bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of healthcare services among Chinese migrants in Kenya: a qualitative study
Authors: Qiu Jialing , Song Duo , Nie Juan , Su Mengyi , Hao Chun , Gu Jing , Hao Yuantao , Kiarie James N. , Chung Michael H.
Published: December 2019

Background

The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya.

Methods

Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes.

Results

Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care.

Conclusions

Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.
Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger
Authors: Coldiron Matthew E. , Assao Bachir , Langendorf Céline , Sayinzoga-Makombe Nathan , Ciglenecki Iza , de la Tour Roberto , Piriou Erwan , Yarima Bako Mahaman , Mumina Ann , Guindo Ousmane , Page Anne-Laure , Grais Rebecca F.
Published: December 2019

Background

Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative.

Methods

A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season.

Results

In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention.

Conclusions

The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
Malnutrition impairs mitochondrial function and leukocyte activation
Authors: Bañuls Celia , de Marañon Aranzazu M. , Veses Silvia , Castro-Vega Iciar , López-Domènech Sandra , Salom-Vendrell Christian , Orden Samuel , Álvarez Ángeles , Rocha Milagros , Víctor Víctor M. , Hernández-Mijares Antonio
Published: December 2019

Background

The aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population.

Methods

For this cross-sectional study, a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were evaluated.

Results

DRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group (p < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O2 consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1.

Conclusions

Our results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.
Molecular dynamics simulation of reversible electroporation with Martini force field
Authors: Zhou Cheng , Liu Kefu
Published: December 2019

Background

After the discovery of membrane-reversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology and medicine. The research on the basic mechanism has increasingly attracted attention. Although most research has focused on models that consider all atomic and molecular interactions and much atomic-level information can be obtained, the huge computational demand limits the models to simulations of only a few nanometers on the spatial scale and a few nanoseconds on the time scale. In order to more comprehensively study the reversible electroporation mechanism of phospholipid membrane on the nanoscale and at longer time intervals of up to 100 ns, we developed a dipalmitoylphosphatidylcholine (DPPC) phospholipid membrane model with the coarse-grained Martini force field. The model was tested by separately examining the morphology of the phospholipid membrane, the hydrophilic channel size, the distribution of the voltage potential on both sides of the membrane, and the movement of water molecules and ions during electroporation.

Results

The results showed that the process went through several stages: (1) the formation of the pore with defects originating on the surface. (2) The maintenance of the pore. The defects expanded to large pores and the size remains unchanged for several nanoseconds. (3) Pore healing stage due to self-assembly. Phospholipid membrane shrunk and the pore size decreased until completely closed. The pores were not circular in cross-section for most of the time and the potential difference across the membrane decreased dramatically after the pores formed, with almost no restoration of membrane integrity even when the pores started to close.

Conclusions

The mechanism of the reversible electroporation process on the nanoscale level, including defects, expansion, stability, and pore closing stages on a longer time scale of up to 100 ns was demonstrated more comprehensively with the coarse-grained Martini force field, which took both the necessary molecular information and the calculation efficiency into account.
Connecting knowledge with action for health equity: a critical interpretive synthesis of promising practices
Authors: Plamondon Katrina M. , Caxaj C. Susana , Graham Ian D. , Bottorff Joan L.
Published: December 2019

