bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute clouding of a trifocal intraocular lens with spontaneous resolution: a case report
Authors: Zhang Tao , Li Shaowei , Liu Chang , Zhao Ruihua , Chang Chenghe , Han Na
Published: October 2019

Background

Opacification of hydrophobic and hydrophilic intraocular lenses (IOLs) has been reported. Herein, we report a case of spontaneous resolution of opacification following acute clouding of a trifocal IOL, which consisted of hydrophilic acrylic material (25%) with hydrophobic surface properties, occurring in a cold region in the winter season.

Case presentation

A young adult with bilateral radiation cataract underwent phacoemulsification using a femtosecond laser and implantation of a trifocal IOL. The trifocal IOL was delivered to the operating theatre 30 min before the surgery. The outside temperature was approximately − 7 °C. The IOL package was warmed using a radiator at approximately 35 °C for 15 min. After the optical region was implanted in the eye, cloudiness was observed, which persisted throughout the operation. Complete clearing of the IOL was apparent after three postoperative hours.

Conclusion

In this case, rapid opacification and clearing of the IOL suggested an acute and transient process. IOLs should be stored and shipped at a constant temperature, and sudden temperature fluctuations should be avoided, especially in the colder seasons.
General practice referral of ‘at risk’ populations to community leisure services: applying the RE-AIM framework to evaluate the impact of a community-based physical activity programme for inactive adults with long-term conditions
Authors: Bird E. L. , Biddle M. S. Y. , Powell J. E.
Published: October 2019

Background

In the UK a high proportion of adults with long-term conditions do not engage in regular physical activity. General practice (GP) referral to community-based physical activity is one strategy that has gained traction in recent years. However, evidence for the real-world effectiveness and translation of such programmes is limited. This study aimed to evaluate the individual and organisational impacts of the ‘CLICK into Activity’ programme - GP referral of inactive adults living with (or at risk of) long-term conditions to community-based physical activity.

Methods

A mixed methods evaluation using the RE-AIM framework was conducted with data obtained from a range of sources: follow-up questionnaires, qualitative interviews, and programme-related documentation, including programme cost data. Triangulation methods were used to analyse data, with findings synthesised across each dimension of the RE-AIM framework.

Results

A total of 602 individuals were referred to CLICK into Activity physical activity sessions. Of those referred, 326 individuals participated in at least one session; the programme therefore reached 30.2% of the 1080 recruitment target. A range of individual-, social-, and environmental-level factors contributed to initial physical activity participation. Positive changes over time in physical activity and other outcomes assessed were observed among participants. Programme adoption at GP surgeries was successful, but the GP referral process was not consistently implemented across sites. Physical activity sessions were successfully implemented, with programme deliverers and group-based delivery identified as having an influential effect on programme outcomes. Changes to physical activity session content were made in response to participant feedback. CLICK into Activity cost £175,000 over 3 years, with an average cost per person attending at least one programme session of £535.

Conclusions

Despite not reaching its recruitment target, CLICK into Activity was successfully adopted. Positive outcomes were associated with participation, although low 6- and 12-month follow-up response rates limit understanding of longer-term programme effects. Contextual and individual factors, which may facilitate successful implementation with the target population, were identified. Findings highlight strategies to be explored in future development and implementation of GP referral to community-based physical activity programmes targeting inactive adults living with (or at risk of) long-term conditions.
What makes health systems resilient against infectious disease outbreaks and natural hazards? Results from a scoping review
Authors: Nuzzo Jennifer B. , Meyer Diane , Snyder Michael , Ravi Sanjana J. , Lapascu Ana , Souleles Jon , Andrada Carolina I. , Bishai David
Published: October 2019

Background

The 2014–2016 Ebola outbreak was a wake-up call regarding the critical importance of resilient health systems. Fragile health systems can become overwhelmed during public health crises, further exacerbating the human, economic, and political toll. Important work has been done to describe the general attributes of a health system resilient to these crises, and the next step will be to identify the specific capacities that health systems need to develop and maintain to achieve resiliency.

Methods

We conducted a scoping review of the literature to identify recurring themes and capacities needed for health system resiliency to infectious disease outbreaks and natural hazards and any existing implementation frameworks that highlight these capacities. We also sought to identify the overlap of the identified themes and capacities with those highlighted in the World Health Organization’s Joint External Evaluation. Sources of evidence included PubMed, Web of Science, OAIster, and the websites of relevant major public health organizations.

