bluuebunny/crossref_metadata_2025 huggingface dataset:
A consensus-based process identifying physical therapy and exercise treatments for patients with degenerative meniscal tears and knee OA: the TeMPO physical therapy interventions and home exercise program
Authors: Safran-Norton Clare E. , Sullivan James K. , Irrgang James J. , Kerman Hannah M. , Bennell Kim L. , Calabrese Gary , Dechaves Leigh , Deluca Brian , Gil Alexandra B. , Kale Madhuri , Luc-Harkey Brittney , Selzer Faith , Sople Derek , Tonsoline Peter , Losina Elena , Katz Jeffrey N.
Published: November 2019

Background

Knee osteoarthritis (OA) is prevalent and often associated with meniscal tear. Physical therapy (PT) and exercise regimens are often used to treat OA or meniscal tear, but, to date, few programs have been designed specifically for conservative treatment of meniscal tear with concomitant knee OA. Clinical care and research would be enhanced by a standardized, evidence–based, conservative treatment program and the ability to study the effects of the contextual factors associated with interventions for patients with painful, degenerative meniscal tears in the setting of OA. This paper describes the process of developing both a PT intervention and a home exercise program for a randomized controlled clinical trial that will compare the effectiveness of these interventions for patients with knee pain, meniscal tear and concomitant OA.

Methods

This paper describes the process utilized by an interdisciplinary team of physical therapists, physicians, and researchers to develop and refine a standardized in-clinic PT intervention, and a standardized home exercise program to be carried out without PT supervision. The process was guided in part by Medical Research Council guidance on intervention development.

Results

The investigators achieved agreement on an in-clinic PT intervention that included manual therapy, stretching, strengthening, and neuromuscular functional training addressing major impairments in range of motion, musculotendinous length, muscle strength and neuromotor control in the major muscle groups associated with improving knee function. The investigators additionally achieved agreement on a progressive, protocol-based home exercise program (HEP) that addressed the same major muscle groups. The HEP was designed to allow patients to perform and progress the exercises without PT supervision, utilizing minimal equipment and a variety of methods for instruction.

Discussion

This multi-faceted in-clinic PT program and standardized HEP provide templates for in-clinic and home-based care for patients with symptomatic degenerative meniscal tear and concomitant OA. These interventions will be tested as part of the Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial.

Trial registration

The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 on February 14, 2017. TeMPO was also approved by the Institutional Review Board at Partners HealthCare/Brigham and Women’s Hospital.
Surface-projection-based transperineal cognitive fusion targeted biopsy of the prostate: an original technique with a good cancer detection rate
Authors: Wang Lei , Wang Xiaofei , Zhao Wenfeng , Zhao Zichen , Li Zhihu , Fei Shengmin , Zhu He , Ji Xiang , Yang Bing , Li Ningchen , Na Yanqun
Published: November 2019

Background

To report a new standardized cognitive fusion technique on transperineal targeted biopsy (TB) of prostate, and to evaluate its efficacy for cancer detection combined with systematic biopsy (SB) .

Methods

We present a retrospective review of consecutive patients undergoing multiparametric magnetic resonance (mpMRI) imaging of the prostate with subsequent transperineal prostate biopsy from January 2016 to December 2018. A free-hand 12-core SB was performed for each patient. PI-RADS 3–5 lesions were further targeted for biopsy with our TB technique. Firstly, a central point of suspicious lesion (B′) was registered cognitively on a transverse section of transrectal ultrasound (TRUS). Then, biopsy gun punctured vertically through a fixed pioneer site (A) on skin of perineum, and deep into the TRUS section to get A’. Next, targeted site (B), the surface-projection of B′, would be determined on skin of perineum by A and distance from B′ to A’. Finally, puncture through B to reach B′. Pathological findings of SB and TB were analyzed.