Connecting knowledge with action (KWA) for health equity involves interventions that can redistribute power and resources at local, national, and global levels. Although there is ample and compelling evidence on the nature, distribution, and impact of health inequities, advancing health equity is inhibited by policy arenas shaped by colonial legacies and neoliberal ideology. Effective progress toward health equity requires attention to evidence that can promote the kind of socio-political restructuring needed to address root causes of health inequities. In this critical interpretive synthesis, results of a recent scoping review were broadened to identify evidence-informed promising practices for KWA for health equity. Following screening procedures, 10 literature reviews and 22 research studies were included in the synthesis. Analysis involved repeated readings of these 32 articles to extract descriptive data, assess clarity and quality, and identify promising practices. Four distinct kinds of promising practices for connecting KWA for health equity were identified and included: ways of structuring systems, ways of working together, and ways of doing research and ways of doing knowledge translation. Our synthesis reveals that advancing health equity requires greater awareness, dialogue, and action that aligns with the what is known about the causes of health inequities. By critically reflecting on dominant discourses and assumptions, and mobilizing political will from a more informed and transparent democratic exercise, knowledge to action for health equity can be achieved.
Transcatheter MitraClip repair alters mitral annular geometry – device induced annular remodeling on three-dimensional echocardiography predicts therapeutic response
Authors: Kim Jiwon , Palumbo Maria Chiara , Khalique Omar K. , Rong Lisa Q. , Sultana Razia , Das Mukund , Jantz Jennifer , Nagata Yasfumi , Devereux Richard B. , Wong Shing Chiu , Bergman Geoffrey W. , Levine Robert A. , Ratcliffe Mark B. , Weinsaft Jonathan W.
Published: December 2019

Background

Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain.

Methods

The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE.

Results

Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p < 0.01). In multivariate analysis, sub-optimal MitraClip response was independently associated with larger pre-procedural mitral annular area on 3D TEE (OR 1.93 per cm2/m2 [CI 1.19–3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02–1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95–30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p < 0.001) as well as mitral tenting height, area, and volume (all p < 0.05): Magnitude of MitraClip induced reductions in mitral annular circumference on intra-procedural 3D TEE was greater among patients with, compared to those without, sub-optimal MitraClip response (>mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028).

Conclusions

MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.
Coexistence of aortic valve stenosis and cardiac amyloidosis: echocardiographic and clinical significance
Authors: Peskó Gergely , Jenei Zsigmond , Varga Gergely , Apor Astrid , Vágó Hajnalka , Czibor Sándor , Prohászka Zoltán , Masszi Tamás , Pozsonyi Zoltán
Published: December 2019

Background

Left ventricular hypertrophy and diastolic dysfunction are common echocardiographic features of both aortic valve stenosis (AS) and cardiac amyloidosis (CA). These two different entities therefore may mask each other. From recent years, there is a growing body of evidence about the relatively high incidence of wild-type transthyretin (wtTTR) amyloidosis in AS, but there are scarce data on the prevalence of AS in CA, particularly in AL-type amyloidosis. The echocardiographic approach to these patients is not obvious, and not evidence based. We aimed to study the prevalence, severity, and type of AS in patients with CA and also to evaluate the potential of echocardiography in the diagnostic process.

Methods

Between January 2009 and January 2019, we retrospectively analyzed the clinical and echocardiographic data, and the echocardiographic work up of 55 consecutive CA patients.

Results

80% of our CA patients had AL amyloidosis. We identified 5 patients (9%) with moderate to severe AS: two with moderate AS and three with low-flow, low-grade AS (LFLG AS). Further analysis of the latter three patients with dobutamine stress echocardiography revealed pseudo-severe LFLG AS in two, and true-severe AS in one patient.

Conclusion

The prevalence of moderate to severe AS is 9% in our population of CA patients, the majority of whom have AL amyloidosis. Dobutamine echocardiography seems to be appropriate for the further characterization of patients with LFLG AS, even with normal ejection fraction.
Perceived need, barriers to and facilitators of mental health care among HIV-infected PWID in Hanoi, Vietnam: a qualitative study
Authors: Nguyen Minh X. , Go Vivian F. , Bui Quynh X. , Gaynes Bradley N. , Pence Brian W.
Published: December 2019

Background

The HIV epidemic in Vietnam has been primarily driven by injection drug use. HIV-infected people who inject drugs (PWID) in Vietnam have very high rates of mental health problems, which can accelerate progression to AIDS and increase mortality rates. No research has explored the barriers and facilitators of mental health care for HIV-infected PWID in Vietnam.

