation stillbirth rates have steadily improved in Australia. However, to amplify and sustain reductions, more needs to be done to reduce practice variation and address sub-optimal care. Implementing bundles for maternity care improvement in the UK have been associated with a 20% reduction in stillbirth rates. A similar approach is underway in Australia; the Safer Baby Bundle (SBB) with five elements: 1) supporting women to stop smoking in pregnancy, 2) improving detection and management of fetal growth restriction, 3) raising awareness and improving care for women with decreased fetal movements, 4) improving awareness of maternal safe going-to-sleep position in late pregnancy, 5) improving decision making about the timing of birth for women with risk factors for stillbirth. METHODS: This is a mixed-methods study of maternity services across three Australian states; Queensland, Victoria and New South Wales. The study includes evaluation of 'targeted' implementer sites (combined total approximately 113,000 births annually, 50% of births in these states) and monitoring of key outcomes state-wide across all maternity services. Progressive implementation over 2.5 years, managed by state Departments of Health, commenced from mid-2019. This study will determine the impact of implementing the SBB on maternity services and perinatal outcomes, specifically for reducing late gestation stillbirth. Comprehensive process, impact, and outcome evaluations will be conducted using routinely collected perinatal data, pre- and post- implementation surveys, clinical audits, focus group discussions and interviews. Evaluations explore the views and experiences of clinicians embedding the SBB into routine practice as well as women's experience with care and the acceptability of the initiative. DISCUSSION: This protocol describes the evaluation of the SBB initiative and will provide evidence for the value of a systematic, but pragmatic, approach to strategies to reduce the evidence-practice gaps across maternity services. We hypothesise successful implementation and uptake across three Australian states (amplified nationally) will be effective in reducing late gestation stillbirths to that of the best performing countries globally, equating to at least 150 lives saved annually. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the ACTRN12619001777189 database, date assigned 16/12/2019.

Climate change may restrict dryland forest regeneration in the 21st century.

The persistence and geographic expansion of dryland forests in the 21st century will be influenced by how climate change supports the demographic processes associated with tree regeneration. Yet, the way that climate change may alter regeneration is unclear. We developed a quantitative framework that estimates forest regeneration potential (RP) as a function of key environmental conditions for ponderosa pine, a key dryland forest species. We integrated meteorological data and climate projections for 47 ponderosa pine forest sites across the western United States, and evaluated RP using an ecosystem water balance model. Our primary goal was to contrast conditions supporting regeneration among historical, mid-21st century and late-21st century time frames. Future climatic conditions supported 50% higher RP in 2020-2059 relative to 1910-2014. As temperatures increased more substantially in 2060-2099, seedling survival decreased, RP declined by 50%, and the frequency of years with very low RP increased from 25% to 58%. Thus, climate change may initially support higher RP and increase the likelihood of successful regeneration events, yet will ultimately reduce average RP and the frequency of years with moderate climate support of regeneration. Our results suggest that climate change alone may begin to restrict the persistence and expansion of dryland forests by limiting seedling survival in the late 21st century.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Cross Lineage Rearrangement in Feline Enteropathy-Associated T-cell Lymphoma.

Feline enteropathy-associated T-cell lymphoma (EATL) type II is characterized by infiltration of the small intestinal mucosa with small T-cells with variable epitheliotropism and is often difficult to differentiate from inflammation. Polymerase chain reaction (PCR) to assess antigen receptor rearrangements (PARR) amplifies the T- (T-cell receptor gamma, TCRG) or B-cell (immunoglobulin heavy chain, IGH) antigen receptor genes and is used to differentiate EATL from inflammation. However, PARR does not determine lymphocyte phenotype, and clonal rearrangement of either or both the TCRG or IGH genes may be detected in neoplastic T-cells. The purpose of this study was to determine the incidence of cross lineage rearrangement in feline EATL type II. Using a diagnostic algorithm combining histology, immunohistochemistry, and PARR testing, 8 of 92 cases diagnosed as EATL type II at Michigan State University between January 2013 and June 2014 showed cross lineage rearrangement (8.7%). PARR for the IGH gene facilitates the diagnosis of cases histologically highly suggestive of EATL type II in which polyclonal rearrangement of the TCRG gene is detected.