Results

We identified 16 themes of health system resilience, including: the need to develop plans for altered standards of care during emergencies, the need to develop plans for post-event recovery, and a commitment to quality improvement. Most of the literature described the general attributes of a resilient health system; no implementation frameworks were identified that could translate these elements into specific capacities that health system actors can employ to improve resilience to outbreaks and natural hazards in a variety of settings.

Conclusions

An implementation-oriented health system resilience framework could help translate the important components of a health system identified in this review into specific capacities that actors in the health system could work to develop to improve resilience to public health crises. However, there remains a need to further refine the concept of resilience so that health systems can simultaneously achieve sustainable transformations in healthcare practice and health service delivery as well as improve their preparedness for emergencies.
Pathological upgrading in prostate cancer treated with surgery in the United Kingdom: trends and risk factors from the British Association of Urological Surgeons Radical Prostatectomy Registry
Authors: Bullock Nicholas , Simpkin Andrew , Fowler Sarah , Varma Murali , Kynaston Howard , Narahari Krishna
Published: October 2019

Background

Accurate grading at the time of diagnosis if fundamental to risk stratification and treatment decision making in patients with prostate cancer. Whilst previous studies have demonstrated significant pathological upgrading and downgrading following radical prostatectomy (RP), these were based on historical cohorts and do not reflect contemporary patient selection and management practices. The aim of this national, multicentre observational study was to characterise contemporary rates and risk factors for pathological upgrading after RP in the United Kingdom (UK).

Methods

All RP entries on the British Association of Urological Surgeons (BAUS) Radical Prostatectomy Registry database of prospectively entered cases undertaken between January 2011 and December 2016 were extracted. Those patients with full preoperative PSA, clinical stage, needle biopsy and subsequent RP pathological grade information were included. Upgrade was defined as any increase in Gleason grade from initial needle biopsy to pathological assessment of the entire surgical specimen. Statistical analysis and multivariate logistic regression were undertaken using R version 3.5 (R Foundation for Statistical Computing, Vienna, Austria).

Results

A total of 17,598 patients met full inclusion criteria. Absolute concordance between initial biopsy and pathological grade was 58.9% (n= 10,364), whilst upgrade and downgrade rates were 25.5% (n= 4489) and 15.6% (n= 2745) respectively. Upgrade rate was highest in those with D’Amico low risk compared with intermediate and high-risk disease (55.7% versus 19.1 and 24.3% respectively,P< 0.001). Although rates varied between year of surgery and geographical regions, these differences were not significant after adjusting for other preoperative diagnostic variables using multivariate logistic regression.

Conclusions

Pathological upgrading after RP in the UK is lower than expected when compared with other large contemporary series, despite operating on a generally higher risk patient cohort. As new diagnostic techniques that may reduce rates of pathological upgrading become more widely utilised, this study provides an important benchmark against which to measure future performance.
Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review
Authors: Gambardella Claudio , Offi Chiara , Clarizia Guglielmo , Romano Roberto Maria , Cozzolino Immacolata , Montella Marco , Di Crescenzo Rosa Maria , Mascolo Massimo , Cangiano Angelo , Di Martino Sergio , Candela Giancarlo , Docimo Giovanni
Published: October 2019

Background

Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described.

Case presentation

We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse.

Conclusion

A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.
The influence of dental experience on a dental implant navigation system
Authors: Sun Ting-Mao , Lee Huey-Er , Lan Ting-Hsun
Published: October 2019

Background

This study evaluated the operating performance of an implant navigation system used by dental students and dentists of prosthodontic background with varying levels of experience. A surgical navigation system and optical tracking system were used, and dentists’ accuracies were evaluated in terms of differences between the positions of actually drilled holes and those of the holes planned using software before surgeries.

Methods

The study participants were 5 dental students or dentists who had studied in the same university and hospital but had different experience levels regarding implants. All participants were trained in operating the AqNavi system in the beginning of the study. Subsequently, using 5 pairs of dental models, each participant drilled 5 implant holes at 6 partially edentulous positions (11, 17, 26, 31, 36, and 47). In total, each participant conducted 30 drilling tests.

Results

In total, 150 tests among 5 dentists at 6 tooth positions (11, 17, 26, 31, 36, and 47) were conducted. Although a comparison of the tests revealed significant differences in the longitudinal error (P < .0001) and angular error (P = .0011), no significant difference was observed in the total error among the dentists.