Methods

We conducted 28 in-depth interviews among HIV-infected PWID (n= 16), HIV and MMT (methadone maintenance treatment) providers (n= 8), and health officials (n= 4) in Hanoi. We explored participants’ perceptions of mental health disorders, and barriers and facilitators to seeking and receiving mental health care.

Results

HIV-infected PWID were perceived by both PWID, HIV/MMT providers, and health officials to be vulnerable to mental health problems and to have great need for mental health care. Perceived social, physical, and economical barriers included stigma towards HIV, injection drug use, and mental illnesses; lack of awareness around mental health issues; lack of human resources, facilities and information on mental health services; and limited affordability of mental health services. Social support from family and healthcare providers was a perceived facilitator of mental health care.

Conclusions

Interventions should raise self-awareness of HIV-infected PWID about common mental health problems; address social, physical, economic barriers to seeking mental health services; and increase social support for patients.
The outcomes of isolated ureteral resection and reconstruction in non-urologic cancer patients who underwent cytoreductive surgery (CRC) and hyperthermic intraperitoneal chemotherapy (HIPEC)
Authors: Morkavuk Şevket Barış , Güner Murat , Tez Mesut , Ünal Ali Ekrem
Published: December 2019

Background

Urinary system resections are performed during the cytoreductive surgery with hypertermic intraperitoneal chemotherapy (CRS-HIPEC). However, isolated ureter resection and reconstruction results are uncertain. The aim of this study was to evaluate the postoperative outcomes of isolated ureteral resection and reconstructions in patients who underwent CRC and HIPEC procedure.

Methods

A total of 257 patients that underwent CRC and HIPEC between 2015 and 2017 in the Department of Surgical Oncology, Faculty of Medicine, Ankara University, were retrospectively analyzed. Twenty patients that had undergone isolated ureteral resection and reconstruction were included in the study. Predisposing factors were investigated in patients who developed postoperative complications.

Results

The mean age of the patients was 55.1 years. The mean follow-up time of all the patients was 11.6 months. Postoperative mortality occurred in two patients. The mean PCI score was 13.9. Postoperative urologic complications were observed in eight patients after ureter reconstruction. There was no statistically significant difference between the groups in terms of reconstruction techniques and postoperative complications (P = 302). There was no correlation between age (P = 0.571) and gender (P = 0.161) with complications. CRS-HIPEC was performed mostly due to gynecologic malignancy. However, there was no correlation between the primary cancer diagnosis and the development of complications (P = 0.514). The hospital stay duration was higher in the group with complications (16.3 vs 8.8 days, P = 0.208).

Conclusions

Ureteral resections and reconstructions can be performed for R0/1 resections in CRS-HIPEC operations. It leads to an increase in hospital stay. But there is no significant difference in the development of complications. In the management of complications, conservative approach was sufficient.
Pathological complete response by advanced hepatocellular carcinoma with massive macrovascular invasion to hepatic arterial infusion chemotherapy: a case report
Authors: Sano Shusei , Nakata Shinji , Wada Shuichi , Kuroiwa Masatsugu , Sakai Hiroki , Kusama Kei , Machida Taiichi , Nishio Akihito , Ito Ichiro , Sodeyama Harutsugu
Published: December 2019

Background

Advanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response.

Case presentation

A 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence.

Conclusions

HAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.
Violence against health care workers in China, 2013–2016: evidence from the national judgment documents
Authors: Cai Ruilie , Tang Ji , Deng Chenhui , Lv Guofan , Xu Xiaohe , Sylvia Sean , Pan Jay
Published: December 2019

Background

Incidents of patient-initiated workplace violence against health care workers have been a subject of substantial public attention in China. Patient-initiated violence not only represents a risk of harm to health care providers but is also indicative of general tensions between doctors and patients which pose a challenge to improving health system access and quality. This study aims to provide a systematic, national-level characterization of serious workplace violence against health care workers in China.

