bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between symptom burden and systemic inflammation differs between male and female athletes following concussion
Authors: Di Battista Alex P. , Churchill Nathan , Rhind Shawn G. , Richards Doug , Hutchison Michael G.
Published: March 2020

Background

Inflammation appears to be an important component of concussion pathophysiology. However, its relationship to symptom burden is unclear. Therefore, the purpose of this study was to evaluate the relationship between symptoms and inflammatory biomarkers measured in the blood of male and female athletes following a sport-related concussion (SRC).

Results

Forty athletes (n = 20 male, n = 20 female) from nine interuniversity sport teams at a single institution provided blood samples within one week of an SRC. Twenty inflammatory biomarkers were quantitated by immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms. Partial least squares (PLS) analyses were used to evaluate the relationship(s) between biomarkers and symptoms. In males, a positive correlation between interferon (IFN)-γ and symptom severity was observed following SRC. The relationship between IFN-γ and symptoms was significant among all symptom clusters, with cognitive symptoms displaying the largest effect. In females, a significant negative relationship was observed between symptom severity and cytokines IFN-γ, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO); a positive relationship was observed between symptom severity and MCP-4. Inflammatory mediators were significantly associated with all symptom clusters in females; the somatic symptom cluster displayed the largest effect.

Conclusion

These results provide supportive evidence of a divergent relationship between inflammation and symptom burden in male and female athletes following SRC. Future investigations should be cognizant of the potentially sex-specific pathophysiology underlying symptom presentation.
The low-copy nuclear gene Agt1 as a novel DNA barcoding marker for Bromeliaceae
Authors: Bratzel Fabian , Heller Sascha , Cyrannek Nadine , Paule Juraj , Leme Elton M. C. , Loreth Anna , Nowotny Annika , Kiefer Markus , Till Walter , Barfuss Michael H. J. , Lexer Christian , Koch Marcus A. , Zizka Georg
Published: March 2020

Background

The angiosperm family Bromeliaceae comprises over 3.500 species characterized by exceptionally high morphological and ecological diversity, but a very low genetic variation. In many genera, plants are vegetatively very similar which makes determination of non flowering bromeliads difficult. This is particularly problematic with living collections where plants are often cultivated over decades without flowering. DNA barcoding is therefore a very promising approach to provide reliable and convenient assistance in species determination. However, the observed low genetic variation of canonical barcoding markers in bromeliads causes problems.

Result

In this study the low-copy nuclear gene Agt1 is identified as a novel DNA barcoding marker suitable for molecular identification of closely related bromeliad species. Combining a comparatively slowly evolving exon sequence with an adjacent, genetically highly variable intron, correctly matching MegaBLAST based species identification rate was found to be approximately double the highest rate yet reported for bromeliads using other barcode markers.

Conclusion

In the present work, we characterize Agt1 as a novel plant DNA barcoding marker to be used for barcoding of bromeliads, a plant group with low genetic variation. Moreover, we provide a comprehensive marker sequence dataset for further use in the bromeliad research community.
Safety and outcome of gastrostomy tube placement in patients with Loeys-Dietz syndrome
Authors: Frischmeyer-Guerrerio Pamela A. , MacCarrick Gretchen , Dietz Harry C. , Stewart F. Dylan , Guerrerio Anthony L.
Published: March 2020

Background

Loeys-Dietz syndrome (LDS) is a systemic connective tissue disease (CTD) associated with a predisposition for intestinal inflammation, food allergy, and failure to thrive, often necessitating nutritional supplementation via gastrostomy tube. Poor wound healing has also been observed in in some patients with CTD, potentially increasing the risk of surgical interventions. We undertook to determine the safety and efficacy of gastrostomy tube placement in this population.

Methods

We performed a retrospective cohort study of 10 LDS patients who had a total of 12 gastrostomy tubes placed.