A multicentre study of the precision and accuracy of the TruSlice and TruSlice Digital histological dissection devices.

BACKGROUND: Five key factors enabling a good surgical grossing technique include a flat uniformly perpendicular specimen cutting face, appropriate immobilisation of the tissue specimen during grossing, good visualisation of the cutting tissue face, sharp cutting knives and the grossing knife action. TruSlice and TruSlice Digital are new innovative tools based on a guillotine configuration. The TruSlice has plastic inserts whilst the TruSlice Digital has an electronic micrometre attached: both features enable these dissection factors to be controlled. The devices were assessed in five hospitals in the UK. MATERIAL AND METHODS: A total of 267 fixed tissue samples from 23 tissue types were analysed, principally the breast (n = 32) skin (30), rectum (28), colon (27) and cervix (17). Precision and accuracy were evaluated by measuring the defined thickness, and the consistency of achieving the defined thickness of tissue samples taken respectively. Both parameters were expressed as a total percentage of compliance for the cohort of samples accessed. RESULTS: Overall, the mean (standard deviation) score for precision was 81 (11) % whilst the accuracy score was 82 (11) % (both p < 0.05, chi-squared test), although this varied with type of tissue. Accuracy and precision were strongly correlated (rp = 0.83, p < 0.001). CONCLUSION: The TruSlice Digital devices offer an assured precision and accuracy performance which is reproducible across an assortment of tissue types. The use of a micrometre to set tissue slice thickness is innovative and should comply with laboratory accreditation requirements, alleviating concerns of how to tackle issues such as the 'measurement of uncertainty' at the grossing bench.

Expanding the phenotypic spectrum of ECEL1-related congenital contracture syndromes.

Using a combination of homozygosity mapping and whole-exome sequencing (WES), we identified a novel missense c.1819G>A mutation (G607S) in the endothelin-converting enzyme-like 1 (ECEL1) gene in a consanguineous pedigree of Turkish origin presenting with a syndrome of camptodactyly, scoliosis, limited knee flexion, significant refractive errors and ophthalmoplegia. ECEL1 mutations were recently reported to cause recessive forms of distal arthrogryposis. This report expands on the molecular basis and the phenotypic spectrum of ECEL1-associated congenital contracture syndromes.

Comparison of cognitive function after carotid artery stenting versus carotid endarterectomy.

The effect of carotid artery stenting (CAS) and carotid endarterectomy (CEA) on cognitive function is unclear. Both cognitive improvement and decline have been reported after CAS and CEA. We aimed to compare the changes in postprocedural cognitive function after CAS versus CEA. A systematic qualitative review of the literature was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement for studies evaluating the changes in cognitive function after CAS compared with CEA. Thirteen studies (403 CEAs; 368 CAS procedures) comparing the changes in cognitive function after CEA versus CAS were identified. Most studies did not show significant differences in overall cognitive function or only showed a difference in a single cognitive test between the two procedures. A definitive conclusion regarding the effect of CAS versus CEA on cognitive function was not possible owing to heterogeneity in definition, method, timing of assessment, and type of cognitive tests. For the same reasons, performing a meta-analysis was not feasible. The lack of standardization of specific cognitive tests and timing of assessment of cognitive function after CAS and CEA do not allow for definite conclusions to be drawn. Larger, adequately-powered and appropriately designed studies are required to accurately evaluate the effect of CAS versus CEA on postprocedural cognitive function.

Identification of a gene set to evaluate the potential effects of loud sounds from seismic surveys on the ears of fishes: a study with Salmo salar.