Methods

This study extracted data from the China Judgment Online System, a comprehensive database of judgment documents. Three key phrases, “criminal case,” “health care institution,” and “health care worker” were used to search the China Judgment Online System for relevant cases between January 1, 2013, and December 31, 2016. Data extracted from identified cases was used to document the occurrence, the degree of risk, and the factors associated with serious workplace violence.

Results

In total, 459 criminal cases involving patient-initiated workplace violence against health care workers in China were reported and processed. The analysis revealed geographic heterogeneity in the occurrence of serious workplace violence, with lower incidence in western provinces compared to central and eastern provinces. Primary hospitals experienced the highest rates of serious workplace violence and emergency departments and doctors were at higher risk compared with other departments and health workers. Perpetrators were primarily male farmers aged 18 to 44 with low levels of education. The most frequently reported reasons of serious patient-initiated workplace violence included perceived medical malpractice by the perpetrator after the death of a patient, death of a patient with no other reason given, failures of the compensation negotiations after the death of a patient, and dissatisfaction with the treatment outcomes.

Conclusions

Serious workplace violence against providers varies across regions and types of health care institutions in China. Perception of low-quality care is the most reported reason for violence. Efforts should be made to improve quality of care in the low-level health institutions and strengthen the doctor-patient communication during the whole course of service.
Utilisation of evidence from Thailand’s National Health Examination Survey in policy development: finding the weakest link
Authors: Tantivess Sripen , Yothasamut Jomkwan , Saengsri Wilailak
Published: December 2019

Background

Health surveillance and survey data are helpful in evidence-informed policy decisions. This study is part of an evaluation of the National Health Examination Survey (NHES) programme in Thailand. This paper focuses on the obstacles in the translation of survey information into policies at a national level.

Methods

In-depth interviews with relevant individuals and representatives of institutes were carried out for the data collection. A total of 26 focal informants included executives and staff of NHES funders, government health agencies, civil society organisations, health experts, NHES programme managers and researchers in the survey network.

Results

Utilisation of NHES data in policy-making is limited for many reasons. Despite the potential users’ positive views on the technical integrity of experts and practitioners involved in the NHES, the strength of employing health examinations in the data collection is not well recognised. Meanwhile, alternative health surveillance platforms that offer similar information on a shorter timescale are preferable in policy monitoring and evaluation. In sum, the lack of governance of Thailand’s health surveillance system is identified as a key element hindering the translation of health surveys, including the NHES, into policies.

Conclusion

Despite an adequate capacity to conduct population health surveys, the lack of governance structure and function has resulted in a fragmented health monitoring system. Large and small survey projects are conducted and funded by different institutes without common policy direction and alignment mechanisms for prioritising survey topics, collective planning and capacity-building programmes for survey practitioners and users. Lessons drawn from Thailand’s NHES can be helpful for policy-makers in other low- and middle-income countries, as effective governance for evidence generation and utilisation is necessary in all contexts, regardless of income level and available resources.
A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
Authors: Mirandola Leonardo , Chiriva-Internati Maurizio , Bresalier Robert , Piccotti Lucia , Grizzi Fabio , Marincola Francesco M.
Published: December 2019

Background

The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and
presented in the right context.

Methods

We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients.

Results

We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3+ T-reg cells in vitro.

Conclusions

This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients.
A spontaneously metastatic model of bladder cancer: imaging characterization
Authors: Tatum James L. , Kalen Joseph D. , Jacobs Paula M. , Ileva Lilia V. , Riffle Lisa A. , Hollingshead Melinda G. , Doroshow James H.
Published: December 2019

Background

Spontaneously metastatic xenograft models of cancer are infrequent and the few that exist are resource intensive. In xenografts, caliper measurements can be used to determine primary tumor burden and response to therapy but in metastatic disease models determination of the presence of metastatic disease, metastatic burden, and response to therapy are difficult, often requiring serial necropsy. In this study we characterized the development of visceral metastases in a patient derived xenograft model (PDXM) using in vivo imaging.