Conclusions

A relatively long operating time was associated with relatively little implant experience. Through the dental navigation system, dental students can be introduced to dental implant surgery earlier than what was possible in the past. The results demonstrated that the operational accuracy of the dental implant navigation system is not restricted by participants’ implant experience levels. The implant navigation system assists the dentist in the ability to accurately insert the dental implant into the correct position without being affected by his/her own experience of implant surgery.
A comparative study on decision and documentation of refraining from resuscitation in two medical home care units in Sweden
Authors: Sterpu Bogdan , Lindman Pia , Björkhem-Bergman Linda
Published: October 2019

Background

A decision to refrain from cardiopulmonary resuscitation (CPR) in the case of cardiac arrest is recommended in terminally ill patients to avoid unnecessary suffering at time of death. The aim of this study was to describe the frequency of decisions and documentation of “do not attempt cardiopulmonary resuscitation” (DNACPR) in two Medical Home Care Units in Stockholm. Unit A had written guidelines about how to document CPR-decisions in the medical records, including a requirement for a decision to be taken (CPR: yes/no) while Unit B had no such requirement.

Method

The medical records for all patients in palliative phase of their disease at the two Units were reviewed. Data was collected on documentation of decisions about CPR (yes/no), DNACPR-decisions and documentation regarding whether the patient or next-of-kin had been informed about the DNACPR-decision.

Results

In the two Units, 316 and 219 patients in palliative phase were identified. In Unit A 100% of the patients had a CPR-decision (yes/no) compared to 79% in Unit B (p < 0.001). There was no statistically significant difference in DNACPR-decisions between the two Units, 43 and 37%. Documentation about informing the patient regarding the decision was significantly higher in Unit A, 53% compared to 14% at Unit B (p < 0.001). Documentation about informing the next-of-kin was also significantly higher at Unit A; 42% compared to 6% at Unit B (p < 0.001).

Conclusion

Less than 50% of patients in palliative phase had a decision of DNACPR in two Medical Home Care Units in Stockholm. The presence of written guidelines and a requirement for a CPR-decision did not increase the frequency of DNACPR-decisions but was associated with a higher frequency of documentation of decisions and of information given to both the patients and the next-of-kin.
The ‘connectaholic’ behind the curtain: medical student use of computer devices in the clinical setting and the influence of patients
Authors: Clarke Eric , Burns Jane , Bruen Catherine , Crehan Martina , Smyth Erica , Pawlikowska Teresa
Published: October 2019

Background

The use of mobile devices such as tablets and laptops by students to support their learning is now ubiquitous. The clinical setting is an environment, which lends itself to the use of mobile devices as students are exposed to novel clinical scenarios that may require rapid location of information to address knowledge gaps. It is unknown what preferences students have for these devices and how they are used in the clinical environment.

Methods

In this study we explored medical students’ choices and their use of different devices in their first year of clinical attachments. We sought to evaluate learners’ experiences with these devices using a mixed methods approach. All students newly entered into the clinical years were given the option of a MacBook Air or iPad. We surveyed these students using an online survey tool followed by individual semi-structured interviews to explore survey findings in more depth.

Results

Students owned a multitude of devices however their preferences were for the 11 in. MacBook Air Laptop over the iPad mini. Students made constant use of online information to support their clinical learning, however three major themes emerged from the interview data: connection and devices (diverse personal ownership of technology by students and how this is applied to source educational materials), influence and interaction with patients (use of any device in a clinical setting) and influence and interaction with staff. In general students preferred to use their device in the absence of patients however context had a significant influence.

Conclusions

These mobile devices were useful in the clinical setting by allowing access to online educational material. However, the presence of patients, and the behaviour of senior teaching staff significantly influenced their utilisation by students. Understanding the preferences of students for devices and how they use their preferred devices can help inform educational policy and maximise the learning from online educational content.
Working hard to belong: a qualitative study exploring students from black, Asian and minority ethnic backgrounds experiences of pre-registration physiotherapy education
Authors: Hammond John A. , Williams Annabel , Walker Saskia , Norris Meriel
Published: October 2019

Background

Previous research has demonstrated that attainment inequalities exist for students from Black Asian and Minority Ethnic (BAME) groups in pre-registration physiotherapy education. While previous research has explored students from BAME backgrounds experience of university, the context of physiotherapy is unique and is under researched. Therefore the purpose of this study was to explore BAME student experiences during their physiotherapy training.

Methods

Using a phenomenological approach pre-registration BSc and MSc students from BAME backgrounds from two universities who had completed both academic and clinical modules were invited to participate. Focus groups followed a topic guide developed from the literature and were facilitated by physiotherapy educators from outside the host institution. They were digitally recorded, transcribed verbatim and analysed thematically. Analytical triangulation was adopted throughout the research process as a mechanism to enhance rigour.