Results

No procedural complications occurred, although one patient developed buried bumper syndrome in the near post-procedural time period and one patient had a small abscess at a surgical stitch. Most patients exhibited improvements in growth, with a median immediate improvement in BMI Z-score of 0.2 per month following the institution of gastrostomy tube feedings. Those with uncontrolled inflammation due to inflammatory bowel disease or eosinophilic gastrointestinal disease showed the least benefit and in some cases failed to demonstrate significant weight gain despite nutritional supplementation.

Conclusions

Gastrostomy tube placement (surgical or endoscopic) is a generally safe and a reasonable therapeutic option for patients with LDS despite their underlying CTD.
Informal caregivers’ views on the quality of healthcare services provided to older patients aged 80 or more in the hospital and 30 days after discharge
Authors: Lilleheie Ingvild , Debesay Jonas , Bye Asta , Bergland Astrid
Published: March 2020

Background

In the European Union (EU), informal caregivers provide 60% of all care. Informal caregiving ranges from assistance with daily activities and provision of direct care to helping care recipients to navigate within complex healthcare and social services systems. While recent caregiver surveys document the impact of informal caregivers, systematic reviews show that they have unmet needs.

Because of the political desire to reduce the length of hospital stays, older patients are discharged from the hospital ‘quicker and sicker’ than before. The transition between different levels of the healthcare system and the period after hospital discharge is critical for elderly patients.

Caregivers’ perspectives on the quality of older patients’ care journeys between levels of the healthcare system may provide valuable information for healthcare providers and policymakers. This study aims to explore older patient’s informal caregivers’ views on healthcare quality in the hospital and in the first 30 days after hospitalisation.

Method

We conducted semi-structured individual interviews with 12 participants to explore and describe informal caregivers’ subjective experiences of providing care to older relatives. The interviews were then transcribed and analysed thematically.

Results

The analysis yielded the overarching theme ‘Informal caregivers – a health service alliance – quality contributor’, which was divided into four main themes: ‘Fast in, fast out’, ‘Scant information’, ‘Disclaimer of responsibility’ and ‘A struggle to secure professional care’. The healthcare system seemed to pay little attention to ensuring mutual understandings between those involved in discharge, treatment and coordination. The participants experienced that the healthcare providers’ main focus was on the patients’ diseases, although the health services are supposed to view patients holistically.

Conclusion

Based on the information given by informal caregivers, health services must take into account each person’s needs and preferences. To deliver quality healthcare, better coordination between inter-professional care teams and the persons they serve is necessary. Health professionals must strengthen the involvement of caregivers in transitions between care and healthcare. Future work should evaluate targeted strategies for formal caregivers to cooperate, support and empower family members as informal caregivers.
Study protocol of a quasi-experimental trial to compare two models of home care for older people in the primary setting
Authors: Burgos-Díez Carolina , Sequera-Requero Rosa Maria , Tarazona-Santabalbina Francisco José , Contel-Segura Joan Carles , Monzó-Planella Marià , Santaeugènia-González Sebastià Josep
Published: March 2020

Background

Preventive home visits are suited for patients with reduced mobility, such as older people. Healthcare needs for older patients are expected to increase due to the extended life expectancy estimated in coming years. The implementation of low-cost, patient-centered methodologies may buffer this rise in health care costs without affecting the quality of service. In order to find the best home care model with less investment, this paper describes a study protocol comparing two models of home care for older people.

Methods

We describe a quasi-experimental study that compares the outcome of two different home care models already implemented in two primary care centers in Badalona (Barcelona, Spain). The traditional model (control model) is integrated in the sense that is continuous, the same primary care center team looks after its assigned patients both at the center and in preventive home visits. The new functional home care model (study model), consisting of a highly trained team, is specifically designed to meet patient needs and give total attention to preventive home interventions. The study will start and end on the expected dates, June 2018 to October 2020, and include all patients over 65 years old already enrolled in the home care programs of the primary care centers selected. The primary endpoint assessed will be the difference in hospitalization days between patients included in both home care programs. Other variables regarding health status, quality of care and resource utilization will also be compared between the two models.

