bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical practice guideline palliative care for children and other strategies to enhance shared decision-making in pediatric palliative care; pediatricians’ critical reflections
Authors: Dreesens Dunja , Veul Lotte , Westermann Jonne , Wijnands Nicole , Kremer Leontien , van der Weijden Trudy , Verhagen Eduard
Published: November 2019

Background

Because of practice variation and new developments in palliative pediatric care, the Dutch Association of Pediatrics decided to develop the clinical practice guideline (CPG) palliative care for children. With this guideline, the association also wanted to precipitate an attitude shift towards shared decision-making (SDM) and therefore integrated SDM in the CPG Palliative care for children. The aim was to gain insight if integrating SDM in CPGs can potentially encourage pediatricians to practice SDM. Its objectives were to explore pediatricians’ attitudes and thoughts regarding (1) recommendations on SDM in CPGs in general and the guideline Palliative care for children specifically; (2) other SDM enhancing strategies or tools linked to CPGs.

Methods

Semi-structured face-to-face interviews. Pediatricians (15) were recruited through purposive sampling in three university-based pediatric centers in the Netherlands. The interviews were audio-recorded and transcribed verbatim, coded by at least two authors and analyzed with NVivo.

Results

Some pediatricians considered SDM a skill or attitude that cannot be addressed by clinical practice guidelines. According to others, however, clinical practice guidelines could enhance SDM. In case of the guideline Palliative care for children, the recommendations needed to focus more on how to practice SDM, and offer more detailed recommendations, preferring a recommendation stating multiple options. Most interviewed pediatricians felt that patient decisions aids were beneficial to patients, and could ensure that all topics relevant to the patient are covered, even topics the pediatrician might not consider him or herself, or deems less important. Regardless of the perceived benefit, some pediatricians preferred providing the information themselves instead of using a patient decision aid.

Conclusions

For clinical practice guidelines to potentially enhance SDM, guideline developers should avoid blanket recommendations in the case of preference sensitive choices, and SDM should not be limited to recommendations on non-treatment decisions. Furthermore, preference sensitive recommendations are preferably linked with patient decision aids.
Crimes by people with schizophrenia in Korea: comparison with the general population
Authors: Kim Agnus M.
Published: November 2019

Background

This study was performed to describe the prevalence of crimes committed by persons with schizophrenia using population-based data and to compare the crime prevalence of persons with schizophrenia and the general population.

Methods

The number of crimes was obtained from the Korean National Police Agency (KNPA) crime statistics (2012–2016), which provide the number of crimes in terms of the criminal’s mental status and mental health conditions. For the number of persons with schizophrenia, estimates were used which had been calculated from the inpatient and outpatient claims from the National Health Insurance Service. The crime prevalence in persons with schizophrenia was calculated according to the types of crimes, and a comparison with the general population was conducted.

Results

The overall crime prevalence of persons with schizophrenia was 72.7 to 90.3 per 10,000 from 2012 through 2016, which was about one fifth that of the general population. While the crime rates of the persons with schizophrenia were lower than the general population in most types of crimes including violence, intellectual crimes, and theft, the prevalence of murder, arson, and drug-related crimes in persons with schizophrenia was about five times, six times, and two times that of the general population respectively.

Conclusion

The higher prevalence of serious offences among persons with schizophrenia suggests the need for closer and more appropriate care for the population, which would be achieved through effective continuity of institutional and community care.
Perceived risk versus objectively measured risk of HIV acquisition: a cross-sectional study among HIV-negative individuals in Serodiscordant partnerships with clients attending an Urban Clinic in Uganda
Authors: Tugume Lillian , Muwonge Timothy Ronald , Joloba Edith Nakku , Isunju John Bosco , Kiweewa Flavia Matovu
Published: November 2019

Background

Acceptability of Pre-exposure Prophylaxis (PrEP) could be hampered by low self-perceived risk for HIV acquisition. Moreover, discordance between risk perception and actual risk of HIV acquisition is likely to occur. We assessed congruence between the level of self- perceived and that of objectively scored risk of HIV acquisition among HIV-negative individuals in discordant relationships.

Methods

This was a cross-sectional study among a representative sample of HIV-negative adult males and females whose partners were receiving antiretroviral therapy for at least 3 months from the Infectious Diseases Institute Clinic in Kampala, Uganda. Perceived risk was measured based on self-report using a numerical rating scale whereas objective risk was measured using a validated risk score tool. Congruence between perceived risk and objectively scored risk was evaluated using descriptive statistics and validity measures. Incongruence between the two phenomena was further evaluated using univariate and multivariate regression analyses.

