Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

<p>Abstract</p> <p>Background</p> <p>A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (<it>Ovis canadensis</it>) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA.</p> <p>Results</p> <p>Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus.</p> <p>Conclusions</p> <p>Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.</p

Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-beta1 and bax genes

BACKGROUND: Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. METHODS: Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. RESULTS: Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05). CONCLUSION: An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium

Lymphadenectomy during pulmonary metastasectomy: Impact on survival and recurrence

Background and Objectives: Lymphadenectomy during pulmonary metastasectomy (PM) is widely carried out. We assessed the potential benefit on patient survival and tumor recurrence of this practice. Methods: One hundred eighty‐one patients undergoing a first PM were studied. Eighty‐six patients (47.5%) underwent lymphadenectomy (L+ group) whereas 95 (52.5%) did not undergo nodal harvesting (L−group). Main outcomes were overall survival (OS) and disease‐free survival (DFS). Median follow‐up was 25 months (interquartile range [IQR], 13‐49). Results: At follow‐up 84 patients (46.4%) died, whereas 97 (53.6%) were still alive with recurrence in 78 patients (43%). There was no difference in 5‐year survival (L+ 30.0% vs L− 43.2%; P = .87) or in the 5‐year cumulative incidence of recurrence (L + 63.2% vs L−80%; P = .07) between the two groups. Multivariable analysis indicated that disease‐free interval (DFI) less than 29 months (P P = .003) were significant predictors of death. Metastases from non‐small–cell lung cancer increased the risk of lung comorbidities by a factor of 19.8, whereas the risk of DFI less than 29 months was increased nearly 11‐fold. Competing risk regression identified multiple metastases (P = .004), head/neck primary tumor (P = .009), and age less than 67 years (P = .024) as independent risk factors for recurrence. Conclusion: Associated lymphadenectomy showed not to give any additional advantage in terms of survival and recurrence after PM

"Practical Knowledge" and Perceptions of Antibiotics and Antibiotic Resistance Among Drugsellers in Tanzanian Private Drugstores.

Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85%) said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic resistance based on practical experience. The drugsellers have considerable "practical knowledge" of antibiotics and a perception of antibiotic resistance based on practical experience. In the process of upgrading private drugstores and formalizing the sale of antibiotics from these outlets in resource-constrained settings, their "practical knowledge" as well as their perceptions must be taken into account in order to attain rational dispensing practices

Papillary muscle intervention vs mitral ring annuloplasty in ischemic mitral regurgitation

Background and Aims The main pathophysiological factor of chronic ischemic mitral regurgitation (MR) is the outward displacement of the papillary muscles (PMs) leading to leaflet tethering. For this reason, papillary muscle intervention (PMI) in combination with mitral ring annuloplasty (MRA) has recently been introduced into clinical practice to correct this displacement, and to reduce the recurrence of regurgitation. Methods A meta‐analysis was conducted comparing the outcomes of PMI and MRA performed in combination vs MRA performed alone, in terms of MR recurrence and left ventricular reverse remodeling (LVRR). A meta‐regression was carried out to investigate the impact of the type of PMI procedure on the outcomes. Results MR recurrence in patients undergoing both PMI and MRA was lower than in those who only had MRA (log incidence rate ratio, −0.66; lower‐upper limits, −1.13 to 0.20; I2 = 0.0%; p = .44; Egger's test: intercept 0.35 [−0.78 to 1.51]; p = .42). The group with both PMI and MRA and that with only MRA showed a slightly higher reduction in left ventricular diameters (−5.94%; −8.75% to 3.13%,). However, in both groups, LVRR was p = .33). Conclusions Using PMI and MRA together has a lower MR recurrence than using MRA alone. No significant LVRR was observed between the two groups nor between the PMI techniques employed

PAPER Baby steps: investigating the development of perceptual-motor couplings in infancy