Discussion

The study in progress will assess whether a functional and highly trained home care team will meet the ever-aging population needs in terms of cost and health outcomes better than a traditional, integrated one. Lessons learned from this pilot study will provide guidelines for a future model of home care based on the IHI Triple Aim: better care, better health, and lower costs.

Trial registration

Registered in ClinicalTrials.gov (Identifier: NCT03461315; March 12, 2018).
Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective review
Authors: Lai Jana , Nguyen Cattram , Tabwaia Beia , Nikuata Agnes , Baueri Nikarawa , Timeon Eretii , Diaaldeen Mohammed , Iuta Tinai , Ozturk Murat Hakan , Moore Aaron , Hall Alice , Nyambat Batmunkh , Davis Stephanie , Rahman Ataur , Erasmus Wendy , Fox Kimberley , Russell Fiona
Published: March 2020

Background

Kiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken.

Methods

Inpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010–December 2013 (pre-rotavirus vaccine) and January 2016–September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction.

Results

The incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12·8% vs. 7·2%, p < 0·001) and all-cause under-five mortality (15·9% vs. 5·7%, p = 0·006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction.

Conclusions

AGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.
Factors associated with sepsis development in 606 Spanish adult patients with cellulitis
Authors: Collazos J. , de la Fuente B. , de la Fuente J. , García A. , Gómez H. , Menéndez C. , Enríquez H. , Sánchez P. , Alonso M. , López-Cruz I. , Martín-Regidor M. , Martínez-Alonso A. , Guerra J. , Artero A. , Blanes M. , Asensi V.
Published: March 2020

Background

Cellulitis, a frequent cause of admission of adult patients to medical wards, occasionally evolves to sepsis. In this study we analyze the factors related to sepsis development.

Methods

Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Sepsis was diagnosed according to the criteria of the 2016 International Sepsis Definitions Conference. Multiple logistic regression modelling was performed to determine the variables independently associated with sepsis development.

Results

Mean age was 63.4 years and 51.8% were men. Overall 65 (10.7%) patients developed sepsis, 7 (10.8%) of whom died, but only 4 (6.2%) due to cellulitis. Drawing of blood (P < 0.0001) or any (P < 0.0001) culture, and identification of the agent (P = 0.005) were more likely among patients with sepsis. These patients had also a longer duration of symptoms (P = 0.04), higher temperature (P = 0.03), more extensive cellulitis (P = 0.02), higher leukocyte (P < 0.0001) and neutrophil (P < 0.0001) counts, serum creatinine (P = 0.001), and CRP (P = 0.008) than patients without sepsis. Regarding therapy, patients with sepsis were more likely to undergo changes in the initial antimicrobial regimen (P < 0.0001), received more antimicrobials (P < 0.0001), received longer intravenous treatment (P = 0.03), and underwent surgery more commonly (P = 0.01) than patients without sepsis. Leukocyte counts (P = 0.002), serum creatinine (P = 0.003), drawing of blood cultures (P = 0.004), change of the initial antimicrobial regimen (P = 0.007) and length of cellulitis (P = 0.009) were independently associated with sepsis development in the multivariate analysis.

Conclusions

Increased blood leukocytes and serum creatinine, blood culture drawn, modification of the initial antimicrobial regimen, and maximum length of cellulitis were associated with sepsis in these patients.
Long-term immunological responses to treatment among HIV-2 patients in Côte d’Ivoire
Authors: Minchella Peter A. , Adjé-Touré Christiane , Zhang Guoqing , Tehe Andre , Hedje Judith , Rottinghaus Erin R. , Kohemun Natacha , Aka Micheline , Diallo Karidia , Ouedraogo G. Laissa , De Cock Kevin M. , Nkengasong John N
Published: March 2020

Background

Studies indicate that responses to HIV-2 treatment regimens are worse than responses to HIV-1 regimens during the first 12 months of treatment, but longer-term treatment responses are poorly described. We utilized data from Côte d’Ivoire’s RETRO-CI laboratory to examine long-term responses to HIV-2 treatment.