Results

A total of 126 patients underwent transperineal prostate biopsy (47 SB only, 79 SB + TB). The age of the patients was 68.7 ± 9.2 years. The median preoperative PSA value was 11.8 ng/mL. Preoperative prostate volume was 60.5 ± 50.0 mL. The numbers of patients with PI-RADS scores of 1 through 5 were 4, 43, 27, 21 and 31, respectively. The overall detection rate of cancer was 61/126 (48.4%), and it was significantly higher in the combination cohort (56/79, 70.9%) compared with the SB only cohort (5/47, 10.6%, p<0.001). When focused on the combination cohort, TB detected a similar overall rate of PCa (53/79, 67.1% vs 52/79, 65.8%; p = 0.87) compared with SB. The clinically significant PCa (csPC) detection rate was 52/79 (65.8%), while for TB and SB the csPC/PC rate was 51/53 (96.2%) and 48/52 (92.3%), respectively(p = 0.44). TB demonstrated a better sampling performance (positive rate for each core) compared with SB (51.0% vs 31.3%, p < 0.001).

Conclusions

Surface-projection-based transperineal cognitive fusion targeted biopsy of the prostate has a good efficacy in detecting PCa.
Bilateral adrenal hemorrhage after hip arthroplasty: an initially misdiagnosed case
Authors: Wang Lei , Wang Xiao-fei , Qin Ying-chao , Chen Jia , Shang Cun-hai , Sun Guo-feng , Li Ning-chen
Published: November 2019

Background

Bilateral adrenal hemorrhage (BAH) is a rare but potentially catastrophic condition. Its clinical manifestation is often non-specific and sometimes difficult to be diagnosed in time.

Case summary

A 57-year-old woman, who presented with severe fatigue, nausea and vomiting after left hip arthroplasty due to her femoral neck fracture in a local hospital, was transferred to our medical center. Laboratory results revealed significant hyponatremia, low serum cortisol and elevated serum ACTH. Computed tomography (CT) showed a bilateral adrenal mass, measured 3.6 × 2.7 cm on the left and 3.4 × 2.3 cm on the right. Further magnetic resonance imaging (MRI) confirmed the diagnosis of BAH. The patient was prescribed with oral prednisolone acetate, 5 mg, tid, and her condition improved gradually. Nine months after, the patient was in good condition with 5 mg prednisolone acetate per day. CT revealed a clearly shrunken adrenal mass compared with 9 months ago.

Conclusions

This case illustrates the difficulty in making the diagnosis of BAH with atypical presentation. Such cases necessitate greater alertness on the part of the clinician and require rapid diagnosis and prompt glucocorticoid replacement for better clinical outcomes.
Disruption of a putative mitochondrial oxaloacetate shuttle protein in Aspergillus carbonarius results in secretion of malic acid at the expense of citric acid production
Authors: Yang Lei , Linde Tore , Hossain Abeer H. , Lübeck Mette , Punt Peter J. , Lübeck Peter S.
Published: November 2019

Background

In filamentous fungi, transport of organic acids across the mitochondrial membrane is facilitated by active transport via shuttle proteins. These transporters may transfer different organic acids across the membrane while taking others the opposite direction. InAspergillus niger, accumulation of malate in the cytosol can trigger production of citric acid via the exchange of malate and citrate across the mitochondrial membrane. Several mitochondrial organic acid transporters were recently studied inA. nigershowing their effects on organic acid production.

Results

In this work, we studied another citric acid producing fungus,Aspergillus carbonarius, and identified by genome-mining a putative mitochondrial transporter MtpA, which was not previously studied, that might be involved in production of citric acid. This gene namedmtpAencoding a putative oxaloacetate transport protein was expressed constitutively inA. carbonariusbased on transcription analysis. To study its role in organic acid production, we disrupted the gene and analyzed its effects on production of citric acid and other organic acids, such as malic acid. In total, 6 transformants with genemtpAdisrupted were obtained and they showed secretion of malic acid at the expense of citric acid production.

Conclusion

A putative oxaloacetate transporter gene which is potentially involved in organic acid production byA. carbonariuswas identified and further investigated on its effects on production of citric acid and malic acid. ThemtpAknockout strains obtained produced less citric acid and more malic acid than the wild type, in agreement with our original hypothesis. More extensive studies should be conducted in order to further reveal the mechanism of organic acid transport as mediated by the MtpA transporter.
Identification of a potentially avoidable cardiopulmonary resuscitation in hematology and oncology wards
Authors: Choi Yeonjoo , Kim Jin Won , Suh Koung Jin , Lim Yoo-Joo , Lee Ji Yun , Kang Beo-Deul , Kim Ji-Won , Kim Se-Hyun , Lee Jeong-Ok , Kim Yu Jung , Lee Keun-Wook , Kim Jee Hyun , Bang Soo-Mee , Lee Jong Seok
Published: November 2019

Background

In-hospital cardiopulmonary resuscitation (CPR) is one of undesirable situations. We tried to identify and characterize a potentially avoidable CPR in cancer patients who were hospitalized in hematology and oncology wards.