Results

Seventeen students participated from a range of self-identified BAME backgrounds that were also representative of age, gender and course. Themes derived from the data included: feeling an outsider in reflections of belonging, behaviours by others that marginalise BAME and personal strategies to integrate in physiotherapy despite the lack of power and influence. Collectively these themes demonstrate a range of challenges which students from BAME backgrounds face within both an academic and practice learning environment.

Conclusions

While this may not be surprising based on other disciplines, this study demonstrates that studying physiotherapy as a student from BAME background requires persistence to overcome a series of many implicit challenges. Understanding the experiences of students from BAME backgrounds presents unique opportunities to educate the profession and co-create opportunities for a more diverse profession with practitioners and educators as role models. There is a need for greater training for educators to listen to these students’ voices and their stories, and understand where institutional structures and practices could be modified to enable BAME student inclusion in physiotherapy education and practice.
Quality and barriers of outpatient diabetes care in rural health facilities in Uganda – a mixed methods study
Authors: Birabwa Catherine , Bwambale Mulekya F. , Waiswa Peter , Mayega Roy W.
Published: October 2019

Background

Despite the increasing burden of diabetes in Uganda, little is known about the quality of type 2 diabetes mellitus (T2DM) care especially in rural areas. Poor quality of care is a serious limitation to the control of diabetes and its complications. This study assessed the quality of care and barriers to service delivery in two rural districts in Eastern Uganda.

Methods

This was a mixed methods cross-sectional study, conducted in six facilities. A randomly selected sample of 377 people with diabetes was interviewed using a pre-tested interviewer administered questionnaire. Key informant interviews were also conducted with diabetes care providers. Data was collected on health outcomes, processes of care and foundations for high quality health systems. The study included three health outcomes, six elements of competent care under processes and 16 elements of tools/resources and workforce under foundations. Descriptive statistics were computed to determine performance under each domain, and thematic content analysis was used for qualitative data.

Results

The mean age of participants was 49 years (±11.7 years) with a median duration of diabetes of 4 years (inter-quartile range = 2.7 years). The overall facility readiness score was 73.9%. Inadequacies were found in health worker training in standard diabetes care, availability of medicines, and management systems for services. These were also the key barriers to provision and access to care in addition to lack of affordability. Screening of clients for blood cholesterol and microvascular complications was very low. Regarding outcomes; 56.8% of participants had controlled blood glucose, 49.3% had controlled blood pressure; and 84.0% reported having at least one complication.

Conclusion

The quality of T2DM care provided in these rural facilities is sub-optimal, especially the process of care. The consequences include sub-optimal blood glucose and blood pressure control. Improving availability of essential medicines and basic technologies and competence of health workers can improve the care process leading to better outcomes.
A technical appraisal of guidelines for the management of skin rash in patients on chemotherapy and targeted therapy
Authors: Zhang Fangyuan , Lv Sumei , Feng Yating , Yang Xuan , Qiang Wanmin
Published: October 2019

Background

Skin rash remains one of the most prevalent and troublesome clinical problems experienced by patients on chemotherapy and targeted therapy. To ensure high-quality care, guidelines are seen as the best guidance. Considering the quality of guidelines varies greatly, a systematical appraisal of the methodological quality of guidelines for the management of skin rash in patients on chemotherapeutic drugs and targeted anticancer therapies was undertaken, in order to identify appropriate ones for healthcare professionals.

Methods

A systematic search of databases and Internet was conducted to obtain pertinent guidelines. Two reviewers independently assessed the eligibility of guidelines according to the inclusion criteria. Then the guidelines included were appraised by three researchers with the methodological quality of eligible guideline using Appraisal of Guidelines for Research and Evaluation II (AGREEII).

Results

Totally nineteen guidelines met the inclusion criteria. The quality ranged from good to acceptable in scope and purpose (mean: 78.80%, range: 66.67–94.44%) and clarity of presentation domains (mean: 85.38%, 75.00–91.67%), but not in stakeholder involvement (mean: 50.15%, range: 36.11–75.00%), rigor of development (mean: 23.65%, range: 6.25–70.83%), applicability (mean: 23.96%, range: 4.17–52.08%), and editorial independence domains (mean: 45.18%, range: 0.00–87.50%). Overall, two guidelines were classified as “recommended”.