Methods

Adult (≥15 years) patients with baseline CD4 counts < 500 cells/μl that initiated treatment at one of two HIV treatment centers in Abidjan, Côte d’Ivoire between 1998 and 2004 were included in this retrospective cohort study. Patients were stratified by baseline CD4 counts and survival analyses were employed to examine the relationship between HIV type and time to achieving CD4 ≥ 500 cells/μl during follow up.

Results

Among 3487 patients, median follow-up time was 4 years and 57% had documented ART regimens for > 75% of their recorded visits. Kaplan-Meier estimates for achievement of CD4 ≥ 500 cells/μl after 6 years of follow-up for patients in the lower CD4 strata (< 200 cells/μl) were 40% (HIV-1), 31% (HIV-dual), and 17% (HIV-2) (log-rankp < 0.001). Cox Regression indicated that HIV-1 was significantly associated with achievement of CD4 ≥ 500 cells/μl during follow-up, compared to HIV-2.

Conclusions

Sub-optimal responses to long-term HIV-2 treatment underscore the need for more research into improved and/or new treatment options for patients with HIV-2. In many West African countries, effective treatment of both HIV-1 and HIV-2 will be essential in the effort to reach epidemic control.
Prevalence estimates of human immunodeficiency virus (HIV) infection among visceral leishmaniasis infected people in Northwest Ethiopia: a systematic review and meta-analysis
Authors: Mohebali Mehdi , Yimam Yonas
Published: March 2020

Background

In Ethiopia, by the end of 2018, an estimated 690,000 people are infected with HIV and the annual cases of Visceral Leishmaniasis (VL) is estimated to be between 4000 and 5000 with over 3.2 million people are at risk. Northwest Ethiopia accounts for over 60% cases of VL in the country. Prevalence of HIV infection among VL infected people in Ethiopia has not yet been synthesized. Therefore, we aimed to estimate the pooled prevalence of HIV infection among VL infected people in Northwest Ethiopia with the hope that it would guide the development of a more robust and cost-effective intervention strategies.

Methods

In this systematic review and meta-analysis, we searched six international databases: PubMed, Ovid MEDLINE®, Embase, Scopus, Google Scholar, and ProQuest Dissertations & Theses. We also searched reference lists of included studies and Ethiopian universities electronic thesis and dissertation repositories. The search was performed until June 30,2019. Funnel plot symmetry visualization confirmed by Egger’s regression asymmetry test and Begg rank correlation methods was used to assess publication bias. Pooled prevalence estimate was calculated using Der Simonian and Laird’s random Effects model. We went further to perform univariate meta-regression and subgroup analysis to identify a possible sources of heterogeneity among the studies. STATA software (version 14, Texas, USA) was used for analysis.

Results

From 1286 citations identified by our search, 19 relevant studies with 5355 VL infected individuals were included in this meta-analysis. The pooled prevalence of HIV infection among VL infected individuals in Northwest Ethiopia was 24% (95%CI: 17–30%). The result of sensitivity analysis demonstrated that the pooled prevalence estimate was robust and not one-study dependent. The pooled prevalence estimate of HIV infection among VL infected people in Northwest Ethiopia ranged from 20.88% (95%CI: 15.91–25.86) to 24.86% (95%CI: 18.57–31.14) after a single study was deleted.