Methods

A potentially avoidable CPR was determined based on chemotherapy setting, disease status and clinical situation at the time when a cardiopulmonary arrest occurred, by using a consensus-driven medical records review of two physicians.

Results

One hundred thirty-seven patients among 12,437 patients hospitalized at hematology and oncology wards between March 2003 and June 2015 (1.1%) underwent a CPR. Eighty-eight patients (64.2%) were men. The majority of patients with a CPR had lung cancer (41, 29.9%), hematologic malignancy (24, 17.5%), stomach cancer (23, 16.8%) or lymphoma (20, 14.6%). A potentially avoidable CPR was identified in 51 patients (37.2%). In a multivariate analysis, advanced diseases and certain tumor types (e.g., lung cancer, lymphoma) were significant risk factors for a potentially avoidable CPR. Of patients who received a potentially avoidable CPR, 29 patients (56.9%) did not have a do-not-resuscitate documentation. A first return of spontaneous circulation rate (ROSC) and in-hospital survival rate (IHSR) were much lower in patients with a potentially avoidable CPR than those with a CPR that was not avoidable (ROSC: 39.2% vs 53.5%, P = 0.106; IHSR: 2.0% vs 12.8%, P = 0.032, respectively).

Conclusions

A potentially avoidable CPR was common at hematology and oncology wards. A potentially avoidable CPR frequently occurred in advanced diseases and certain tumor types. Furthermore, cancer patients who received a potentially avoidable CPR showed the worse prognosis.
The potential of antioxidant-rich Maoberry (Antidesma bunius) extract on fat metabolism in liver tissues of rats fed a high-fat diet
Authors: Ngamlerst Chattraya , Udomkasemsab Arunwan , Kongkachuichai Ratchanee , Kwanbunjan Karunee , Chupeerach Chaowanee , Prangthip Pattaneeya
Published: November 2019

Backgound

Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD.

Methods

We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet–induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated.

Results

Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P < 0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups.

Conclusions

The improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.
Anti-inflammatory effect of Vaccinium oldhamii stems through inhibition of NF-κB and MAPK/ATF2 signaling activation in LPS-stimulated RAW264.7 cells
Authors: Kim Ha Na , Baek Jueng Kyu , Park Su Bin , Kim Jeong Dong , Son Ho-Jun , Park Gwang Hun , Eo Hyun Ji , Park Jae Ho , Jung Hyuk-Sang , Jeong Jin Boo
Published: November 2019

Background

Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells.

Methods

Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot.

Results

Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation.

Conclusions

These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.
Knowledge on leprosy and its management among primary healthcare providers in two districts of Bangladesh
Authors: Kabir Humayun , Hossain Shahed
Published: November 2019

Background

In 2013, Lepra Bangladesh (a non-government organization) and the National Leprosy Programme of the Directorate General of Health Services under the Ministry of Health and Family Welfare, Bangladesh implemented a 3 years project entitled “2015 and Beyond: Poverty Reduction through Strengthened Health Systems”. The aims of this Health System Strengthening (HSS) project were to improve quality of leprosy services through service delivery, capacity development, curriculum development, improved collaboration, coordination, operational research and knowledge sharing to identify and treat leprosy in order to contribute to strengthen existing health systems. We evaluated the changes in knowledge of primary and community level healthcare providers about cardinal signs, course of leprosy treatment, and drug use for paucibacillary (PB) and multibacillary (MB) leprosy cases.

Methods

We conducted two surveys using purposive sampling technique in two pilot districts: Bogra and Moulvibazar. The first survey was conducted before implementing the HSS project from March to June 2014 among 98 providers. The end-line survey was conducted in November 2015 and included 49 providers. The interview was conducted using the same pre-tested structured questionnaire. Descriptive statistics followed by further analysis was done including proportions, 90% confidence intervals, and p values were calculated for the selected variables.

