Subtelomeric plasticity contributes to gene family expansion in the human parasitic flatworm Schistosoma mansoni.

BACKGROUND: The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle. RESULTS: Using the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument-the tissue located at the host-parasite physical interface-of intramolluscan life stages. CONCLUSIONS: We propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Molecular autopsy for fetal structural anomaly: diagnostic and clinical utility of multidisciplinary team approach.

OBJECTIVES: In the West Midlands Regional Genetic Service, cases of perinatal death with a possible genetic diagnosis are evaluated by the Perinatal Pathology Genetic Multidisciplinary Team (MDT). The MDT assessed autopsy findings and considered genomic assessments. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT. This is the first evaluation since the introduction of whole genome and whole exome sequencing in routine clinical care. METHOD: The outcomes for all the perinatal MDT cases from January 2021 to December 2021 were examined. All cases received a full or partial post-mortem examination (PM) and a chromosomal microarray. Demographics, phenotype, MDT recommendations, genetic testing, diagnoses, outcomes, impact of PM and impact of genetic testing were collected from patient case notes. RESULTS: One hundred and twenty-three cases were discussed at the MDT meeting in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were identified in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) of all cases or 45% (29/64) of the cases with a suspected genetic diagnosis who underwent genetic testing. PM examination added clinically actionable phenotype data in 79% of cases. A genetic diagnosis enabled accurate counselling of recurrence risk and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions. CONCLUSIONS: Genomic testing was a clinically useful addition to (but not a substitute for) PM examination in perinatal cases associated with structural anomalies. The MDT model helped assess cases and plan appropriate follow-up. Expedited whole genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand prenatal phenotypes and detect novel disease genes and should be a priority for future research. This article is protected by copyright. All rights reserved.

Producer perceptions of dairy calf management, behavior, and welfare.

Approaches for raising calves vary across commercial dairy farms and relate to behavioral opportunities and animal welfare. The objectives of this study were to evaluate how US dairy producers and calf managers perceive (1) the welfare implications of varying management practices (including social housing and milk allowance) and behaviors in dairy calves, and (2) aspects of the human-animal relationship in calf rearing and relationships with on-farm management and personal calf handling habits. Survey questions were primarily quantitative (e.g., Likert scales) and addressed how common calf management practices and observed calf behaviors were related to aspects of welfare, including calf health and comfort. We additionally posed questions addressing respondent habits, management protocols, and perceptions related to human-animal interaction. Responses from 93 dairy producers and calf managers were collected via digital surveys. Social housing was viewed as being generally positive for both calf comfort and health, although this view was stronger with respect to calf comfort. Respondents from farms using social housing (56%) had more positive perceptions of social housing, viewed social play as being associated with better calf comfort and health, and considered access to other calves and "freedom to express natural behavior" as being more important for calves, compared with respondents from farms not providing social housing. Providing greater milk allowances (>7.6 L/d) was viewed as being good for both calf comfort and health, although respondents from farms providing these milk allowances (59%) had more positive perceptions than those who provided lesser allowances. Abnormal oral behaviors were viewed as being associated with both poor calf comfort and health. The welfare importance of various resources which may reduce abnormal oral behaviors (including hay and brushes) was perceived more ambiguously, although respondents from farms providing these resources, compared with those who do not, generally viewed them as more preferred by calves. We observed a positive relationship between how respondents perceived the human-animal bond (i.e., that calves enjoy contact with humans) and stated personal behavior related to calf contact (frequency of contacting calves to scratch or pet them). Respondent demographics were not related to perceptions of the human-animal relationship, but respondents identifying as female described more frequent positive calf interactions. Described aspects of human-animal interactions were not related to implementation of social housing on-farm. Job satisfaction was positively related to perception of the human-animal relationship. Overall, these results suggest that most calf management personnel place a high value on calf welfare, although farms implementing social housing appear to place a greater value on subjective calf well-being, and individual perceptions of animal welfare may depend on practical experience.

Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: cohort study.