Results

HIV-negative partners evaluated in this study were mostly male (64%) with a median age of 41 years (IQR 35 to 50). Majority (76.3%) of the partners perceived themselves as low risk for HIV acquisition. Similarly, most (93.8%) were objectively scored as low risk. However, nearly three quarters (72.7%) of partners who were objectively scored as high risk perceived themselves as being at low risk and all were men. The sensitivity and specificity of perceived risk for detecting the objectively measured risk was 27.3 and 76.5% respectively; area under ROC curve = 0.52; 95%CI (0.38, 0.66). The proportion of participants at high risk of HIV acquisition who perceived their risk as low was greater among those whose partners had detectable viral load compared to participants whose partners had undetectable viral load (PR = 0.51; 95%CI 0.29 to 0.90).

Conclusion

Incongruence between perceived and objectively measured risk of HIV acquisition does occur especially among individuals whose partners had a detectable viral load. PrEP counselling for serodiscordant couples should focus on explaining the consequence of detectable viral load in the HIV-positive partner on HIV transmission risk.
Determinants of treatment in patients with stage IV renal cell carcinoma
Authors: Hollenbeak Christopher S. , Schaefer Eric W. , Doan Justin , Raman Jay D.
Published: November 2019

Background

Advances in systemic targeted therapies afford treatment opportunities in patients with metastatic renal cell carcinoma (RCC). Elderly patients with metastatic RCC present a subpopulation for consideration owing to competing causes of mortality and benefits seen with new therapeutic agents. We investigate treatment patterns for elderly patients with stage IV RCC and determine factors associated with not receiving treatment.

Methods

The Surveillance Epidemiology and End Results (SEER) Medicare linked data set contained 949 stage IV RCC patients over age 65 diagnosed between 2007 and 2011. Treatment approach was modeled using multinomial logistic regression. Landmark analysis at 6 months accounted for early death as a potential explanation for no treatment.

Results

Of the 949 patients with stage IV RCC, 26.2% received surgery and 34.1% received systemic therapy within 6 months of diagnosis. Among our entire cohort, over half (51.2%) had no evidence of receiving surgery or systemic therapy. Among the 447 patients who survived at least 6 months, 26.6% did not receive treatment during this time. Older patients and those with a higher Charlson Comorbidity Index (CCI) had lower odds of being treated with surgery, systemic therapy, or both. Conversely, married patients had higher odds of receiving these therapies. These associations were largely sustained in the 6-month landmark analyses.

Conclusions

Elderly patients with metastatic RCC present a unique subpopulation for consideration owing to competing causes of mortality. Many elderly patients with stage IV RCC did not receive surgery or systemic therapy up to 6 months from diagnosis. Several clinical and demographic factors were associated with this observation. Further investigation is needed to understand the rationale underlying the underutilization of systemic therapy in elderly patients.
Pharmacists’ knowledge, attitude and involvement in palliative care in selected tertiary hospitals in southwestern Nigeria
Authors: ADISA Rasaq , ANIFOWOSE Aderonke Tolulope
Published: November 2019

Background

The growing number of people living with life-limiting illness is a global health concern. This study therefore aimed to explore the involvement of pharmacists in selected tertiary hospitals in Nigeria in palliative care (PC). It also sought to evaluate their knowledge and attitude to PC as well as factors that hinder pharmacists’ participation in PC.

Method

Questionnaire-guided survey among pharmacists working in three-tertiary hospitals in southwestern Nigeria. The self-administered questionnaire comprised 18-item general knowledge questions related to PC, attitude statements with 5-point Likert-scale options and question-items that clarify extent of involvement in PC and barriers to participation. Overall score by pharmacists in the knowledge and attitude domains developed for the purpose of this study was assigned into binary categories of “adequate” and “inadequate” knowledge (score > 75% versus≤75%), as well as “positive” and “negative” attitude (ranked score > 75% versus≤75%), respectively. Descriptive statistics, Mann-Whitney-U and Kruskal-Wallis tests were used for analysis at p < 0.05.

Results

All the 110 pharmacists enrolled responded to the questionnaire, given a response rate of 100%. Overall, our study showed that 23(21.1%) had adequate general knowledge in PC, while 14(12.8%) demonstrated positive attitude, with 45(41.3%) who enjoyed working in PC. Counselling on therapy adherence (100;90.9%) was the most frequently engaged activity by pharmacists; attending clinical meetings to advise health team members (45;40.9%) and giving educational sessions (47;42.7%) were largely cited as occasionally performed duties, while patient home visit was mostly cited (60;54.5%) as a duty not done at all. Pharmacists’ unawareness of their need in PC (86;79.6%) was a major factor hindering participation, while pharmacists with PC training significantly felt more relaxed around people receiving PC compared to those without training (p = 0.003).