Functional genomic studies were carried out on the inner ear of Atlantic salmon Salmo salar following exposure to a seismic airgun. Microarray analyses revealed 79 unique transcripts (passing background threshold), with 42 reproducibly up-regulated and 37 reproducibly down-regulated in exposed v. control fish. Regarding the potential effects on cellular energetics and cellular respiration, altered transcripts included those with roles in oxygen transport, the glycolytic pathway, the Krebs cycle and the electron transport chain. Of these, a number of transcripts encoding haemoglobins that are important in oxygen transport were up-regulated and among the most highly expressed. Up-regulation of transcripts encoding nicotinamide riboside kinase 2, which is also important in energy production and linked to nerve cell damage, points to evidence of neuronal damage in the ear following noise exposure. Transcripts related to protein modification or degradation also indicated potential damaging effects of sound on ear tissues. Notable in this regard were transcripts associated with the proteasome-ubiquitin pathway, which is involved in protein degradation, with the transcript encoding ubiquitin family domain-containing protein 1 displaying the highest response to exposure. The differential expression of transcripts observed for some immune responses could potentially be linked to the rupture of cell membranes. Meanwhile, the altered expression of transcripts for cytoskeletal proteins that contribute to the structural integrity of the inner ear could point to repair or regeneration of ear tissues including auditory hair cells. Regarding potential effects on hormones and vitamins, the protein carrier for thyroxine and retinol (vitamin A), namely transthyretin, was altered at the transcript expression level and it has been suggested from studies in mammalian systems that retinoic acid may play a role in the regeneration of damaged hair cells. The microarray experiment identified the transcript encoding growth hormone I as up-regulated by loud sound, supporting previous evidence linking growth hormone to hair cell regeneration in fishes. Quantitative (q) reverse transcription (RT) polymerase chain reaction (qRT-PCR) analyses confirmed dysregulation of some microarray-identified transcripts and in some cases revealed a high level of biological variability in the exposed group. These results support the potential utility of molecular biomarkers to evaluate the effect of seismic surveys on fishes with studies on the ears being placed in a priority category for development of exposure-response relationships. Knowledge of such relationships is necessary for addressing the question of potential size of injury zones.

Improving the capacity of researchers and bereaved parents to co-design and translate stillbirth research together.

BACKGROUND: Working with bereaved parents in co-designed stillbirth research, policy and practice is essential to improving care and outcomes. PROBLEM: Effective parent engagement is often lacking. This may be due to bereaved parents not feeling adequately and appropriately supported to be involved. AIM: To consult bereaved parents with the aim to understand their experiences, attitudes, and needs around involvement in stillbirth research and gain feedback about the usefulness and appropriateness of a proposed co-designed guide to support their involvement, including content and design aspects of this resource. METHODS: An online co-designed survey was disseminated via Australian parent support organisations social media in August 2022. FINDINGS: All 90 respondents were bereaved parents, 94% (n = 85) were female. Two-thirds (67%, n = 60) had never participated in stillbirth research, 80% (n = 72) agreed involvement of bereaved parents in research was important or extremely important and 81% (n = 73) were interested in future research involvement. Common motivations for involvement were wanting to leave a legacy for their baby and knowing research outcomes. Common barriers included not having been asked to participate or not knowing how. Most (89%, n = 80) agreed the proposed guide would be useful. Highly valued topics were the importance of bereaved parents' voices in stillbirth research and how they can make a difference. CONCLUSION: The majority of bereaved parents we surveyed want to be involved in stillbirth research and would value a resource to support this. The proposed concept and content for a co-designed guide to aid engagement was well supported.

Prevalence of Plastic and Hardware Foreign Bodies among Goats at Malawi Markets.