Results

The primary and community level healthcare providers demonstrated significant increases in knowledge on one cardinal sign (definite loss of sensation in a pale -hypopigmented- or reddish skin patch), doses and courses for the adult PB and MB cases and duration of Multi-Drug Therapy (MDT) course at the end line compared to the beginning of the project. All the providers except TB and Leprosy Control Assistants demonstrated statistically significant decreases in knowledge at the end-line compared to the baseline about supportive counseling.

Conclusions

HSS activities including training and capacity building of the providers recorded significant increase of knowledge on types of leprosy, one cardinal sign, courses of MDT and drug use for the adult PB and MB cases and use MDT for leprosy treatment among the service providers at the end-line. Any health systems strengthening project should incorporate a capacity building approach within the programme all through.
The structure of the quality of clinical practice guidelines with the items and overall assessment in AGREE II: a regression analysis
Authors: Hatakeyama Yosuke , Seto Kanako , Amin Rebeka , Kitazawa Takefumi , Fujita Shigeru , Matsumoto Kunichika , Hasegawa Tomonori
Published: November 2019

Background

The Appraisal of Guidelines for Research & Evaluation (AGREE) II has been widely used to evaluate the quality of clinical practice guidelines (CPGs). While the relationship between the overall assessment of CPGs and scores of six domains were reported in previous studies, the relationship between items constituting these domains and the overall assessment has not been analyzed. This study aims to investigate the relationship between the score of each item and the overall assessment and identify items that could influence the overall assessment.

Methods

All Japanese CPGs developed using the evidence-based medicine method and published from 2011 to 2015 were used. They were independently evaluated by three appraisers using AGREE II. The evaluation results were analyzed using regression analysis to evaluate the influence of 6 domains and 23 items on the overall assessment.

Results

A total of 206 CPGs were obtained. All domains and all items except one were significantly correlated to the overall assessment. Regression analysis revealed that Domain 3 (Rigour of Development), Domain 4 (Clarity of Presentation), Domain 5 (Applicability), and Domain 6 (Editorial Independence) had influence on the overall assessment. Additionally, four items of AGREE II, clear selection of evidence (Item 8), specific/unambiguous recommendations (Item 15), advice/tools for implementing recommendations (Item 19), and conflicts of interest (Item 22), significantly influenced the overall assessment and explained 72.1% of the variance.

Conclusions

These four items may highlight the areas for improvement in developing CPGs.
Scoping review of acute stroke care management and rehabilitation in low and middle-income countries
Authors: Chimatiro George Lameck , Rhoda Anthea J.
Published: November 2019

Background

Stroke is a major public health concern, affecting millions of people worldwide. Care of the condition however, remain inconsistent in developing countries. The purpose of this scoping review was to document evidence of stroke care and service delivery in low and middle-income countries to better inform development of a context-fit stroke model of care.

Methods

An interpretative scoping literature review based on Arksey and O’Malley’s five-stage-process was executed. The following databases searched for literature published between 2010 and 2017; Cochrane Library, Credo Reference, Health Source: Nursing/Academic Edition, Science Direct, BioMed Central, Cumulative Index to Nursing and Allied Health Literature (CINNAHL), Academic Search Complete, and Google Scholar. Single combined search terms included acute stroke, stroke care, stroke rehabilitation, developing countries, low and middle-income countries.

Results

A total of 177 references were identified. Twenty of them, published between 2010 and 2017, were included in the review. Applying the Donebedian Model of quality of care, seven dimensions of stroke-care structure, six dimensions of stroke care processes, and six dimensions of stroke care outcomes were identified. Structure of stroke care included availability of a stroke unit, an accident and emergency department, a multidisciplinary team, stroke specialists, neuroimaging, medication, and health care policies. Stroke care processes that emerged were assessment and diagnosis, referrals, intravenous thrombolysis, rehabilitation, and primary and secondary prevention strategies. Stroke-care outcomes included quality of stroke-care practice, functional independence level, length of stay, mortality, living at home, and institutionalization.