Conclusions

The burden of HIV infection in people infected with VL in Northwest Ethiopia is considerably high. Integrating HIV/AIDS surveillance among VL infected people would improve case detection as well as prevention and control of disease spread.
Case report: Mycobacterium monacense isolated from the blood culture of a patient with pulmonary infection
Authors: Yuan Chenyan , Lu Huixia , Yang Congshan , Gao Wei , Wang Hailiang , Wu Guoqiu
Published: March 2020

Background

The poorly known mycobacterial speciesMycobacterium monacenseis a rapidly growing non-tuberculous mycobacterium that was first described in 2006 (Reischl et al., Int J Syst Evol Microbiol 56:2575-8, 2006); it has been reported that its isolation is usually associated with skin and lung infections, especially in immunosuppressed patients (Hogardt et al., Jpn J Infect Dis 61:77-8, 2008; Taieb et al., J Hand Surg Am 33:94-6, 2008; Therese et al., Lung India 28:124-6, 2011; Shojaei et al., Ann Lab Med 32:87-90, 2012; Romero et al., New Microbes New Infect 10:112-5, 2016 ). The clinical significance ofMycobacterium monacenseis not yet fully understood. Here, we report the first isolation ofMycobacterium monacensefrom the blood culture of a patient in China with severe pneumonia.

Case presentation

On June 26, 2018, a 38-year-old man was admitted to the intensive care unit with breathing difficulty. One day prior, he was discovered with his face immersed in a small pond (non-chlorinated water) and with limb convulsions. He had undergone craniocerebral surgery after trauma 5 years earlier, which left him with epilepsy as a sequela. Bilateral diffuse ground-glass opacity was found in the lungs on chest X ray and chest CT image at admission. The result of the HIV serology test of the patient was negative. The patient was diagnosed with severe pneumonia. Drug-susceptibleKlebsiella pneumoniaeandCandida glabratawere isolated in the BALF, and yellow-pigmented colonies were isolated from blood cultures of the patient. The strain isolated from blood was identified by 16S rDNA sequencing asMycobacteria monacense, which is a rapidly growing mycobacterium (RGM). The patient was treated with a combination of cefoperazone sulbactam, linezolid and voriconazole for 10 days, and the symptoms improved. During the one-year follow-up time, the patient did not relapse.

Conclusions

We report the first case ofM. monacenseisolated from blood cultures in a patient with severe pneumonia, which provided evidence that the environmental microorganism possessed pathogenic characteristics.
Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations
Authors: Athota Jeevana Praharsha , Bhat Meenakshi , Nampoothiri Sheela , Gowrishankar Kalpana , Narayanachar Sanjeeva Ghanti , Puttamallesh Vinuth , Farooque Mohammed Oomer , Shetty Swathi
Published: March 2020

Background

Noonan syndrome (NS), an autosomal dominant developmental genetic disorder, is caused by germline mutations in genes associated with the RAS / mitogen-activated protein kinase (MAPK) pathway. In several studiesPTPN11is one of the genes with a significant number of pathogenic variants in NS-affected patients. Therefore, clinically diagnosed NS individuals are initially tested for pathogenic variants inPTPN11gene to confirm the relationship before studying genotype–phenotype correlation.

Methods

Individuals (363) with clinically diagnosed NS from four hospitals in South India were recruited and the exons ofPTPN11gene were sequenced.

Results

Thirty-two previously described pathogenic variants in eight different exons inPTPN11gene were detected in 107 patients, of whom 10 were familial cases. Exons 3, 8 and 13 had the highest number of pathogenic variants. The most commonly identified pathogenic variants in this series were in exon 8 (c.922A > G, c.923A > G), observed in 22 of the affected. Congenital cardiac anomalies were present in 84% of the mutation-positive cohort, the majority being defects in the right side of the heart. The most common facial features were downward-slanting palpebral fissures, hypertelorism and low-set posteriorly rotated ears. Other clinical features included short stature (40%), pectus excavatum (54%) and, in males, unilateral or bilateral cryptorchidism (44%).