Smallholder goat production plays a major role in rural livelihoods and food security in Malawi, but suffers from drastic and unpredictable production losses. While goat production is closely linked to small-scale local markets for slaughter and butchering, the perspectives of butchers and their potential as a source of animal health information are largely untapped. Butchers can provide insights into goat health status at slaughter as well as issues that go unseen before slaughter, such as the presence of indigestible foreign bodies (IFBs). IFBs include solid materials such as plastics and hardware (metals, stones, and other hard objects) that cause foreign body syndrome and can lead to impaction, oedema, malnutrition, and death. To estimate the presence of IFBs, 150 market stand butchers were surveyed across five districts in Malawi, focusing on a distinction between hardware and single-use plastics, which are still widely present in Malawi despite bans on production. Most butchers found plastic IFBs (80.7%), with over half (56.7%) reporting plastic IFBs recently among the past five slaughters. Hardware IFBs were less common, reported by 45.3% of butchers. While some butchers commented on the impact of IFBs on meat quality metrics ex-post, the majority observed no differences. While butchers unanimously considered health to be an important characteristic when sourcing goats, 70.7% consider injury status to be less important or not important. Overall, this study highlights the issue of anthropogenic waste pollution on goat production in Malawi and demonstrates the potential for the surveillance of goat health at market.

Gamma radiation-induced nanodefects in diffusive memristors and artificial neurons.

Gamma photons with an average energy of 1.25 MeV are well-known to generate large amounts of defects in semiconductor electronic devices. Here we investigate the novel effect of gamma radiation on diffusive memristors based on metallic silver nanoparticles dispersed in a dielectric matrix of silica. Our experimental findings show that after exposure to radiation, the memristors and artificial neurons made of them demonstrate much better performance in terms of stable volatile resistive switching and higher spiking frequencies, respectively, compared to the pristine samples. At the same time we observe partial oxidation of silver and reduction of silicon within the switching silica layer. We propose nanoinclusions of reduced silicon distributed across the silica layer to be the backbone for metallic nanoparticles to form conductive filaments, as supported by our theoretical simulations of radiation-induced changes in the diffusion process. Our findings propose a new opportunity to engineer the required characteristics of diffusive memristors in order to emulate biological neurons and develop bio-inspired computational technology.

Post-hatching parental care masks the effects of egg size on offspring fitness: a removal experiment on burying beetles.

Parents can increase the fitness of their offspring by allocating nutrients to eggs and/or providing care for eggs and offspring. Although we have a good understanding of the adaptive significance of both egg size and parental care, remarkably little is known about the co-evolution of these two mechanisms for increasing offspring fitness. Here, we report a parental removal experiment on the burying beetle Nicrophorus vespilloides in which we test whether post-hatching parental care masks the effect of egg size on offspring fitness. As predicted, we found that the parent's presence or absence had a strong main effect on larval body mass, whereas there was no detectable effect of egg size. Furthermore, egg size had a strong and positive effect on offspring body mass in the parent's absence, whereas it had no effect on offspring body mass in the parent's presence. These results support the suggestion that the stronger effect of post-hatching parental care on offspring growth masks the weaker effect of egg size. We found no correlation between the number and size of eggs. However, there was a negative correlation between larval body mass and brood size in the parent's presence, but not in its absence. These findings suggest that the trade-off between number and size of offspring is shifted from the egg stage towards the end of the parental care period and that post-hatching parental care somehow moderates this trade-off.

Australian women's perceptions and practice of sleep position in late pregnancy: An online survey.