Results

We identified and characterized the previously unreported development of spontaneous liver and bone metastasis in a known patient derived xenograft, bladder xenograft BL0293F, developed by Jackson Laboratories and the University of California at Davis and available from the National Cancer Institute Patient-Derived Models Repository [1]. Among FDG-PET/CT, contrast-enhanced MRI and non-contrast MRI, non-contrast T2w MRI was the most effective and efficient imaging technique. On non-contrast T2 weighted MRI, hepatic metastases were observed in over 70% of animals at 52 days post tumor implantation without resection of the xenograft and in 100% of animals at day 52 following resection of the xenograft. In a group of animals receiving one cycle of effective chemotherapy, no animals demonstrated metastasis by imaging, confirming the utility of this model for therapy evaluation. There was good agreement between pathologic grade and extent of involvement observed on MRI T2w imaging.

Conclusion

PDX BL0293F is a reliable visceral organ (liver) metastatic model with high penetrance in both non-aggravated and post excisional situations, providing a reliable window for therapy intervention prior to required excision of the xenograft. The imaging characteristics of this model are highly favorable for non-clinical research studies of metastatic disease when used in conjunction with non-contrast T2 weighted MRI.
The potassium channel KCa3.1 represents a valid pharmacological target for microgliosis-induced neuronal impairment in a mouse model of Parkinson’s disease
Authors: Lu Jia , Dou Fangfang , Yu Zhihua
Published: December 2019

Background

Recent studies described a critical role for microglia in Parkinson’s disease (PD), where these central nerve system resident immune cells participate in the neuroinflammatory microenvironment that contributes to dopaminergic neurons loss in the substantia nigra. Understanding the phenotype switch of microgliosis in PD could help to identify the molecular mechanism which could attenuate or delay the progressive decline in motor function. KCa3.1 has been reported to regulate the “pro-inflammatory” phenotype switch of microglia in neurodegenerative pathological conditions.

Methods

We here investigated the effects of gene deletion or pharmacological blockade of KCa3.1 activity in wild-type or KCa3.1−/−mice after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mouse model of PD. MPTP-induced PD mouse model was subjected to the rotarod test to evaluate the locomotor ability. Glia activation and neuron loss were measured by immunostaining. Fluo-4 AM was used to measure cytosolic Ca2+level in 1-methyl-4-phenylpyridinium (MPP+)-induced microgliosis in vitro.

Results

We report that treatment of MPTP-induced PD mouse model with gene deletion or pharmacological blockade of KCa3.1 with senicapoc improves the locomotor ability and the tyrosine hydroxylase (TH)-positive neuron number and attenuates the microgliosis and neuroinflammation in the substantia nigra pars compacta (SNpc). KCa3.1 involves in store-operated Ca2+entry-induced Ca2+overload and endoplasmic reticulum stress via the protein kinase B (AKT) signaling pathway during microgliosis. Gene deletion or blockade of KCa3.1 restored AKT/mammalian target of rapamycin (mTOR) signaling both in vivo and in vitro.

Conclusions

Taken together, these results demonstrate a key role for KCa3.1 in driving a pro-inflammatory microglia phenotype in PD.
Supporting breastfeeding: Tanzanian men’s knowledge and attitude towards exclusive breastfeeding
Authors: Bulemela Janeth , Mapunda Heka , Snelgrove-Clarke Erna , MacDonald Noni , Bortolussi Robert
Published: December 2019

Background

Exclusive breastfeeding (EBF) is one of the key strategies to ensure infants and young children survive and grow. However, a 2010 study showed that it was only practiced by 50% of Tanzanian women. That study also found that men were rarely supportive; either at home or in the health facilities, due to their personal beliefs or to traditional beliefs and culture of the community. In a report six years later the rate of EBF has decreased to 30%, in one region.