Abstract There are cells in our motor cortex that fire both when we perform and when we observe similar actions. It has been suggested that these perceptual-motor couplings in the brain develop through associative learning during correlated sensorimotor experience. Although studies with adult participants have provided support for this hypothesis, there is no direct evidence that associative learning also underlies the initial formation of perceptual-motor couplings in the developing brain. With the present study we addressed this question by manipulating infants&apos; opportunities to associate the visual and motor representation of a novel action, and by investigating how this influenced their sensorimotor cortex activation when they observed this action performed by others. Pre-walking 7-9-month-old infants performed stepping movements on an infant treadmill while they either observed their own real-time leg movements (Contingent group) or the previously recorded leg movements of another infant (Non-contingent control group). Infants in a second control group did not perform any steps and only received visual experience with the stepping actions. Before and after the training period we measured infants&apos; sensorimotor alpha suppression, as an index of sensorimotor cortex activation, while they watched videos of other infants&apos; stepping actions. While we did not find greater sensorimotor alpha suppression following training in the Contingent group as a whole, we nevertheless found that the strength of the visuomotor contingency experienced during training predicted the amount of sensorimotor alpha suppression at post-test in this group. We did not find any effects of motor experience alone. These results suggest that the development of perceptual-motor couplings in the infant brain is likely to be supported by associative learning during correlated visuomotor experience. Research highlights • Two decades after the discovery of mirror neurons, the mechanisms underlying their ontogeny remain relatively unknown. • It has been suggested that these perceptual-motor couplings in the brain develop through associative learning during correlated sensorimotor experience. • To test this hypothesis we manipulated infants&apos; opportunities to associate the visual and motor representation of a novel action, and investigated how this influenced their sensorimotor cortex activation during action observation. • Our results show that correlated visuomotor experience predicts sensorimotor cortex activation during action observation

Remote home monitoring (virtual wards) for confirmed or suspected COVID-19 patients:a rapid systematic review

Background: the aim of this review was to analyze the implementation and impact of remote home monitoring models (virtual wards) for confirmed or suspected COVID-19 patients, identifying their main components, processes of implementation, target patient populations, impact on outcomes, costs and lessons learnt. Methods: we carried out a rapid systematic review on models led by primary and secondary care across seven countries (US, Australia, Canada, The Netherlands, Ireland, China, UK). The main outcomes included in the review were: impact of remote home monitoring on virtual length of stay, escalation, emergency department attendance/reattendance, admission/readmission and mortality. The search was updated on February 2021. We used the PRISMA statement and the review was registered on PROSPERO (CRD: 42020202888). Findings: the review included 27 articles. The aim of the models was to maintain patients safe in the appropriate setting. Most models were led by secondary care and confirmation of COVID-19 was not required (in most cases). Monitoring was carried via online platforms, paper-based systems with telephone calls or (less frequently) through wearable sensors. Models based on phone calls were considered more inclusive. Patient/career training was identified as a determining factor of success. We could not reach substantive conclusions regarding patient safety and the identification of early deterioration due to lack of standardized reporting and missing data. Economic analysis was not reported for most of the models and did not go beyond reporting resources used and the amount spent per patient monitored. Interpretation: future research should focus on staff and patient experiences of care and inequalities in patients' access to care. Attention needs to be paid to the cost-effectiveness of the models and their sustainability, evaluation of their impact on patient outcomes by using comparators, and the use of risk-stratification tools

Patient and staff experiences of using technology-enabled and analogue models of remote home monitoring for COVID-19 in England: A mixed-method evaluation

Objective: To evaluate patient and staff experiences of using technology-enabled (‘tech-enabled’) and analogue remote home monitoring models for COVID-19, implemented in England during the pandemic. // Methods: Twenty-eight sites were selected for diversity in a range of criteria (e.g. pre-hospital or early discharge service, mode of patient data submission). Between February and May 2021, we conducted quantitative surveys with patients, carers and staff delivering the service, and interviewed patients, carers, and staff from 17 of the 28 services. Quantitative data were analysed using descriptive statistics and both univariate and multivariate analyses. Qualitative data were interpreted using thematic analysis. // Results: Twenty-one sites adopted mixed models whereby patients could submit their symptoms using either tech-enabled (app, weblink, or automated phone calls) or analogue (phone calls with a health professional) options; seven sites offered analogue-only data submission (phone calls or face-to-face visits with a health professional). Sixty-two patients and carers were interviewed, and 1069 survey responses were received (18 % response rate). Fifty-eight staff were interviewed, and 292 survey responses were received (39 % response rate). Patients who used tech-enabled modes tended to be younger (p = 0.005), have a higher level of education (p = 0.011), and more likely to identify as White British (p = 0.043). Most patients found relaying symptoms easy, regardless of modality, though many received assistance from family or friends. Staff considered the adoption of mixed delivery models beneficial, enabling them to manage large patient numbers and contact patients for further assessment as needed; however, they suggested improvements to the functionality of systems to better fit clinical and operational needs. Human contact was important in all remote home monitoring options. // Conclusions: Organisations implementing tech-enabled remote home monitoring at scale should consider adopting mixed models which can accommodate patients with different needs; focus on the usability and interoperability of tech-enabled platforms; and encourage digital inclusivity for patients