Conclusions

Only two guidelines were recommended to manage skin rash in patients on chemotherapy and targeted therapies, most guidelines issued were of low to moderate quality. Thus, more attention should be paid to the methodological quality of guideline development in this field.
Barriers and facilitators to development and implementation of a rural primary health care intervention for dementia: a process evaluation
Authors: Morgan Debra , Kosteniuk Julie , O’Connell Megan E. , Kirk Andrew , Stewart Norma J. , Seitz Dallas , Bayly Melanie , Froehlich Chow Amanda , Elliot Valerie , Daku Jean , Hack Tracy , Hoium Faye , Kennett-Russill Deb , Sauter Kristen
Published: October 2019

Background

With rural population aging there are growing numbers of people with dementia in rural and remote settings. The role of primary health care (PHC) is critical in rural locations, yet there is a lack of rural-specific PHC models for dementia, and little is known about factors influencing the development, implementation, and sustainability of rural PHC interventions. Using a community-based participatory research approach, researchers collaborated with a rural PHC team to co-design and implement an evidence-based interdisciplinary rural PHC memory clinic in the Canadian province of Saskatchewan. This paper reports barriers and facilitators to developing, implementing, and sustaining the intervention.

Methods

A qualitative longitudinal process evaluation was conducted over two and half years, from pre- to post-implementation. Data collection and analyses were guided by the Consolidated Framework for Implementation Research (CFIR) which consists of 38 constructs within five domains: innovation characteristics, outer setting, inner setting, individual characteristics, and process. Data were collected via focus groups with the PHC team and stakeholders, smaller team workgroup meetings, and team member interviews. Analysis was conducted using a deductive approach to apply CFIR codes to the data and an inductive analysis to identify barriers and facilitators.

Results

Across all domains, 14 constructs influenced development and implementation. Three domains (innovation characteristics, inner setting, process) were most important. Facilitators were the relative advantage of the intervention, ability to trial on a small scale, tension for change, leadership engagement, availability of resources, education and support from researchers, increased self-efficacy, and engagement of champions. Barriers included the complexity of multiple intervention components, required practice changes, lack of formal incentive programs, time intensiveness of modifying the EMR during iterative development, lack of EMR access by all team members, lack of co-location of team members, workload and busy clinical schedules, inability to justify a designated dementia care manager role, and turnover of PHC team members.

Conclusions

The study identified key factors that supported and hindered the development and implementation of a rural-specific strategy for dementia assessment and management in PHC. Despite challenges related to the rural context, the researcher-academic partnership was successful in developing and implementing the intervention.
The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies
Authors: Fitzgerald Danielle M. , Pollitt Christopher C. , Walsh Donald M. , Sillence Martin N. , de Laat Melody A.
Published: October 2019

Background

The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design.

Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin < 80 μIU/mL) using an OGT prior to the study. The ponies accessed pasture that was fertilised, or unfertilised, for 5 days (4 h/day, with supplemental hay provided at 0.7% bodyweight), with a 10 day period between phases. An OGT was performed after each phase. Glucose, insulin, active glucagon-like peptide-1 (aGLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured in post-prandial blood samples.

Results

The volume of fertilised pasture was five-fold greater than unfertilised pasture, with % non-structural carbohydrates (NSC) similar between all forages. Consuming fertilised pasture increased (P = 0.018) the serum insulin response to an OGT, compared to grazing unfertilised pasture. A limitation of the study was that pasture intake was unable to be quantified. Insulin responses were greater in SD, compared to NSD, ponies (P < 0.001) and remained well above the test cut-off at all times. A subset of ponies, initially screened as NSD, became (more) insulin-dysregulated after pasture access. Further, aGLP-1 was a significant predictor of insulin concentration in this cohort.

Conclusions

Whereas some insulin-dysregulated ponies were comparatively resistant to dietary intervention, others showed markedly different OGT responses following subtle changes in their forage-based diet. This implies that mild/early ID might be unmasked by dietary change, and that dietary management is important in these ponies. However, dietary management alone may not be adequate for all cases of ID.
Evaluation of the efficacy of a trivalent vaccine mixture against a triple challenge with Mycoplasma hyopneumoniae, PCV2, and PRRSV and the efficacy comparison of the respective monovalent vaccines against a single challenge
Authors: Oh Taehwan , Park Kee Hwan , Yang Siyeon , Jeong Jiwoon , Kang Ikjae , Park Changhoon , Chae Chanhee
Published: October 2019

Background

The objective of this study was to assess the efficacy of a trivalent vaccine mixture and compare it to the respective monovalent vaccines against Mycoplasma hyopneumoniae, porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV).