Methods

In this qualitative study, we used focus groups to assess the knowledge and attitudes of 35 men from three villages on the benefits of EBF, the disadvantages of not breastfeeding, and how they can support their partners’ breastfeeding. In addition, we assessed how they felt about spending time at home, if they considered handling the infant to be rewarding and whether they helped the mother with home chores. Differences in village infrastructure and characteristics were noted.

Results

Five themes were identified, including traditional roles, and feelings of exclusion/inclusion and resistance. Men felt they needed better information on EBF. They wished that their partners could breastfeed for a longer time, since they realized it improved infant growth and prevented disease; however, they did not have time to remain with the infant at home. Poverty required the men to work for long periods outside the home. As well, the men were not involved with the Reproductive Child Health Clinic (RCHC) except at the time of delivery or for mandatory HIV testing, however, they wanted to be educated together with their partners at the RCHC.

Conclusion

Most men in this study understood that the EBF period was important, and that it broadened their relationship with their partner. EBF, however, could be a challenge for couples because of poverty. Nevertheless, many men wanted to help and to become more involved.
Virus-induced gene silencing (VIGS) in Cannabis sativa L.
Authors: Schachtsiek Julia , Hussain Tajammul , Azzouhri Khadija , Kayser Oliver , Stehle Felix
Published: December 2019

Background

The raised demand of cannabis as a medicinal plant in recent years led to an increased interest in understanding the biosynthetic routes of cannabis metabolites. Since there is no established protocol to generate stable gene knockouts in cannabis, the use of a virus-induced gene silencing (VIGS) method, resulting in a gene knockdown, to study gene functions is desirable.

Results

For this, a computational approach was employed to analyze theCannabis sativaL. transcriptomic and genomic resources. Reporter genes expected to give rise to easily scorable phenotypes upon silencing, i.e. thephytoene desaturase(PDS) andmagnesium chelatase subunit I(ChlI), were identified inC. sativa.Subsequently, the targets of specific small interfering RNAs (siRNAs) and silencing fragments were predicted and tested in a post-transcriptional gene silencing (PTGS) approach.Here we show for the first time a gene knockdown inC. sativausing theCotton leaf crumple virus(CLCrV) in a silencing vector system. Plants transiently transformed with theAgrobacterium tumefaciensstrain AGL1, carrying the VIGS-vectors, showed the desired phenotypes, spotted bleaching of the leaves. The successful knockdown of the genes was additionally validated by quantitative PCR resulting in reduced expression of transcripts from 70 to 73% forChlIandPDS, respectively. This is accompanied with the reduction of the chlorophyll a and carotenoid content, respectively. In summary, the data clearly demonstrate the potential for functional gene studies in cannabis using theCLCrV-based vector system.

Conclusions

The applied VIGS-method can be used for reverse genetic studies inC. sativato identify unknown gene functions. This will gain deeper inside into unknown biosynthetic routes and will help to close the gap between available genomic data and biochemical information of this important medicinal plant.
An efficient RGB-UAV-based platform for field almond tree phenotyping: 3-D architecture and flowering traits
Authors: López-Granados Francisca , Torres-Sánchez Jorge , Jiménez-Brenes Francisco M. , Arquero Octavio , Lovera María , de Castro Ana I.
Published: December 2019

Background

Almond is an emerging crop due to the health benefits of almond consumption including nutritional, anti-inflammatory, and hypocholesterolaemia properties. Traditional almond producers were concentrated in California, Australia, and Mediterranean countries. However, almond is currently present in more than 50 countries due to breeding programs have modernized almond orchards by developing new varieties with improved traits related to late flowering (to reduce the risk of damage caused by late frosts) and tree architecture. Almond tree architecture and flowering are acquired and evaluated through intensive field labour for breeders. Flowering detection has traditionally been a very challenging objective. To our knowledge, there is no published information about monitoring of the tree flowering dynamics of a crop at the field scale by using color information from photogrammetric 3D point clouds and OBIA. As an alternative, a procedure based on the generation of colored photogrammetric point clouds using a low cost (RGB) camera on-board an unmanned aerial vehicle (UAV), and an semi-automatic object based image analysis (OBIA) algorithm was created for monitoring the flower density and flowering period of every almond tree in the framework of two almond phenotypic trials with different planting dates.