OBJECTIVES: To determine (1) the diagnostic yield and turnaround time (TAT) of two consecutive prenatal exome sequencing (ES) pathways, (2) the evolution of the fetal phenotype and (3) the clinical impact of detecting causative pathogenic variants and incidental findings. METHODS: This was a retrospective cohort analysis of prospectively collected fetal cases that underwent trio ES in the presence of a structural anomaly and normal chromosomal microarray testing in the West Midlands Regional Genetics Laboratory, Birmingham, UK. The study included two phases: (1) between July 2018 and October 2020, the clinical pathway from the Prenatal Assessment of Genomes and Exomes (PAGE) study was adopted and involved prenatal trio ES based on a panel of 1542 development disorder genes and case selection by a multidisciplinary team; (2) between October 2020 and July 2021, prenatal trio ES investigation was based on the National Health Service (NHS) England R21 pathway, with definitive inclusion criteria and a panel of 1205 prenatally relevant genes. Deep phenotyping was performed throughout pregnancy and postnatally. RESULTS: A total of 54 cases were included. The diagnostic yield before vs after R21 pathway implementation was 28.0% (7/25) and 55.2% (16/29), respectively (P = 0.04). The respective values for mean TAT were 54.0 days (range, 14-213 days) and 14.2 days (range, 3-29 days). In cases in which a causative pathogenic variant was identified and in which the pregnancy reached the third trimester, additional anomalies were detected between the second and third trimesters in 73.3% (11/15) of cases, predominantly secondary to progressive hydropic features (3/11 (27.3%)), arthrogryposis (3/11 (27.3%)) or brain anomaly (2/11 (18.2%)). In three cases, a variant of uncertain significance was reclassified to likely pathogenic based on postnatal information. Detection of a causative pathogenic variant had a significant clinical impact in 78.3% (18/23) of cases, most frequently affecting decision-making regarding the course of the pregnancy and neonatal management (7/18 (38.9%)). CONCLUSIONS: Prenatal ES using the NHS England R21 pathway showed great promise when applied to this cohort, allowing a genetic diagnosis to be made in over half of preselected cases with a fetal structural anomaly on ultrasound. Monitoring and real-time updating of fetal phenotype and reclassification of variants based on postnatal findings is vital to increase the clinical impact that is already evident from this emerging genomic technology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Development of human-directed behavior in dairy calves reared individually or in pairs.

Although social contact between dairy calves has broad effects on their behavioral development, influences of calf social housing on human-animal relationships are less well understood, despite implications for longer-term calf management and welfare. We characterized human-animal interactions in 3 distinct testing contexts to examine effects of social housing on development of human-directed behavior. At birth, Holstein heifer calves were randomly assigned to individual housing (n = 17 calves) or pair housing (n = 17 calves; 1 focal calf/pair). A human approach test was performed twice in the home pen (wk 3 and 5 of life), within an open testing arena (13 × 7 m; wk 4 of life), and within group-housing pens 6 d after all calves were weaned, mingled between treatments, and moved to groups (4 calves/pen; wk 8 of life). For these tests, a human approached, and then extended their hand, over a 2 min period for home and group pen tests and a 5 min period for the arena test, and behavior was recorded from video. During preweaning human approach tests in the home pen, individually housed calves had shorter latencies to contact the human (22.4 vs. 45.1 s; individual vs. pair housing) and spent more time in contact with the human [80.5 vs. 41.1 s; standard error (SE) = 9.9; individual vs. pair housing], with similar responses between repeated tests. In the arena approach test, individually housed calves spent more time oriented toward the human (134.6 vs. 81.3 s; SE = 16.5; individual vs. pair housing), whereas pair-housed calves were more likely to perform pen-directed non-nutritive oral behavior (60 vs. 40% of calves; pair vs. individual housing), suggesting differences in interest directed toward the human compared with the novel environment. We also found that total duration of human contact was correlated between the first home pen approach test and the novel arena test, but that specific response to human approach varied between testing contexts. Effects of treatment persisted during the postweaning group pen approach test, with previously individually housed calves tending to spend more time looking toward the human (53.0 vs. 30.0 s; SE = 9.4; individual vs. pair housing) and more likely to contact the human (47 vs. 12% of calves; individual vs. pair housing). Overall, these results show persistent effects of early life social housing on human-directed behavior which may have implications for longer-term management.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer.

BACKGROUND: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. METHODS: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. RESULTS: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P < 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047). CONCLUSION: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention.

Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04-6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.

Effect of preoperative inspiratory muscle training on physical functioning following esophagectomy.

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer.

PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.

Effects of glyphosate formulations on the population dynamics of two freshwater cladoceran species.

The general objective of this work is to experimentally assess the effects of acute glyphosate pollution on two freshwater cladoceran species (Daphnia magna and Ceriodaphnia dubia) and to use this information to predict the population dynamics and the potential for recovery of exposed organisms. Five to six concentrations of four formulations of glyphosate (4-Gly) (Eskoba®, Panzer Gold®, Roundup Ultramax® and Sulfosato Touchdown®) were evaluated in both cladoceran species through acute tests and 15-day recovery tests in order to estimate the population dynamics of microcrustaceans. The endpoints of the recovery test were: survival, growth (number of molts), fecundity, and the intrinsic population growth rate (r). A matrix population model (MPM) was applied to r of the survivor individuals of the acute tests, followed by a Monte Carlo simulation study. Among the 4-Gly tested, Sulfosato Touchdown® was the one that showed higher toxicity, and C. dubia was the most sensitive species. The Monte Carlo simulation study showed an average value of λ always <1 for D. magna, indicating that its populations would not be able to survive under natural environmental conditions after an acute Gly exposure between 0.25 and 35 a.e. mg L-1. The average value of λ for C. dubia was also <1 after exposure to Roundup Ultramax®: 1.30 and 1.20 for 1.21 and 2.5 mg a.e. L-1,respectively. The combined methodology-recovery tests and the later analysis through MPM with a Monte Carlo simulation study-is proposed to integrate key demographic parameters and predict the possible fate of microcrustacean populations after being exposed to acute 4-Gly contamination events.