Conclusions

There is lack of uniformity in the way stroke care is advanced in low and middle-income countries. This is reflected in the unsatisfactory stroke care structure, processes, and outcomes. There is a need for stroke care settings to adopt quality improvement strategies. Health ministry and governments need to decisively face stroke burden by setting policies that advance improved care of patients with stroke. Stroke Units and Recombinant Tissue Plasminogen Activator (rtPA) administration could be considered as both a structural and process necessity towards improvement of outcomes of patients with stroke in the LMICs.
Exploring the role of external experts in supporting staff to implement psychosocial interventions in care home settings: results from the process evaluation of a randomized controlled trial
Authors: Surr Claire A. , Shoesmith Emily , Griffiths Alys W. , Kelley Rachael , McDermid Joanne , Fossey Jane
Published: November 2019

Background

Psychosocial interventions offer opportunities to improve care for people with dementia in care homes. However, implementation is often led by staff who are not well prepared for the role. Some interventions use external experts to support staff. However little is known about external expert, care home staff and manager perceptions of such support. This paper addresses this gap.

Methods

Multi-methods study within a process evaluation of a cluster randomised controlled trial of Dementia Care Mapping™ (DCM). Interviews were conducted with six external experts who also completed questionnaires, 17 care home managers and 25 care home staff responsible for DCM implementation. Data were analysed using descriptive statistics and template analysis.

Results

Three themes were identified: the need for expert support, practicalities of support and broader impacts of providing support. Expert support was vital for successful DCM implementation, although the five-days provided was felt to be insufficient. Some homes felt the support was inflexible and did not consider their individual needs. Practical challenges of experts being located at a geographical distance from the care homes, limited when and how support was available. Experts gained knowledge they were able to then apply in delivering DCM training. Experts were not able to accurately predict which homes would be able to implement DCM independently in future cycles.

Conclusions

An external expert may form a key component of successful implementation of psychosocial interventions in care home settings. Future research should explore optimal use of the expert role.
Melatonin decreases in vitro viability and migration of spheres derived from CF41.Mg canine mammary carcinoma cells
Authors: Serrano Consuelo , Guzmán Sofía , Arias Jose Ignacio , Torres Cristian Gabriel
Published: November 2019

Background

Mammary cancer is a common disease affecting female dogs, where approximately 50% of the cases are malignant. There is a subpopulation of cancer cells with stem cell-like features within the tumour microenvironment, which can form in vitro spheres, cell structures that grow in anchor-free conditions. This cell population shows resistance to conventional antitumor treatments explaining in part the recurrence of some type of cancers. It has been previously reported that spheres derived from CF41.Mg canine mammary carcinoma cells exhibit several stemness features. Melatonin has shown antitumor effects on cancer mammary cells; nevertheless, its effects have been poorly evaluated on canine mammary cancer stem-like cells. In this regard, it has described that melatonin decreases the expression of OCT-4 in CMT-U2229 mammary cancer cells, a transcription factor that participates in the modulation of self-renewal and drug resistance in cancer stem-like cells. The aim of this study was to compare the effects of melatonin on viability and migration of canine mammary carcinoma CF41.Mg-spheres, and CF41.Mg-parental cells. CF41.Mg cells were grown in DMEM high-glucose medium containing 10% bovine foetal serum. CF41.Mg-spheres were cultured in ultra-low attachment plates with serum-free DMEM/F12 containing several growth factors. Cell viability (MTS reduction) and migration (transwell) assays were conducted in presence of melatonin (0.01, 0.1 or 1 mM).

Results

Melatonin decreased cell viability at 1 mM (P < 0.05), with a significant reduction in spheres compared to parental cells at 24 and 48 h (P < 0.05). Cell migration was inhibited in response to non-cytotoxic concentration of melatonin (0.1 mM) (P < 0.05) in spheres and monolayer of cells, no significant differences were detected between both cell subtypes.

Conclusions

These results indicate that melatonin reduces viability and migration of CF41.Mg cells, where spheres exhibit greater sensitivity to the hormone. Thus, melatonin represents a valuable potential agent against mammary cancer cells, especially cancer stem-like cells.
Collie Eye Anomaly in Australian Kelpie dogs in Poland
Authors: Kucharczyk Natalia , Cislo-Pakuluk Anna , Bedford Peter
Published: November 2019

Background

To report the occurrence of choroidal hypoplasia in the Australian Kelpie breed in Poland, the affected dogs testing positive for the Collie Eye Anomaly NHEJ1 gene mutation.