A rapid mixed-methods evaluation of remote home monitoring models during the COVID-19 pandemic in England

BACKGROUND: Remote home monitoring services were developed and implemented for patients with COVID-19 during the pandemic. Patients monitored blood oxygen saturation and other readings (e.g. temperature) at home and were escalated as necessary. OBJECTIVE: To evaluate effectiveness, costs, implementation, and staff and patient experiences (including disparities and mode) of COVID-19 remote home monitoring services in England during the COVID-19 pandemic (waves 1 and 2). METHODS: A rapid mixed-methods evaluation, conducted in two phases. Phase 1 (July-August 2020) comprised a rapid systematic review, implementation and economic analysis study (in eight sites). Phase 2 (January-June 2021) comprised a large-scale, multisite, mixed-methods study of effectiveness, costs, implementation and patient/staff experience, using national data sets, surveys (28 sites) and interviews (17 sites). RESULTS: Phase 1 Findings from the review and empirical study indicated that these services have been implemented worldwide and vary substantially. Empirical findings highlighted that communication, appropriate information and multiple modes of monitoring facilitated implementation; barriers included unclear referral processes, workforce availability and lack of administrative support. Phase 2 We received surveys from 292 staff (39% response rate) and 1069 patients/carers (18% response rate). We conducted interviews with 58 staff, 62 patients/carers and 5 national leads. Despite national roll-out, enrolment to services was lower than expected (average enrolment across 37 clinical commissioning groups judged to have completed data was 8.7%). There was large variability in implementation of services, influenced by patient (e.g. local population needs), workforce (e.g. workload), organisational (e.g. collaboration) and resource (e.g. software) factors. We found that for every 10% increase in enrolment to the programme, mortality was reduced by 2% (95% confidence interval: 4% reduction to 1% increase), admissions increased by 3% (-1% to 7%), in-hospital mortality fell by 3% (-8% to 3%) and lengths of stay increased by 1.8% (-1.2% to 4.9%). None of these results are statistically significant. We found slightly longer hospital lengths of stay associated with virtual ward services (adjusted incidence rate ratio 1.05, 95% confidence interval 1.01 to 1.09), and no statistically significant impact on subsequent COVID-19 readmissions (adjusted odds ratio 0.95, 95% confidence interval 0.89 to 1.02). Low patient enrolment rates and incomplete data may have affected chances of detecting possible impact. The mean running cost per patient varied for different types of service and mode; and was driven by the number and grade of staff. Staff, patients and carers generally reported positive experiences of services. Services were easy to deliver but staff needed additional training. Staff knowledge/confidence, NHS resources/workload, dynamics between multidisciplinary team members and patients' engagement with the service (e.g. using the oximeter to record and submit readings) influenced delivery. Patients and carers felt services and human contact received reassured them and were easy to engage with. Engagement was conditional on patient, support, resource and service factors. Many sites designed services to suit the needs of their local population. Despite adaptations, disparities were reported across some patient groups. For example, older adults and patients from ethnic minorities reported more difficulties engaging with the service. Tech-enabled models helped to manage large patient groups but did not completely replace phone calls. LIMITATIONS: Limitations included data completeness, inability to link data on service use to outcomes at a patient level, low survey response rates and under-representation of some patient groups. FUTURE WORK: Further research should consider the long-term impact and cost-effectiveness of these services and the appropriateness of different models for different groups of patients. CONCLUSIONS: We were not able to find quantitative evidence that COVID-19 remote home monitoring services have been effective. However, low enrolment rates, incomplete data and varied implementation reduced our chances of detecting any impact that may have existed. While services were viewed positively by staff and patients, barriers to implementation, delivery and engagement should be considered. STUDY REGISTRATION: This study is registered with the ISRCTN (14962466). FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (RSET: 16/138/17; BRACE: 16/138/31) and NHSEI and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 13. See the NIHR Journals Library website for further project information. The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care