Results

Pigs that were triple challenged with M. hyopneumoniae, PCV2, and PRRSV following vaccination with the trivalent vaccine mixture exhibited a significantly better growth performance when compared to unvaccinated and challenged pigs. A statistical difference was not found when comparing pig populations which were vaccinated with the trivalent vaccine followed by a triple challenge and pigs vaccinated with monovalent M hyopneumoniae vaccine followed by mycoplasmal single challenge in the following areas: M. hyopneumoniae nasal shedding, the number of M. hyopneumoniae-specific interferon-γ secreting cells (IFN-γ-SC), and mycoplasmal lung lesion scores. Pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge resulted in a similar reduction of PCV2 viremia, an increase in the number of PCV2-specific IFN-γ-SC and reduction in interstitial lung lesion scores when compared to pigs vaccinated with a PCV-2 vaccine and challenged with PCV2 only. Lastly, there was a significant difference in the reduction of PRRSV viremia, an increase in PRRSV-specific IFN-γ-SC and a reduction of interstitial lung lesion scores between pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge and pigs vaccinated with a monovalent PRRSV vaccine followed by PRRSV challenge only.

Conclusion

The trivalent vaccine mixture was efficacious against a triple challenge of M. hyopneumoniae, PCV2, and PRRSV. The trivalent vaccine mixture, however, did not result in equal protection when compared against each respective monovalent vaccine, with the largest vaccine occurring within PRRSV.
Ultrasonographic assessment of normal jugular veins in Standardbred horses
Authors: Pasolini Maria Pia , Spinella Giuseppe , Del Prete Chiara , Valentini Simona , Coluccia Pierpaolo , Auletta Luigi , Greco Michele , Meomartino Leonardo
Published: October 2019

Background

Ultrasonography (US) is the recommended imaging technique to evaluate jugular veins. This prospective randomized clinical study was designed to collect a series of B-mode US measurements of manually distended jugular veins in healthy Italian Standardbreds and to find possible correlations between ultrasound measurements and animal morphometric characteristics. Forty-two horses, eight males and 34 females (range 3–22 years; bodyweight 494.4 ± 41.7 kg), were included in the study. The diameters and wall thicknesses of both jugular veins were measured at three different sites of the neck. The differences in ultrasound measurements based on scans, age, gender, side, and site of the neck were evaluated by ANOVA or by the Kruskal-Wallis test. The effects of the morphometric measures on each ultrasound parameter were evaluated by MANOVA (P < 0.05).

Results

The ultrasound measurements did not differ significantly between the three different sites or between genders; hence, they were pooled together in the results. On the transverse scan, the mean dorsoventral and lateromedial diameters were 1.58 ± 0.23 and 2.20 ± 0.25 cm, respectively; the mean superficial and deep wall thicknesses (SWT and DWT) were 0.07 ± 0.01 and 0.08 ± 0.01 cm, respectively. On the longitudinal scan, the mean dorsoventral diameter was 1.59 ± 0.26 cm, and the SWT and DWT were both 0.08 ± 0.01 cm. Neck length, from the caudal edge of the mandible to the thoracic inlet, was related to the dorsoventral diameter in both longitudinal and transverse scan and to the SWT and DWT in transverse scan, whereas height at the withers (measured with tape) and estimated weight were related to the wall thickness. Dividing the subjects into groups by age in years (“young” 3–7, “mature” 8–14, “old” > 14), differences were found for the lateromedial diameter in the transverse scan and the SWT on the longitudinal scan. The main limitation of this study was that only one operator performed the measurements.

Conclusion

The US measurements of the jugular veins and their relationship with morphometric measures reported in this manuscript might be considered as guidelines both for early diagnosis and monitoring jugular vein abnormalities in healthy Italian Standardbred horses.
Tissue-specific responses of antioxidant pathways to poor hygiene conditions in growing pigs divergently selected for feed efficiency
Authors: Sierżant K. , Perruchot M-H. , Merlot E. , Le Floc’h N. , Gondret F.
Published: October 2019

Background

Poor hygiene of housing induces a systemic inflammatory response. Because inflammation and oxidative stress are processes that can sustain each other, the ways pigs are able to activate their antioxidant defenses are critical for production performance and health during periods when the immune system is solicited. Selection for production performance can also influence reactive oxygen species (ROS) production and expression levels of genes involved in cellular response to oxidative stress in different tissues. To establish the extent by which poor hygiene and selection for feed efficiency affected redox status, pigs divergently selected for residual feed intake (RFI) were housed in poor or good hygiene during 6 weeks. At the end, blood was collected in all pigs, and half of them were killed for tissue sampling. The remaining pigs were reared in good hygiene conditions during a recovery period of 7–8 weeks.