Conclusion

The clinical features and mutational spectrum observed in our cohort are similar to those reported in other large studies done worldwide. This is the largest case series of NS-affected individuals withPTPN11mutations described till date from India.
Barriers and enablers to detection and management of chronic kidney disease in primary healthcare: a systematic review
Authors: Neale Elizabeth P. , Middleton Justin , Lambert Kelly
Published: March 2020

Background

Chronic kidney disease (CKD) is growing population health concern worldwide, and with early identification and effective management, kidney disease progression can be slowed or prevented. Most patients with risk factors for chronic kidney disease are treated within primary healthcare. Therefore, it is important to understand how best to support primary care providers (PC-P) to detect and manage chronic kidney disease. The aim of this systematic review was to evaluate barriers and enablers to the diagnosis and management of CKD in primary care.

Methods

A systematic review of qualitative research on the barriers and/or enablers to detection and/or management of CKD in adults within primary healthcare was conducted. The databases Medline (EBSCO), PubMed, Cochrane CENTRAL, CINAHL (EBSCO) and Joanna Briggs Institute Evidence Based Practice (Ovid) were searched until 27th August 2019. Barriers and/or enablers reported in each study were identified, classified into themes, and categorised according to the Theoretical Domains Framework.

Results

A total of 20 studies were included in this review. The most commonly reported barriers related to detection and management of CKD in primary care were categorised into the ‘Environmental context and resources’ domain (n = 16 studies). Overall, the most common barrier identified was a lack of time (n = 13 studies), followed by a fear of delivering a diagnosis of CKD, and dissatisfaction with CKD guidelines (both n = 10 studies). Overall, the most common enabler identified was the presence of supportive technology to identify and manage CKD (n = 7 studies), followed by the presence of a collaborative relationship between members of the healthcare team (n = 5 studies).

Conclusion

This systematic review identified a number of barriers and enablers which PC-P face when identifying and managing CKD. The findings of this review suggest a need for time-efficient strategies that promote collaboration between members of the healthcare team, and practice guidelines which consider the frequently co-morbid nature of CKD. Enhanced collaboration between PC-P and nephrology services may also support PC-Ps when diagnosing CKD in primary care, and facilitate improved patient self-management.
Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington’s disease
Authors: Ratna Nikhil , Kamble Nitish L. , Venkatesh Sowmya D. , Purushottam Meera , Pal Pramod K. , Jain Sanjeev
Published: March 2020

Background

Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India.

Methods

We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring.

Results

Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n = 81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p < 0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up.

Conclusions

This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.
Maternal plasma lipid levels across pregnancy and the risks of small-for-gestational age and low birth weight: a cohort study from rural Gambia
Authors: Okala Sandra G. , Sise Ebrima A. , Sosseh Fatou , Prentice Andrew M. , Woollett Laura A. , Moore Sophie E.
Published: March 2020

Background

Sub-optimal maternal lipid levels during pregnancy may be implicated in the pathophysiological mechanisms leading to low birth weight (LBW) and small-for-gestational-age (SGA). We aimed to determine whether maternal lipid levels across pregnancy were associated with birth weight and the risks of LBW and SGA in rural Gambia.

Methods

This secondary analysis of the ENID trial involved 573 pregnant women with term deliveries. Plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were analyzed at enrolment (mean (SD) = 13.9 (3.3) weeks gestation), 20 and 30 weeks gestation as continuous variables and percentile groups. Regression models with adjustment for confounders were used to examine associations between gestational lipid levels and birth weight and the risks of LBW (birth weight < 2500 g) and SGA (<10th percentile INTERGROWTH-21ST for birth weight).

Results

There were 7.9% LBW and 32.5% SGA infants. At enrolment, every unit increase in HDL-c was associated with a 2.7% (P = 0.011) reduction in relative risk of LBW. At 20 weeks gestation, every unit increase in TC levels was associated with a 1.3% reduction in relative risk of LBW (P = 0.002). Low (<10th percentile) HDL-c at enrolment or at 20 weeks gestation was associated with a 2.6 (P = 0.007) and 3.0 (P = 0.003) times greater risk of LBW, respectively, compared with referent (10th─90th) HDL-c. High (>90th percentile) LDL-c at 30 weeks gestation was associated with a 55% lower risk of SGA compared with referent LDL-c (P = 0.017). Increased levels of TC (β = 1.3,P = 0.027) at 20 weeks gestation and of TC (β = 1.2,P = 0.006) and LDL-c (β = 1.5,P = 0.002) at 30 weeks gestation were all associated with higher birth weight.