Case presentations

Choroidal hypoplasia (CH) was initially diagnosed in a young female Australian Kelpie presented for routine ophthalmological examination prior to breeding. Indirect ophthalmoscopy revealed tigroid fundi bilaterally with areas of abnormally arranged choroidal vasculature temporal to the optic disc. These lesions had the appearance of the choroidal hypoplasia diagnostic for Collie Eye Anomaly, a genetically determined disease seen most commonly in Collie types.

The DNA based test for the NHEJ1 gene mutation that is confirmatory for Collie Eye Anomaly proved the dog to be homozygous for this mutation. Twenty one other related dogs were subsequently examined genetically, the dam proving to be affected and eight others were shown to be carriers.

Conclusions

This report demonstrates that Collie Eye Anomaly is present in a Polish bred Australian Kelpie line and as such breeders in this country and those importing dogs or semen internationally should be aware of other possible cases.
Potential risks and solutions for sharing genome summary data from African populations
Authors: Tiffin Nicki
Published: November 2019

Genome data from African population can substantially assist the global effort to identify aetiological genetic variants, but open access to aggregated genomic data from these populations poses some significant risks of community- and population- level harms. A recent amendment to National Institutes of Health policy, following various engagements with predominantly North American scientists, requires that genomic summary results must be made available openly on the internet without access oversight or controls.

The policy does recognise that some sensitive, identifiable population groups might be harmed by such exposure of their data, and allows for exemption in these cases. African populations have a very wide and complex genomic landscape, and because of this diversity, individual African populations may be uniquely re-identified by their genomic profiles and genome summary data. Given this identifiability, combined with additional vulnerabilities such as poor access to health care, socioeconomic challenges and the risk of ethnic discrimination, it would be prudent for the National Institutes of Health to recognise the potential of their current policy for community harms to Africans; and to exempt all African populations as sensitive or vulnerable populations with regard to the unregulated exposure of their genome summary data online.

Three risk-mitigating mechanisms for sharing genome summary results from African populations to inform global genomic health research are proposed here; namely use of the Beacon Protocol developed by the Global Alliance for Genomics and Health, user access control through the planned African Genome Variation Database, and regional aggregation of population data to protect individual African populations from re-identification and associated harms.
Single-inhaler triple therapy in patients with chronic obstructive pulmonary disease: a systematic review
Authors: Langham Sue , Lewis Jen , Pooley Nick , Embleton Nina , Langham Julia , Han MeiLan K. , Chalmers James D.
Published: November 2019

Background

Guidelines recommend that treatment with a long-acting β2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base.

Methods

We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations.

Results

We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15–52% compared with LAMA/LABA, 15–35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25–50 (preventing one patient from having an event) and the event-based number needed to treat of around 3–11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons.

Conclusion

The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials.

Trial registration

PROSPERO #CRD42018102125.
How can the integrity of occupational and environmental health research be maintained in the presence of conflicting interests?
Authors: Baur Xaver , Soskolne Colin L. , Bero Lisa A.
Published: November 2019

Background

The sciences, and especially the research subspecialties of occupational and environmental health, are being misused. The misuse serves to interfere with the advancement of policies that depend on rational evidence needed for policies to protect public health.

Methods

We selectively surveyed the independent scientific literature. In addition, the efforts of respected international professional organizations of scientists whose focus is on maintaining and improving public health have been considered. This commentary is unique in assembling not only the factual basis for sounding alarms about significant bias in occupational and environmental health research, but also about the manipulative mechanisms used, and, in turn, the methods needed to keep science honest.

Results

Scientific integrity is based on the principle that research is conducted as objectively as possible; it cannot be compromised by special interests whose primary goals are neither to seek truth nor to protect human health. Evidence demonstrates a significant risk of bias in research reports sponsored by financial interests. Practices of corporate malfeasance include the orchestrated contamination of editorial boards of peer-reviewed scientific journals with industry apologists; interference with activities of national regulatory bodies and international review panels engaged in safeguarding occupational and public health; constructing roadblocks by capitalizing on uncertainty to undermine scientific consensus for much-needed government regulation of carcinogenic, endocrine-disrupting and/or immunotoxic agents; promoting “causation” criteria that lack foundation and effectively block workers’ access to legal remedies for harms from occupational exposures resulting in morbidity and premature mortality; and, violating standards of professional conduct by seducing reputable scientists with financial incentives that make them beholden to corporate agendas.