Conclusion

Hospital pharmacists in selected tertiary care institutions demonstrate inadequate knowledge, as well as negative attitude towards PC. Also, extent of involvement in core PC service is generally low, with pharmacists’ unawareness of their need in PC constituting a major barrier. Thus, a need for inclusion of PC concept into pharmacy education curriculum, while mandatory professional development programme for pharmacists should also incorporate aspects detailing fundamental principles of PC, in order to bridge the knowledge and practice gaps.
Antitumor and antioxidant effects of Clinacanthus nutans Lindau in 4 T1 tumor-bearing mice
Authors: Nik Abd Rahman Nik Mohd Afizan , Nurliyana M. Y. , Afiqah M. N. F. Natasha Nur , Osman Mohd Azuraidi , Hamid Muhajir , Lila Mohd Azmi Mohd
Published: November 2019

Background

Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice.

Methods

C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed.

Results

From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P < 0.05) and 1000 mg/kg (P < 0.05) showed a significant decrease in nitric oxide (NO) and malondialdehyde (MDA) levels in the blood. On the other hand, C. nutans extract (1000 mg/kg) also showed a significant decrease in the number of mitotic cells, tumor weight, and tumor volume. No inflammatory and adverse reactions related to splenocytes activities were found in all treated groups of mice. Despite its promising results, the concentration of both C. nutans extracts have also reduced the number of colonies formed in the liver and lungs.

Conclusion

In conclusion, C. nutans extracts exert antitumor and antioxidant activities against 4 T1 mouse breast model with no adverse effect and inflammatory response at high dose of 1000 mg/kg, indicating an effective and complementary approach for cancer prevention and treatment.
Ameliorative effects of aqueous extract of Forsythiae suspensa fruits on oxaliplatin-induced neurotoxicity in vitro and in vivo
Authors: Yi Jin-Mu , Shin Sarah , Kim No Soo , Bang Ok-Sun
Published: November 2019

Background

The dried fruits ofForsythia suspensahas generally been used to clear heat and detoxify in traditional Korean and Chinese medicine. Oxaliplatin is a first-line treatment chemotherapeutic agent for advanced colorectal cancer, but it induces peripheral neuropathy as an adverse side effect affecting the treatment regimen and the patient’s quality of life. The present study was conducted to evaluate the neuroprotective effects of an aqueous extract ofF. suspensafruits (EFSF) on oxaliplatin-induced peripheral neuropathy.

Methods

The chemical components from EFSF were characterized and quantified using the ultra-high performance liquid chromatography-diode array detector system. The cytotoxicities of anticancer drugs in cancer cells and PC12 cells were assessed by the Ez-Cytox viability assay. To measure the in vitro neurotoxicity, the neurite outgrowth was analyzed in the primary dorsal root ganglion (DRG) cells, and neural PC12 cells that were differentiated with nerve growth factor. To evaluate the in vivo neuroprotective activity, the von Frey test was performed in six-week-old male mice (C57BL/6) receiving EFSF (60–600 mg/kg) in the presence of 20–30 mg/kg cumulative doses of oxaliplatin. Thereafter, the mice were euthanized for immunohistochemical staining analysis with an antibody against PGP9.5.

Results

EFSF attenuated the cytotoxic activities of the various anticancer drugs in neural PC12 cells, but did not affect the anticancer activity of oxaliplatin in human cancer cells. Oxaliplatin remarkably induced neurotoxicities including cytotoxicity and the inhibited neurite outgrowth of DRG and neural PC12 cells. However, the co-treatment of EFSF (100 μg/ml) with oxaliplatin completely reversed the oxaliplatin-induced neurotoxicity. Forsythoside A, the major component of EFSF, also exerted remarkable neuroprotective effects against the oxaliplatin-induced neurotoxicity. In addition, EFSF (60–200 mg/kg) significantly alleviated the oxaliplatin-induced mechanical allodynia and loss of intra-epidermal nerve fiber to the levels of the vehicle control in the mouse peripheral neuropathy model.