Conclusions

In rural Gambia, lipid levels during pregnancy were associated with infant birth weight and the risks of LBW and SGA. Associations varied by lipid class and changed across pregnancy, indicating an adaptive process by which maternal lipids may influence fetal growth and birth outcomes.

Trial registration

This trial was registered asISRCTN49285450on: 12/11/2009.
Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series
Authors: Tamura Ryota , Morimoto Yukina , Kosugi Kenzo , Sato Mizuto , Oishi Yumiko , Ueda Ryo , Kikuchi Ryogo , Nagashima Hideaki , Hikichi Tetsuro , Noji Shinobu , Kawakami Yutaka , Sasaki Hikaru , Yoshida Kazunari , Toda Masahiro
Published: March 2020

Background

The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated.

Methods

We performed the first clinical trial to assess VEGFR1 and 2 vaccination along with temozolomide (TMZ) -based chemoradiotherapy for the patients with primary glioblastomas. Furthermore, histopathological changes after the vaccination were evaluated using paired pre- and post- vaccination specimens.

Results

The disappearance of radiographically enhanced lesion was observed in 2 patients after the vaccination, including one in which the methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not observed. The histopathological findings of pre- and post-vaccination specimens demonstrated that tumor vessels showed negative or slight VEGFRs expressions after the vaccination and most endothelial cells were covered with PDGFR-β-positive pericytes. Notably, CTLs induced by VEGFRs peptide vaccination attacked not only tumor vessels but also tumor cells and regulatory T cells expressing VEGFRs even in recurrent tumors.

Conclusions

VEGFR1 and 2 vaccination may have a preliminary synergistic effect when administered with TMZ. The limitation of the present study was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study.

Trial registration

This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.
A phase II open label, randomised study of ipilimumab with temozolomide versus temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: the Ipi-Glio trial protocol
Authors: Brown Nicholas F. , Ng Stasya M. , Brooks Claire , Coutts Tim , Holmes Jane , Roberts Corran , Elhussein Leena , Hoskin Peter , Maughan Tim , Blagden Sarah , Mulholland Paul
Published: March 2020

Background

Median survival for patients with glioblastoma is less than a year. Standard treatment consists of surgical debulking if feasible followed by temozolomide chemo-radiotherapy. The immune checkpoint inhibitor ipilimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and has shown clinical efficacy in preclinical models of glioblastoma. The aim of this study is to explore the addition of ipilimumab to standard therapy in patients with glioblastoma.

Methods/design

Ipi-Glio is a phase II, open label, randomised study of ipilimumab with temozolomide (Arm A) versus temozolomide alone (Arm B) after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma. Planned accrual is 120 patients (Arm A: 80, Arm B: 40). Endpoints include overall survival, 18-month survival, 5-year survival, and adverse events. The trial is currently recruiting in seven centres in the United Kingdom.

Trial registration

ISRCTN84434175. Registered 12 November 2018.
Lipid profile and risk of ovarian tumours: a meta-analysis
Authors: Onwuka Justina Ucheojor , Okekunle Akinkunmi Paul , Olutola Olaniyi Matthew , Akpa Onoja Matthew , Feng Rennan
Published: March 2020

Background

Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT.

Methods

Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed usingI2statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias.

Results

Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis andI2statistics ranged between 97 and 99%. Mean circulating TC (− 16.60 [− 32.43, − 0.77]mg/dL;P = 0.04) and HDL (− 0.25[− 0.43, − 0.08]mmol/L;P = 0.005) were significantly lower among OT cases compared to non-OT cases.