Conclusions

Well-orchestrated assaults on science continue unabated and must now be met head-on. Success could be achieved by promoting and protecting the integrity of research. Furthermore, avoiding influence by conflicted corporate affiliates in occupational and public health regulations is needed. Identifying, managing and, ideally, eliminating corporate influence on science and science policy are needed to protect research integrity. Protecting the public’s health, preventing disease, and promoting well-being must be the unambiguous goals of research in occupational and environmental health.
Global longitudinal strain as an Indicator of cardiac Iron overload in thalassemia patients
Authors: Abtahi Firoozeh , Abdi Alireza , Jamshidi Saideh , Karimi Mehran , Babaei-Beigi Mohammad Ali , Attar Armin
Published: November 2019

Background and objective

Cardiac involvement due to iron overload is the most common cause of morbidity and mortality in patients with thalassemia, and many patients remain asymptomatic until the late stages. Therefore, early detection of heart problems in such patients at subclinical stages can improve the prognosis of these patients. We investigated the role of speckled tracking (SI) and tissue Doppler echocardiography (TDI) in early detection of iron overload in these patients.

Methods

52 thalassemic patients who were receiving regular blood transfusion with normal global LV function were examined by two- and three-dimensional echocardiography. Cardiac MRI was done and T2* images were considered as the non-invasive gold standard for evaluating cardiac iron deposition. Serum ferritin level was assessed and the relationships between serum ferritin levels and echo finding with cardiac MRI T2* was investigated.

Results

No significant relationship was seen between serum ferritin levels and cardiac MRI T2*. Among the echocardiographic findings, septal systolic myocardial velocity (P = 0.002 and r = 0.43) and global strain (GLS) (P = 0.000 and r = 0.60) were significantly associated with T2*. A GLS < 19.5 could predict a T2* level below 20 by 82.14% sensitivity and 86.36% specificity (area under the curve = 0.87; p < 0.0001).

Conclusion

While serum ferritin level and ejection fraction are not useful candidates, GLS may be used as a valuable marker to screen thalassemia patients for myocardial iron deposition, using a cut off value below − 19.5. This approach may facilitate the cardiac follow up, reduce the costs, and contribute to preventing deterioration of cardiac function in countries with limited availability of cardiac MRI.
The first case of gland inclusion in an intrapulmonary lymph node: a mimic of metastasis
Authors: Wang Chenglong , Cao Yijia , Zeng Min , Wang Lijuan , Cao Xiaojing , Zou Lingfeng , Cao Youde
Published: November 2019

Background

Lymph node inclusions are foci of ectopic tissue in lymph nodes, which were reported in different areas of the body. However, inclusions in the mediastinal lymph node are rare. Here, we report the first case of glandular inclusion within the parenchyma of the intrapulmonary lymph node in a patient with primary lung adenocarcinoma.

Case presentation

A computed tomography (CT) scan showed a solid pulmonary nodule in the right upper lobe in a 44-year-old man. After a fine needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph dissection were performed. Histological sections of the lung demonstrated a papillary predominant adenocarcinoma and one intrapulmonary lymph node, which displayed glandular inclusion occupying the node parenchyma. The gland inclusion was very similar to metastasis, but was formed by two layers of epithelial cells, and the abluminal cells were positive for P63, P40, and CK5/6. The patient has remained alive without recurrence and metastasis at the last follow-up before publication.