Conclusions

EFSF could be considered a useful herbal medicine for the treatment of peripheral neuropathy in cancer patients receiving chemotherapy with oxaliplatin.
Effectiveness of electronic point-of-care reminders versus monthly feedback to improve adherence to 10 clinical recommendations in primary care: a cluster randomized clinical trial
Authors: Coma Ermengol , Medina Manuel , Méndez Leonardo , Hermosilla Eduardo , Iglesias Manuel , Olmos Carmen , Calero Sebastian
Published: November 2019

Background

Numerous studies have analyzed the effectiveness of electronic reminder interventions to improve different clinical conditions, and most have reported a small to moderate effect. Few studies, however, have analyzed reminder systems targeting multiple conditions, and fewer still have compared electronic point-of-care reminders systems with other forms of feedback designed to improve delivery of care.

Methods

We performed an unblinded cluster randomized clinical trial to compare the effectiveness of an electronic point-of-care reminder system with that of a well-established system providing monthly feedback on adherence to clinical recommendations. The control group received monthly feedback only while the intervention group received monthly feedback in addition to on-screen point-of-care reminders for 10 clinical conditions. The study targeted all physicians and nurses at the 283 primary care centers managed by the Institut Català de la Salut (approximately 6600 professionals).

Results

Following exclusions and randomization, 132 primary care centers (328,728 patients with reminders) were assigned to the intervention group while 137 centers (317,117 patients with reminders) were randomized to the control group. A 20.6% improvement (OR 1.29, 95% CI: 1.25–1.34) in reminder resolution rates was observed in the intervention group. Results varied according to the clinical condition. The most effective reminder was screening for diabetic retinopathy (OR 1.51, 95% CI:1.46–1.57) while the least effective reminders were measurement of glycated hemoglobin (OR: 1.10, 95% CI: 1.07–1.13) and smoking cessation encouragement (OR 1.12, 95% CI: 1.09–1.16).

Conclusions

Electronic point-of-care reminders were more effective than the existing monthly feedback system at resolving the 10 clinical situations. However, more studies are needed to investigate the variations of the effect observed.

Trial registration

Current Controlled TrialsISRCTN42391639, 08/10/2012. Retrospectively registered.
Development of nursing quality care process metrics and indicators for intellectual disability services: a literature review and modified Delphi consensus study
Authors: Doody Owen , Murphy Fiona , Lyons Rosemary , Gallen Anne , Ryan Judy , Downey Johanna , Sezgin Duygu
Published: November 2019

Background

Nursing process quality care metrics and indicators are quantifiable measures of the nursing care delivered to clients. They can be used to identify and support nurses’ contribution to high quality, safe, client care and are lacking in specialist intellectual disability nursing. In a national Nursing Quality Care-Metrics project for Irish intellectual disability services, a set of nursing quality care process metrics and associated indicators were established for intellectual disability services.

Methods

A two-stage design approach was undertaken; a broad scoping review of the literature and a modified Delphi consensus process. The Delphi included a four round e-Delphi survey and a consensus meeting. Four hundred one intellectual disability nurses working in Ireland were recruited for the surveys and 20 stakeholders attended the consensus meeting.

Results

From the review, 20 existing and 16 potential intellectual disability nursing metrics were identified for nurses to prioritise in the e-surveys. After the four survey rounds, 12 intellectual disability nursing metrics and 84 associated indicators were identified. Following the consensus meeting, these were reduced to 12 metrics and 79 indicators.

Conclusions

This first set of intellectual disability nursing process metrics and associated indicators has been identified for implementation in practice. These metrics while developed in Ireland have international relevance and their application and appropriateness in practice needs to be evaluated.
Short-term and long-term unintended impacts of a pilot reform on Beijing’s zero markup drug policy: a propensity score-matched study
Authors: Zeng Jianying , Chen Xiwen , Fu Hongqiao , Lu Ming , Jian Weiyan
Published: November 2019

Background

In September 2012, Beijing, the capital of China, selected five tertiary hospitals as pilots to remove the previously allowed 15% markup for drug sales. However, while most research demonstrated the significant decrease in drug sales, the core issue of high health expenditure was not well solved because of the unintended policy impact. This study aimed to empirically evaluate the short-term and long-term unintended impacts on controlling medical expenses of Beijing’s zero markup drug policy from 2012 to 2015.

Methods

This study extracted 2012–2015 individual-level data from the Beijing Urban Employee Basic Medical Insurance (UEBMI) database and performed a propensity score-matched analysis to evaluate the short-term and long-term impacts on controlling medical expenses. All inpatients in the 5 pilot reform hospitals were selected as the intervention group, while inpatients in other tertiary hospitals were selected as the control group.