BACKGROUND: Going-to-sleep in the supine position in later pregnancy (≥28 weeks) has been identified as a risk factor for stillbirth. Internationally, public awareness campaigns have been undertaken encouraging women to sleep on their side during late pregnancy. AIM: This study aimed to identify sleep practices, attitudes and knowledge in pregnant women, to inform an Australian safe sleeping campaign. METHODS: A web-based survey of pregnant women ≥28 weeks' gestation conducted from November 2017 to January 2018. The survey was adapted from international sleep surveys and disseminated via pregnancy websites and social media platforms. FINDINGS: Three hundred and fifty-two women participated. Five (1.6%) reported going to sleep in the supine position. Most (87.8%) had received information on the importance of side-sleeping in pregnancy. Information was received from a variety of sources including maternity care providers (186; 66.2%) and the internet (177; 63.0%). Women were more likely to report going to sleep on their side if they had received advice to do so (OR 2.3; 95% CI 1.0-5.1). Thirteen (10.8%) reported receiving unsafe advice, including changing their going-to-sleep position to the supine position. DISCUSSION: This indicates high level awareness and practice of safe late-pregnancy going-to-sleep position in participants. Opportunities remain for improvement in the information provided, and understanding needs of specific groups including Aboriginal and Torres Strait Islander women. CONCLUSION: Findings suggest Australian women understand the importance of sleeping position in late pregnancy. Inconsistencies in information provided remain and may be addressed through public awareness campaigns targeting women and their care providers.

Gastrointestinal symptoms in Parkinson disease: clinical aspects and management.

Although it is now generally recognized that the clinical spectrum of Parkinson disease (PD) is broader than its defining motor aspects, its various non-motor symptoms are often not routinely assessed in the clinical setting. As most of these symptoms are amenable to treatment, improved recognition would lead to more comprehensive management of the disease, and ultimately improve the quality of life for PD patients. In an attempt to increase the general awareness of physicians caring for these patients, this article focuses on the clinical manifestations and treatment of the gastrointestinal symptoms most commonly experienced by PD patients, as well as on the gastrointestinal side effects of antiparkinsonian treatments.

Emotional distress and health risk behaviours of mothers of United States Marines.

AIM: The aim was to explore emotional distress and health risk behaviours of mothers of servicemen. The study was inspired by the first author's clinical practice in primary care among women who reported significant emotional distress surrounding impending deployment of their sons. BACKGROUND: Thousands of US service members have been deployed in the current wars. The potentially profound effects of deployment on emotional distress of military spouses and children have been documented; however, mothers of servicemen have not been studied. METHODS: This was an exploratory descriptive study to determine self-reported levels of emotional distress and health risk behaviours in the mothers of deployed male US Marines compared with mothers of male Marines not currently deployed. Mothers were accessed via a voluntary online support organization. RESULTS: Mothers of deployed sons reported significantly higher levels of emotional distress and more health risk behaviours compared with mothers of sons not deployed. Many of the mothers in both groups reported high levels of emotional distress. DISCUSSION: As primary care providers, nurses should be alert to the high levels of emotional distress and health risk behaviours among all patients. This exploratory study highlights these dimensions in mothers of servicemen. CONCLUSIONS: This study is the first of mothers of sons serving in the military. While the focus is on mothers of sons serving in the US military, their experience is likely not unique. Mothers of military service members all over the world send their children off to war and wait for their safe return.

Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope.

Virus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity to many virus infections. It has recently been shown that CTL are detectable early during primary infection with the primate lentiviruses, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To better characterize the CTL response during acute HIV-1 infection, HIV-1-specific CTL clones were generated from two patients during symptomatic HIV-1 seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restricted clones from the same individual were found to have differing virus strain specificities. Both clones recognized the 11-amino acid peptide RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at position 779 in this epitope abrogated lysis by one clone but not the other. A CTL clone from the other patient, restricted by a different class I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI from position 769-777 of gp41. Of note, the peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1. Autologous virus sequences from seroconversion and up to 15 wk after presentation in these two patients were recognized by the CTL clones isolated during acute infection. None of the CTL clones recognized the MN strain of HIV-1, indicating the problems inherent in relying on a single virus strain in the development of a vaccine. These studies have identified an immunodominant and promiscuous area for the generation of CTL responses within gp41. This recognition of autologous virus sequences by the initial CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response is involved in the initial control of that virus. These studies indicate the importance of the CTL response to HIV-1 infection and have implications in the design of vaccines.