Results

Our method was useful for detecting the phenotypic variability of every almond variety by mapping and quantifying every tree height and volume as well as the flowering dynamics and flower density. There was a high level of agreement among the tree height, flower density, and blooming calendar derived from our procedure on both fields with the ones created from on-ground measured data. Some of the almond varieties showed a significant linear fit between its crown volume and their yield.

Conclusions

Our findings could help breeders and researchers to reduce the gap between phenomics and genomics by generating accurate almond tree information in an efficient, non-destructive, and inexpensive way. The method described is also useful for data mining to select the most promising accessions, making it possible to assess specific multi-criteria ranking varieties, which are one of the main tools for breeders.
Detection of white head symptoms of panicle blast caused by Pyricularia oryzae using cut-flower dye
Authors: Hayashi Keiko , Yoshida Tomofumi , Hayano-Saito Yuriko
Published: December 2019

Background

Breeding of rice with panicle resistance to rice blast disease caused by Pyricularia oryzae is a challenge towards sustainable rice production. Methods for accurate estimation of disease severity can support breeding. White head symptoms are a commonly used index of panicle blast in the field. As the development mechanism of this symptom remains unclear, we used cut-flower dye (CFD) solution to visualize the infected panicle tissues.

Results

CFD delineated the edge of white head symptoms in rice panicles artificially infected with P. oryzae. Hyphae within the tissues were confirmed through staining with a fluorescent wheat germ agglutinin conjugate. Hyphal density was obviously diminished at the dye edge. Growing hyphae preferred to move along the vascular bundles; infected tissues lost the ability to transport water, leading to white head formation. By marking the edge of the white heads, this simple dyeing technique precisely reveals the extent of infection. Further, digital imaging allowed dried samples to be stored and reassessed later.

Conclusions

The CFD detection technique served as a powerful tool for estimating disease severity by color, as it clearly revealed lesions in both the panicles and leaves. Combined with reliable methods for artificial inoculation and observation of infecting hyphae, this technique will advance the research and breeding of panicle blast-resistant rice.
Retinal hyperreflective foci in Fabry disease
Authors: Atiskova Yevgeniya , Rassuli Rahman , Koehn Anja Friederike , Golsari Amir , Wagenfeld Lars , du Moulin Marcel , Muschol Nicole , Dulz Simon
Published: December 2019

Background

Fabry disease (FD) is an X-linked inherited storage disorder caused by deficiency of lysosomal alpha-Galactosidase A. Here we describe new retinal findings in patients with FD assessed by Spectral domain optical coherence tomography (SD-OCT) and their possible clinical relevance.

Methods

54 eyes of 27 FD patients and 54 eyes of 27 control subjects were included. The ophthalmic examination included visual acuity testing, tonometry, slit lamp and fundus examination. SD-OCT imaging of the macula was performed in all subjects. Central retinal thickness and retinal nerve fiber layer analysis were quantified. Vessel tortuosity was obtained by a subjective scoring and mathematically calculated. Inner retinal hyperreflective foci (HRF) were quantified, clinically graded and correlated with a biomarker of Fabry disease (lyso-Gb3).

Results

In comparison to an age-matched control group, a significant amount of HRF was identified in macular SD-OCT images in FD patients. These HRF were localized within the inner retinal layers. Furthermore, lyso-Gb3 levels correlated significantly with the quantitative evaluation of HRF (p < 0,001). In addition, the vessel tortuosity was remarkably increased in FD patients compared to control persons and correlated significantly with lyso-G3 levels (p = 0.005). A further subanalysis revealed significantly higher HRF and vessel tortuosity scores in male patients with the classic FD phenotype.