Results

A total of 520,996 inpatients were extracted in this study. For patients in the pilot hospitals, the total expenditures per admission decreased from 17,140.3 yuan in 2012 to 15,430.1 yuan in 2013 and then increased to 16,789.8 yuan in 2015. Expenditure on drugs reduced from 5811.7 yuan in 2012 to 3903.4 yuan in 2015. However, a significant substitution effect of medical consumables was first observed in the third quarter of 2014, which undermined the impact of the policy. In the long-term, the intervention group and control group demonstrated the same trend.

Conclusions

After the zero markup drug policy, expenditure on drugs revealed a continuous decline. However, the decline in total expenditure was weakened by the substitution effect of medical consumables in the long term.
Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study
Authors: Wang Qin , Jokelainen Jari , Auvinen Juha , Puukka Katri , Keinänen-Kiukaanniemi Sirkka , Järvelin Marjo-Riitta , Kettunen Johannes , Mäkinen Ville-Petteri , Ala-Korpela Mika
Published: November 2019

Background

Insulin resistance (IR) is predictive for type 2 diabetes and associated with various metabolic abnormalities in fasting conditions. However, limited data are available on how IR affects metabolic responses in a non-fasting setting, yet this is the state people are mostly exposed to during waking hours in the modern society. Here, we aim to comprehensively characterise the metabolic changes in response to an oral glucose test (OGTT) and assess the associations of these changes with IR.

Methods

Blood samples were obtained at 0 (fasting baseline, right before glucose ingestion), 30, 60, and 120 min during the OGTT. Seventy-eight metabolic measures were analysed at each time point for a discovery cohort of 4745 middle-aged Finnish individuals and a replication cohort of 595 senior Finnish participants. We assessed the metabolic changes in response to glucose ingestion (percentage change in relative to fasting baseline) across the four time points and further compared the response profile between five groups with different levels of IR and glucose intolerance. Further, the differences were tested for covariate adjustment, including gender, body mass index, systolic blood pressure, fasting, and 2-h glucose levels. The groups were defined as insulin sensitive with normal glucose (IS-NGT), insulin resistant with normal glucose (IR-NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and new diabetes (NDM). IS-NGT and IR-NGT were defined as the first and fourth quartile of fasting insulin in NGT individuals.

Results

Glucose ingestion induced multiple metabolic responses, including increased glycolysis intermediates and decreased branched-chain amino acids, ketone bodies, glycerol, and triglycerides. The IR-NGT subgroup showed smaller responses for these measures (mean + 23%, interquartile 9–34% at 120 min) compared to IS-NGT (34%, 23–44%, P < 0.0006 for difference, corrected for multiple testing). Notably, the three groups with glucose abnormality (IFG, IGT, and NDM) showed similar metabolic dysregulations as those of IR-NGT. The difference between the IS-NGT and the other subgroups was largely explained by fasting insulin, but not fasting or 2 h glucose. The findings were consistent after covariate adjustment and between the discovery and replication cohort.

Conclusions

Insulin-resistant non-diabetic individuals are exposed to a similar adverse postprandial metabolic milieu, and analogous cardiometabolic risk, as those with type 2 diabetes. The wide range of metabolic abnormalities associated with IR highlights the necessity of diabetes diagnostics and clinical care beyond glucose management.
Determinants and extent of weight recording in UK primary care: an analysis of 5 million adults’ electronic health records from 2000 to 2017
Authors: Nicholson B. D. , Aveyard P. , Bankhead C. R. , Hamilton W. , Hobbs F. D. R. , Lay-Flurrie S.
Published: November 2019

Background

Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses.

Methods

A longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording.

Results

A total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38–42%) and GPs (37–39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6–8%) and health checks (6–7%), or were associated with consultations for contraception (5–8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed.

Conclusion

Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording.
The persistence of naturally acquired antibodies and memory B cells specific to rhoptry proteins of Plasmodium vivax in patients from areas of low malaria transmission
Authors: Kochayoo Piyawan , Changrob Siriruk , Wangriatisak Kittikorn , Lee Seong Kyun , Chootong Patchanee , Han Eun-Taek
Published: November 2019

Background

Rhoptries are the large, paired, secretory organelles located at the apical tip of the malaria merozoite that are considered important for parasite invasion processes.Plasmodium vivaxrhoptry proteins have been shown to induce humoral immunity during natural infections. Therefore, these proteins may be potential novel vaccine candidates. However, there is a lack of data on the duration of antibody and memory B cell (MBC) responses. Here, the longitudinal analysis of antibody and MBC responses to theP. vivaxrhoptry proteins PvRALP1-Ecto and PvRhopH2 were monitored and analysed in individuals to determine their persistence.