Results

At week 6, poor hygiene was associated with a lower total antioxidant capacity assessed by plasma ferric reducing ability in all pigs, and with greater plasma levels of hydrogen peroxides in the high RFI pigs (less efficient). Adipose tissue of high RFI pigs exhibited higher activities of catalase and glutathione reductase, and greater thiobarbituric acid reactive substances (TBARS) concentrations when compared with the low RFI pigs (more efficient). Poor hygiene conditions activated the antioxidant enzymes activities (glutathione reductase, superoxide dismutase and catalase) in adipose tissue of both lines, but led to higher ROS production by mature adipocytes isolated from the high RFI pigs only. In liver and muscle, there were only minor changes in antioxidant molecules due to genetics and hygiene conditions. After the resilience period, adipose tissue of pigs previously challenged by poor hygiene maintained higher antioxidant enzyme activities, and for the high RFI line, displayed higher TBARS concentrations.

Conclusions

Pigs selected for improved feed efficiency showed a lower susceptibility to oxidative stress induced by poor hygiene conditions. This could led to a lower inflammatory response and less impaired growth when these pigs are facing sanitary challenges during the production period.
Widespread co-endemicity of Trypanosoma species infecting cattle in the Sudano-Sahelian and Guinea Savannah zones of Cameroon
Authors: Paguem Archile , Abanda Babette , Ndjonka Dieudonné , Weber Judith Sophie , Ngomtcho Sen Claudine Henriette , Manchang Kingsley Tanyi , Adoulmoumini Mamoudou , Eisenbarth Albert , Renz Alfons , Kelm Sørge , Achukwi Mbunkah Daniel
Published: October 2019

Background

African animal trypanosomosis remains the major constraint of livestock production and livelihood of pastoral communities in Cameroon. Despite several decades of vector and parasite control efforts, it has not been eradicated. Alternative and sustainable control strategies require a sound knowledge of the local species, strains and vectors. In the Sudano-Sahelian and Guinea Savannah of Cameroon the prevalence and genetic diversity of trypanosomes infecting cattle was investigated by microscopy of cattle blood buffy coat and molecular methods using generic primers targeting parts of the internal transcribed spacer 1 (ITS-1) and encoded glycosomal glyceraldehyde 3-phosphate dehydrogenase-gene (gGAPDH).

Results

A total of 1176 randomly chosen cattle from five divisions in the Sudano-Sahelian and Guinea Savannah of Cameroon were examined. The overall prevalence of trypanosomes by microscopy was 5.9% (56/953) in contrast to 53.2% (626/1176) when molecular tools were used. This indicated a limited sensitivity of microscopy in subclinical infections with frequently low parasitemia. Three trypanosome species were identified by light microscopy: T. vivax (2.3%), T. brucei (3.7%) and T. congolense (3.0%), whereas five were identified by PCR, namely T. grayi/T. theileri (30.8%), T. vivax (17.7%), T. brucei (14.5%) and T. congolense (5.1%). Unexpected cases of T. grayi (n = 4) and T. theileri (n = 26) were confirmed by sequencing. Phylogenetic analysis of the gGAPDH revealed the presence of T. vivax, clade A and T. vivax clade C, which were co-endemic in the Faro et Deo division.

T. grayi/T. theileri were the predominant species infecting cattle in tsetse free areas. In contrast, T. vivax, T. brucei and T. congolense were more abundant in areas where the Glossina-vectors were present.

Conclusions

The abundance of pathogenic trypanosomes in tsetse infested areas is alarming and even more, the occurrence of T. vivax, T. brucei, T. congolense, T. theileri and T. grayi in tsetse-free areas implies that tsetse control alone is not sufficient to control trypanosomosis in livestock. To implement control measures that reduce the risk of spread in tsetse free areas, close monitoring using molecular tools and a thorough search for alternative vectors of trypanosomes is recommended.
The caudate nucleus undergoes dramatic and unique transcriptional changes in human prodromal Huntington’s disease brain
Authors: Agus Filisia , Crespo Diego , Myers Richard H. , Labadorf Adam
Published: October 2019

Background

The mechanisms underlying neurodegeneration in the striatum of Huntingon’s Disease (HD) brain are currently unknown. While the striatum is massively degenerated in symptomatic individuals, which makes cellular characterization difficult, it is largely intact in asymptomatic HD gene positive (HD+) individuals. Unfortunately, as striatal tissue samples from HD+ individuals are exceedingly rare, recent focus has been on the Brodmann Area 9 (BA9), a relatively unaffected region, as a surrogate tissue. In this study, we analyze gene expression in caudate nucleus (CAU) from two HD+ individuals and compare the results with healthy and symptomatic HD brains.