Conclusions

The observational, cross sectional, comparative study describes novel intraretinal findings in patients with FD. We were able to identify suspicious HRF within the inner retinal layers. These findings were not accompanied by functional limitations, as visual acuity remained unchanged. However, HRF correlated well with lyso-Gb3, a degradation product of the accumulating protein Gb3 and might potentially indicate Gb3 accumulation within the highly metabolic and densely vascularized macula.
Safety of antithrombotic therapy in subjects with hereditary hemorrhagic telangiectasia: prospective data from a multidisciplinary working group
Authors:   on behalf of the Multidisciplinary Gemelli Group for HHT, Gaetani Eleonora , Agostini Fabiana , Porfidia Angelo , Giarretta Igor , Feliciani Daniela , Di Martino Luigi , Tortora Annalisa , Gasbarrini Antonio , Pola Roberto
Published: December 2019

Subjects with the rare autosomal dominant disease Hereditary Hemorrhagic Telangiectasia (HHT) may develop medical conditions that require antithrombotic therapy (AT). However, safety of AT is uncertain in these patients and the only data currently available derive from retrospective analyses of registries and/or databases. At the HHT Centre of the ‘Fondazione Policlinico Universitario A. Gemelli IRCCS’ (Rome, Italy), a prospective study is currently ongoing to evaluate the safety of AT in subjects affected by HHT. The study is enrolling subjects with a definite diagnosis of HHT who receive an AT prescription by one of the physicians of the HHT Centre. The primary outcome is the number of hemorrhagic events, distinguished in major, clinically relevant non-major (CRNM), and minor bleedings, according to the criteria of the International Society on Thrombosis and Hemostasis (ISTH). Another primary outcome is worsening of epistaxis upon initiation of AT, assessed using the internationally accepted Epistaxis Severity Score (ESS). Additional outcomes are changes in hemoglobin levels and changes in the need of blood transfusion after initiation of AT. Here, we present the results of an interim analysis, conducted on the 12 HHT subjects that have been enrolled so far. After a mean follow-up of 6.5 ± 0.8 months, no major bleedings, no CRNM bleedings, and no minor bleedings different from epistaxis were recorded. Worsening of epistaxis upon initiation of AT was documented only in one patient, but did not require discontinuation of AT. There were no significant changes in the mean ESS measured before and after initiation of AT. There were no significant changes in hemoglobin levels and need for blood transfusion after initiation of AT. Although preliminary, these are the first prospective data on the safety of AT in HHT patients. Our interim analysis suggests that, when prescribed by experienced physicians in a multidisciplinary setting, AT is well tolerated by HHT patients. More patients and a longer follow-up are needed to confirm these findings.
Anxiolytic effects of the flavonoid luteolin in a mouse model of acute colitis
Authors: Gadotti Vinicius M. , Zamponi Gerald W.
Published: December 2019

Anxiety related disorders commonly occur in association with major depressive disorder (MDD) in individuals suffering from peripheral inflammation, with a higher prevalence among IBS patients. We have previously shown that the bioflavonoid luteolin has pronounced analgesic and antidepressant-like effects in mice with dextran sodium sulfate (DSS)-induced colitis. Here, we further evaluate the biological effect of luteolin as a possible anxiolytic agent in DSS treated mice. Anxiolytic action was evaluated using the open field test (OF), the novelty suppressed feeding test (NSFT) and the elevated plus maze test (EPM). Luteolin increased the number of crossings in the center of the OF apparatus, reduced the latency to interact with the food pellet in the NSFT, and increased the time spent in the open arms in the EPM. These results suggest luteolin as a possible natural anxiolytic molecule without sedative effects, thus reinforcing its therapeutic potential for the comorbidities involving peripheral inflammation, pain, mood and anxiety-related disorders.