Methods

Thirty-nine samples fromP. vivax-infected subjects (age 18–60 years) were recruited to explore the frequency and persistence of antibody and MBC responses against rhoptry proteins (PvRALP1-Ecto and PvRhopH2) using both cross-sectional and longitudinal cohort study designs. Antibody levels were determined by ELISA during clinical malaria, and at 3, 9 and 12 months post-infection. The frequency of MBC sub-sets and presence of rhoptry-specific MBCs in subjects 18 months after treatment were detected by flow cytometry and ELISPOT assay.

Results

The seroprevalence of antibodies against PvRALP1-Ecto and PvRhopH2 proteins was found to be high during acute infection, with IgG1, IgG2 and IgG3 sub-classes predominant. However, these anti-rhoptry responses were short-lived and significantly decreased at 9 months post-infection. To relate the durability of these antibody responses to MBC persistence at post-infection, 18-month post-infection peripheral blood mononuclear cells (PBMCs) samples were taken to detect rhoptry-specific MBCs and frequency of MBC sub-sets, and correlate with antibody responses. These late post-infection samples revealed that rhoptry-specific MBCs were present in about 70% of total subjects. However, the persistence of specific MBCs was not correlated with antibody responses as the majority of malaria subjects who were positive for PvRALP1-Ecto- or PvRhopH2-specific MBCs were seronegative for the rhoptry antigens. The frequencies of classical MBCs were increased after infection, whereas those of activated and atypical MBCs were decreased, indicating that MBC responses could switch from activated or atypical MBCs to classical MBCs after parasite clearance, and were maintained in blood circulating at post-infection.

Conclusion

The study showed that rhoptry antigens induced the development and persistence of MBC responses inP. vivax-infected subjects who lived in a region of low malaria transmission, which were not related to the longevity of antibody responses.
The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection
Authors: Koch Marion , Cegla Jaimini , Jones Ben , Lu Yuning , Mallat Ziad , Blagborough Andrew M. , Angrisano Fiona , Baum Jake
Published: November 2019

Background

Malaria disease commences when blood-stage parasites, called merozoites, invade human erythrocytes. Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests erythrocyte biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties demanding its interrogation as a potential mediator of resistance to merozoite invasion of the erythrocyte.

Methods

Biophysical measurements of erythrocyte deformability by flicker spectroscopy were used to assess changes in erythrocyte bending modulus on forced integration of cholesterol and how these artificial changes affect invasion by humanPlasmodium falciparummerozoites. To validate these observations in a natural context, either murinePlasmodium bergheior humanPlasmodium falciparummerozoites were tested for their ability to invade erythrocytes from a hypercholesterolaemic mouse model or human clinical erythrocyte samples deriving from patients with a range of serum cholesterol concentrations, respectively.

Results

Erythrocyte bending modulus (a measure of deformability) was shown to be markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. In an in vitro infection context, however, erythrocytes taken from hypercholesterolaemic mice or from human clinical samples with varying serum cholesterol levels showed little difference in their susceptibility to merozoite invasion. Explaining this, membrane cholesterol levels in both mouse and human hypercholesterolaemia erythrocytes were subsequently found to be no different from matched normal serum controls.

Conclusions

Based on these observations, serum cholesterol does not appear to impact on erythrocyte susceptibility to merozoite entry. Indeed, no relationship between serum cholesterol and cholesterol content of the erythrocyte is apparent. This work, nonetheless, suggests that native polymorphisms which do affect membrane lipid composition would be expected to affect parasite entry. This supports investigation of erythrocyte biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms.
The effects of poverty reduction policy on health services utilization among the rural poor: a quasi-experimental study in central and western rural China
Authors: Zou Qi , He Xiaoqun , Li Zhong , Xu Wanchun , Zhang Liang
Published: November 2019

Background

China poverty reduction policy (PRP) addresses two important elements: the targeted poverty reduction (TPA) project since 2015 in line with social assistance policy as national policy; and reducing inequality in health services utilization by making provision of medical financial assistance (MFA). Therefore, this study aims to assess the effects of the PRP in health services utilization (both inpatient and outpatient services) among the central and western rural poor of China.

Methods

The study conducted household survey and applied propensity score matching (PSM) method to assess the effects of the PRP on health services utilization among the rural poor of Central and Western China. A sensitivity test was also performed on the PSM results to test their robustness.

Results

Key findings showed 17.6% of respondents were the beneficial of PRP. The average treatment effects on the treated (ATT) of the PRP on the inpatient visits within one year was found significantly positive (P = 0.026).