Methods

High-throughput mRNA sequencing (mRNA-Seq) datasets were generated from post-mortem CAU of 2 asymptomatic HD+ individuals and compared with 26 HD and 56 neurologically normal controls. Datasets were analyzed using a custom bioinformatic analysis pipeline to identify and interpret differentially expressed (DE) genes. Results were compared to publicly available brain mRNA-Seq datasets from the Genotype-Tissue Expression (GTEx) project. The analysis employed current state of the art bioinformatics tools and tailored statistical and machine learning methods.

Results

The transcriptional profiles in HD+ CAU and HD BA9 samples are highly similar. Differentially expressed (DE) genes related to the heat shock response, particularly HSPA6 and HSPA1A, are common between regions. The most perturbed pathways show extensive agreement when comparing disease with control. A random forest classifier predicts that the two HD+ CAU samples strongly resemble HD BA9 and not control BA9. Nonetheless, when genes were prioritized by their specificity to HD+ CAU, pathways spanning many biological processes emerge. Comparison of HD+ BA9 with HD BA9 identified NPAS4 and REST1/2 as potential early responders to disease and reflect the active disease process.

Conclusions

The caudate nucleus in HD brain is dramatically affected prior to symptom onset. Gene expression patterns observed in the HD BA9 are also present in the CAU, suggesting a common response to disease. Substantial caudate-specific differences implicate many different biological pathways including metabolism, protein folding, inflammation, and neurogenic processes. While these results are at best trends due to small sample sizes, these results nonetheless provide the most detailed insight to date into the primary HD disease process.
Co-mutations of TP53 and KRAS serve as potential biomarkers for immune checkpoint blockade in squamous-cell non-small cell lung cancer: a case report
Authors: Fang Cheng , Zhang Chu , Zhao Wei-Qing , Hu Wen-Wei , Wu Jun , Ji Mei
Published: October 2019

Background

Unprecedented durable responses are identified in clinical studies to target the signaling of programmed cell death protein-1 (PD-1) as well as its ligand (PD-L1) in patients with squamous-cell non-small cell lung cancer (NSCLC). However, factors predicting the patient subtypes that are responsive to PD-1/PD-L1inhibitors have not been fully understood yet. Biomarkers, like PD-L1 expression, tumor mutational burden(TMB), DNA mismatch repair deficiency (dMMR), and tumor-infiltrating lymphocytes (TILs), have been utilized to select patients responsive to PD-1/PD-L1inhibitors in the clinic, but each of them has limited use. Lung adenocarcinoma patients with a mutation of TP53 or KRAS, particularly those with co-mutations of TP53 and KRAS, can benefit from anti–PD-1 treatment.

Case presentation

In this study, the co-mutations of TP53 and KRAS in a 64-year-old non-smoking man with squamous-cell NSCLC patient was described using the next-generation sequencing (NGS) technology. The patient was treated with the pembrolizumab combined with gemcitabine as the salvage therapy, and a marked partial response could be attained, which had persisted for over 7 months.

Conclusion

In addition to testing common driving genes, like EGFR, ALK, ROS1 and BRAF, both TP53, and KRAS should also be considered in advanced or metastatic squamous-cell NSCLC.TP53 and KRAS co-mutations in squamous-cell NSCLC can be a potential factor to assess possible response to PD-1 blockade immunotherapy, but further studies with more cases are needed to confirm the prediction power.
Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy
Authors:   CINRG Investigators, Kelley Eli F. , Cross Troy J. , Snyder Eric M. , McDonald Craig M. , Hoffman Eric P. , Bello Luca
Published: October 2019

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3–25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.
Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes
Authors: Coleman Ruth L. , Scott Charles A. B. , Lang Zhihui , Bethel M. Angelyn , Tuomilehto Jaakko , Holman Rury R.
Published: October 2019

Background

Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes.

Methods

We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes.

Results

Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67–0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89–1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively.

Conclusions

Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.