An assessment of Irish farmers' knowledge of the risk of spread of infection from animals to humans and their transmission prevention practices.

The aim of this study was to ascertain farmers' knowledge of the risk of spread of infection from animals to humans, and their transmission prevention practices. This was a survey of farmers who submitted material to Ireland's Regional Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers). Ninety per cent of farmers were not aware that infection can be acquired from apparently healthy animals. Over half were not aware that disease could be contracted from sick poultry or pets. Conversely, the knowledge of the risk to pregnant women of infection from birthing animals was high (88%). Four-fifths of farmers sourced drinking water from a private well, and of these, 62% tested their water less frequently than once a year. Of dairy farmers, 39% drank unpasteurised milk once a week or more frequently. Veterinarians were the most commonly cited information source for diseases on farms. The survey findings indicate that the level of farmers' knowledge and awareness of the spread of infection from animals to humans is a concern. Further education of the farming community is needed to increase awareness of both the potential biohazards present on farms and the practical measures that can be taken to mitigate the risk of zoonoses.

Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study.

Reduced physical functioning is common following resections for esophageal cancer; however, objective data on physical performance outcomes in this cohort are rare. The aim of this study was to assess the physical performance and health related quality of life (HRQOL) of disease free survivors and compare findings in a case matched noncancer control group. Twenty-five males (mean (±SD) aged 63 (±6) years) who were over 6 months postesophagectomy and disease-free were compared with 25 controls (60 ± 6 years). Physical functioning was assessed through hand grip strength (dynamometry), exercise capacity (incremental shuttle walk test), physical activity levels (RT3 accelerometer), and body composition (bio-electrical impedance analysis). Health-related quality of life was measured using the EORTC QLQ-C30 questionnaire. Esophageal cancer survivors demonstrated significantly lower fitness (P < 0.001) and time spent in moderate (P < 0.001) and vigorous (P < 0.001) intensity physical activity compared with controls. Global health status and quality of life were similar in both groups (P = 0.245); however, physical and role functioning domains were lower in the cancer survivors (P < 0.001, and P = 0.001, respectively). These data show that disease-free survivors of curative esophageal cancer treatment demonstrate a significant compromise in physical functioning compared with controls, thus highlighting the multiple, complex rehabilitative needs of this cohort.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-ß, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P < 0.05). Higher postoperative circulating levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal.

Impact of supplemental home enteral feeding postesophagectomy on nutrition, body composition, quality of life, and patient satisfaction.

The aim of this prospective cohort study is to analyze the impact of supplemental home enteral nutrition (HEN) post-esophageal cancer surgery on nutritional parameters, quality of life (QL), and patient satisfaction. A systematic review reported that over 60% of patients lose >10% of both body weight and BMI by 6 months after esophagectomy. Enteral feeding (EF) is increasingly a modern standard postoperatively; however, the impact of extended HEN postdischarge has not been systematically studied. One hundred forty-nine consecutive patients [mean age 62 ± 9, 80% male,76% adenocarcinoma, 66% on multimodal protocols, and 69% with BMI ≥ 25 kg/m2] were studied. Jejunal EF commenced day 1 postoperatively, and supplemental overnight HEN (764 kcal; 32g protein) continued on discharge for a planned further 4 weeks. Weight, BMI, and body composition analysis (bioimpedance analysis) were measured at baseline, preoperatively and at 1, 3, and 6 months, along with the EORTC QLQ-C30/OES18 QL measures. A patient satisfaction questionnaire addressed eight key items in relation to HEN (max score 100/item). Median (range) total duration of EF was 49 days (28-96). Overall compliance was 96%. At 6 months, compared with preoperatively, 58 (39%) patients lost >10% weight, with median (IQR) loss of 6.8 (4-9) kg, and 62 (41%) patients lost >10% BMI. Lean body mass and body fat were significantly (p < 0.001) decreased. Mean global QL decreased (p < 0.01) from 82 to 72. A high mean satisfaction score (>70 ± 11/100) was reported, >80 for practical training, activities of daily living, pain, anxiety, recovery and impact on caregivers, with lower scores for appetite (33 ± 24) and sleep (63 ± 30). Supplemental HEN for a minimum of one month postdischarge is associated with high compliance and patient satisfaction. Weight and BMI loss may still be substantial, however this may be less than published literature, in addition the impact on HR-QL may be attenuated. HEN has both subjective and objective rationale and merits further validation toward optimizing nutritional recovery and overall wellbeing.