Conclusion

There has been relationship between PRP with medical financial assistance and reduction of inequality in health services utilization by the poorer, in particular to accessing the inpatient services from the county or township hospitals of China. Policy makers should pay attention for making provision of improving responsiveness of supply, when subsidizing on the demand side.
Analysis of key genes and their functions in placental tissue of patients with gestational diabetes mellitus
Authors: Wang Yuxia , Yu Haifeng , Liu Fangmei , Song Xiue
Published: November 2019

Background

This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM).

Methods

The GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA–transcription factor (TF)–DEG regulatory network was analyzed.

Results

In total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted.

Conclusions

Four candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.
Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers
Authors: Boynukalin Fazilet Kubra , Gultomruk Meral , Turgut Emre , Demir Berfu , Findikli Necati , Serdarogullari Munevver , Coban Onder , Yarkiner Zalihe , Bahceci Mustafa
Published: November 2019

Background

Endometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day.

Methods

This prospective cohort study includes patients who underwent single euploid FET. All patients received HRT with oestradiol valerate (EV) and 100 mg of intramuscular (IM) progesterone (P). FET was scheduled 117–120 h after the first IM administration of 100 mg P. The serum P level was analyzed 1 h before the embryo transfer (ET). In all cycles, only embryos that were biopsied on day 5 were utilized for FET. Next generation sequencing (NGS) was used for comprehensive chromosomal analysis.

Results

Overall, the ongoing pregnancy rate (OPR) was 58.9% (99/168). Data were then categorized according to the presence (Group I; n = 99) or the absence (Group II; n = 69) of an ongoing pregnancy. No significant differences regarding, female age, body mass index (BMI), number of previous miscarriages, number of previous live birth, sperm concentration, number of oocytes retrieved, number of mature oocytes (MII), rate of fertilized oocytes with two pronuclei (2PN), trophectoderm score, inner cell mass (ICM) score, endometrial thickness (mm), oestrodiol (E2) and P levels prior to IM P administration were found between two groups. The P levels on the day of ET (ng/ml) were significantly higher in Group I (28 (5.6–76.4) vs 16.4 (7.4–60) p = 0.039). The P level on the day of ET was a predictor of a higher OPR (p < 0.001 OR: 1.033 95%CI [1.009–1.056]) after multivariate analysis. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.716 (0.637–0.795). The optimal cut-off value for prediction of the OPR was a P level of 20.6 ng/ml (71.7% sensitivity, 56.5% specificity).

Conclusions

The present study suggests a minimum threshold of the serum P value on the day of ET that needs to be reached in HRT cycles to optimize the clinical outcome. Individualization of the P dosage should be evaluated in further studies.
Karyopherin α2-dependent import of E2F1 and TFDP1 maintains protumorigenic stathmin expression in liver cancer
Authors: Drucker Elisabeth , Holzer Kerstin , Pusch Stefan , Winkler Juliane , Calvisi Diego F. , Eiteneuer Eva , Herpel Esther , Goeppert Benjamin , Roessler Stephanie , Ori Alessandro , Schirmacher Peter , Breuhahn Kai , Singer Stephan
Published: November 2019

Background

Members of the karyopherin superfamily serve as nuclear transport receptors/adaptor proteins and provide exchange of macromolecules between the nucleo- and cytoplasm. Emerging evidence suggests a subset of karyopherins to be dysregulated in hepatocarcinogenesis including karyopherin-α2 (KPNA2). However, the functional and regulatory role of KPNA2 in liver cancer remains incompletely understood.

Methods

Quantitative proteomics (LC-MS/MS, ~ 1750 proteins in total) was used to study changes in global protein abundance upon siRNA-mediated KPNA2 knockdown in HCC cells. Functional and mechanistic analyses included colony formation and 2D migration assays, co-immunoprecipitation (CoIP), chromatin immunoprecipitation (ChIP), qRT-PCR, immmunblotting, and subcellular fractionation. In vitro results were correlated with data derived from a murine HCC model and HCC patient samples (3 cohorts, n > 600 in total).

Results

The proteomic approach revealed the pro-tumorigenic, microtubule (MT) interacting protein stathmin (STMN1) among the most downregulated proteins upon KPNA2 depletion in HCC cells. We further observed that KPNA2 knockdown leads to reduced tumor cell migration and colony formation of HCC cells, which could be phenocopied by direct knockdown of stathmin. As the underlying regulatory mechanism, we uncovered E2F1 and TFDP1 as transport substrates of KPNA2 being retained in the cytoplasm upon KPNA2 ablation, thereby resulting in reduced STMN1 expression. Finally, murine and human HCC data indicate significant correlations of STMN1 expression with E2F1/TFPD1 and with KPNA2 expression and their association with poor prognosis in HCC patients.