Conclusions

It is very important to correctly diagnose a lymph node inclusion for proper clinical management.
Adherence to a healthy lifestyle and all-cause and cause-specific mortality in Chinese adults: a 10-year prospective study of 0.5 million people
Authors:   on behalf of the China Kadoorie Biobank Collaborative Group, Zhu Nanbo , Yu Canqing , Guo Yu , Bian Zheng , Han Yuting , Yang Ling , Chen Yiping , Du Huaidong , Li Huimei , Liu Fang , Chen Junshi , Chen Zhengming , Lv Jun , Li Liming
Published: November 2019

Background

Adherence to a healthy lifestyle is associated with substantially lower risks of mortality from all causes, cardiovascular diseases, and cancer in white populations. However, little is known about the health benefits among non-white populations. Also, no previous studies have focused on respiratory disease mortality in both white and non-white populations. We assessed the relationships between a combination of healthy lifestyle factors and multiple death outcomes in Chinese adults.

Methods

This study included 487,198 adults aged 30–79 years from the China Kadoorie Biobank without heart disease, stroke, and cancer at study enrolment. We defined five healthy lifestyle factors as never smoking or smoking cessation not due to illness; non-daily drinking or moderate alcohol drinking; median or higher level of physical activity; a diet rich in vegetables, fruits, legumes and fish, and limited in red meat; a body mass index of 18.5 to 27.9 kg/m2 and a waist circumference < 90 cm (men)/85 cm (women). Cox regression was used to produce adjusted hazard ratios (HRs) relating these healthy lifestyle factors to all-cause and cause-specific mortality.

Results

During a median follow-up of 10.2 years (IQR 9.2–11.1), we documented 37,845 deaths. After multivariable adjustment, the number of healthy lifestyle factors exhibited almost inverse linear relationships with the risks of all-cause and cause-specific mortality. Compared with participants without any healthy factors, the hazard ratio of participants with five healthy factors was 0.32 [95% confidence interval (CI): 0.28, 0.37] for all-cause mortality. The corresponding HRs in specific cause of death were 0.42 (95% CI: 0.26, 0.67) for ischaemic heart disease, 0.21 (95% CI: 0.09, 0.49) for ischaemic stroke, 0.37 (95% CI: 0.22, 0.60) for haemorrhage stroke, 0.36 (95% CI: 0.29, 0.45) for cancer, 0.26 (95% CI: 0.14, 0.48) for respiratory diseases, and 0.29 (95% CI: 0.22, 0.39) for other causes. Theoretically, 38.5% (95% CI: 33.0, 43.8%) of all-cause mortality was attributable to nonadherence to a healthy lifestyle, and the proportions of preventable deaths through lifestyle modification ranged from 26.9 to 47.9% for cause-specific mortality.

Conclusions

Adherence to a healthy lifestyle was associated with substantially lower risks of all-cause, cardiovascular, respiratory, and cancer mortality in Chinese adults. Promotion of a healthy lifestyle may considerably reduce the burden of non-communicable diseases in China.
Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis
Authors: Cruz-Herranz Andrés , Dietrich Michael , Hilla Alexander M. , Yiu Hao H. , Levin Marc H. , Hecker Christina , Issberner Andrea , Hallenberger Angelika , Cordano Christian , Lehmann-Horn Klaus , Balk Lisanne J. , Aktas Orhan , Ingwersen Jens , von Gall Charlotte , Hartung Hans-Peter , Zamvil Scott S. , Fischer Dietmar , Albrecht Philipp , Green Ari J.
Published: November 2019

Background

Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings.

Methods

Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35–55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35–55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139–151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment.

Results

Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35–55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35–55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy.

Conclusions

Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35–55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.
Giant virus vs amoeba: fight for supremacy
Authors: Oliveira Graziele , La Scola Bernard , Abrahão Jônatas
Published: November 2019

Since the discovery of mimivirus, numerous giant viruses associated with free-living amoebae have been described. The genome of giant viruses can be more than 2.5 megabases, and virus particles can exceed the size of many bacteria. The unexpected characteristics of these viruses have made them intriguing research targets and, as a result, studies focusing on their interactions with their amoeba host have gained increased attention. Studies have shown that giant viruses can establish host–pathogen interactions, which have not been previously demonstrated, including the unprecedented interaction with a new group of small viruses, called virophages, that parasitize their viral factories. In this brief review, we present recent advances in virophage–giant virus–host interactions and highlight selected studies involving interactions between giant viruses and amoebae. These unprecedented interactions involve the giant viruses mimivirus, marseillevirus, tupanviruses and faustovirus, all of which modulate the amoeba environment, affecting both their replication and their spread to new hosts.