Conclusion

Our data suggest that KPNA2 regulates STMN1 by import of E2F1/TFDP1 and thereby provide a novel link between nuclear transport and MT-interacting proteins in HCC with functional and prognostic significance.
Built and social environmental factors influencing healthy behaviours in older Chinese immigrants to Australia: a qualitative study
Authors: Cerin Ester , Nathan Andrea , Choi Wing Ka , Ngan Winsfred , Yin Shiyuan , Thornton Lukar , Barnett Anthony
Published: November 2019

Background

Neighbourhood environments influence older adults’ health and health-enhancing behaviours, such as physical activity, eating a healthy diet and socialising. However, little is known about the effects of the neighbourhood environment on the health of older immigrants, the number of which is rapidly increasing in developed countries. Using Nominal Group Technique (NGT) sessions, this study of older Chinese immigrants to urban Melbourne, Australia, examined built and social environmental facilitators of and barriers to regular engagement in physical activity, eating a healthy diet and regular contact with other people.

Methods

Participants were recruited from four types of neighbourhoods stratified by walkability and proportion of Chinese dwellers. Twelve NGTs, four specific to each of physical activity, healthy diet and social contacts were conducted in Mandarin or Cantonese (91 participants). NGT responses from groups addressing the same questions were aggregated, similar items were combined, and scores combined across groups. Inductive thematic analysis was used to categorise answers into higher-order themes of factors associated with each behaviour.

Results

For physical activity, 29 facilitators and 28 barriers were generated with the highest ranked facilitator and barrier being “proximity to destinations” and “poor/inadequate public transport”, respectively. For healthy diet, 25 facilitators and 25 barriers were generated, the highest ranked facilitator and barrier were “high food safety standards/regulations” and “lack of family/household members’ social support for a healthy diet”. The social contacts NGTs generated 23 facilitators and 22 barriers, with the highest ranked facilitator and barrier being “proximity to destinations and activities” and “poor public transport”, respectively.

Discussion

Independent living arrangements and the accessibility of destinations of daily living (e.g., bilingual health services, libraries, places of worship and grocery stores / supermarkets), recreational facilities, affordable public transport, and community centres and activities for Chinese people are key elements for promoting regular engagement in physical activity, healthy eating and socialising in older Chinese immigrants. Governments should plan for the provision of this basic infrastructure of community facilities for older immigrants.
The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review
Authors: Bahsoun Soukaina , Coopman Karen , Akam Elizabeth C.
Published: November 2019

Mesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.
Ovarian function and reproductive outcome after ovarian tissue transplantation: a systematic review
Authors: Sheshpari Sepideh , Shahnazi Mahnaz , Mobarak Halimeh , Ahmadian Shahin , Bedate Alberto Miranda , Nariman-Saleh-Fam Ziba , Nouri Mohammad , Rahbarghazi Reza , Mahdipour Mahdi
Published: November 2019

The aim of this systematic review study is to summarize the current knowledge of ovarian tissue transplantation and provide insight on ovarian function, fertility and reproductive outcome following ovarian tissue transplantation. Relevant studies were identified by searching through PubMed, Cochrane Library, Embase, ProQuest, and Scopus databases until August 2018. Ovarian function by examination of the hormonal level was evaluated, together with follicular growth, the return of menstrual cycle and assessment of reproductive consequences: pregnancy, miscarriage rates and live birth after transplantation. Studies including female patients aged between 22 and 49 years that were subjected to ovarian tissue transplantation were considered. A total of 1185 studies were identified in the primary search. Titles and abstracts were screened for assessment of the inclusion criteria. Finally, twenty-five articles met the criteria and were included in this study. In general, 70% of patients that underwent ovarian tissue transplantation had ovarian and endocrine function restoration as well as follicular growth. Pregnancy was reported with 52% of the patients. The available evidence suggests that ovarian tissue transplantation is a useful and an applied approach to restore hormonal function, endocrine balance and eventually fertility outcomes in patients that are predisposed to lose their fertility, diagnosed with premature ovarian failure (POF), as well as women undergoing cancer treatments. Identification of the techniques with the lowest invasions for follicular and oocyte development after ovarian tissue transplantation aiming to reduce probable adverse effects after treatment is indispensable.