Conclusion

Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.
Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and prognostic nutritional index for predicting clinical outcomes in T1–2 rectal cancer
Authors: Xia Li-jian , Li Wen , Zhai Jian-cheng , Yan Chuan-wang , Chen Jing-bo , Yang Hui
Published: March 2020

Background

Inflammation-related parameters have been revealed to have prognostic value in multiple caners. However, the significance of some inflammation-related parameters, including the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and prognostic nutritional index (PNI), remains controversial in T1–2 rectal cancer (RC).

Methods

Clinical data of 154 T1–2 RC patients were retrospectively reviewed. The cut-off values for NLR, PLR, LMR, and PNI were determined by receiver operating characteristic curves. The relationships of these parameters with postoperative morbidities and prognosis were statistically analysed.

Results

The optimal cut-off values for preoperative NLR, PLR, LMR and PNI were 2.8, 140.0, 3.9, and 47.1, respectively. Significant but heterogeneous associations were found between NLR, PLR, LMR and PNI and clinicopathological factors. In addition, high NLR, high PLR, and low PNI were correlated with an increased postoperative morbidity rate. Patients with high NLR/PLR or low LMR/PNI had lower OS and DFS rates. On multivariate analysis, only high NLR was identified as an independent risk factor for poor DFS.

Conclusions

NLR, PLR, and PNI are valuable factors for predicting postoperative complications in T1–2 RC patients. A preoperative NLR of more than 2.8 is an independent prognostic factor for poor DFS in T1–2 RC patients.
Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin
Published: March 2020

Background

Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC.

Methods

Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).

Results

USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK).

Conclusion

USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.
Age- and gender-specific trends in respiratory outpatient visits and diagnoses at a tertiary pediatric hospital in China: a 10-year retrospective study
Authors: Shi Peng , Zhang Xiaobo , Liu Lijuan , Tang Liangfeng , Li Jing , Wang Libo , Li Albert M. , Cao Yang , Xu Hong , Huang Guoying
Published: March 2020

Background

Respiratory infections are one of three leading causes of childhood mortality, and worldwide increase and recent plateau in childhood asthma has been reported. However, data on trends of respiratory diseases over long period of time is limited. This study aimed to determine the trends of respiratory disease outpatient visits (ROVs) and diagnoses (RODs) in one of the largest children’s teaching hospitals in China between 2009 and 2018.

Methods

A retrospective study based on routine administrative data was designed and implemented according to the RECORD statement. Demographic details and diagnoses of the outpatients < 18 years visiting the respiratory department of the hospital were extracted from the Hospital Information System. Age- and gender-specific trends were illustrated by calculating average annual growth rate (AAGR) for ROVs and comparing change of proportion for different RODs over time.

Results

There were 698,054 ROVs from 285,574 children (40.4% female). AAGR of ROVs was 15.2%. Children aged 4 to < 7 years had a faster increase than other age groups. Bronchitis (27.6%), pneumonia (18.5%), pneumonia affecting other systems (18.4%), asthma and status asthmaticus (10.7%), and vasomotor and allergic rhinitis (9.2%) accounted for 84.4% of all RODs. The proportion of bronchitis decreased across years, with the concomitant increasing trend in the proportion of pneumonia. Age-specific trend in diagnoses showed greater proportion of asthma in all visits for the children aged 7 to < 18 years than younger children. Gender-specific trend in diagnoses showed the proportion of asthma was greater for males but the AAGR was greater for females.

Conclusion

The persistent upward trend in ROVs was observed among children at different ages and a gender difference was also seen. In contrast to what has been reported, burden of asthma and allergies diseases continues to increase locally.
Physical activity and creativity of children and youths
Authors: Piya-amornphan Nitita , Santiworakul Anoma , Cetthakrikul Salila , Srirug Phatcharawadee
Published: March 2020

Background

Childhood is an important period for developing maturity in thinking. Accumulating evidence shows the association between physical activity and cognitive function. Although both the intelligence quotient and emotional quotient have been reported to be associated with physical activity, there is a limited amount of published research regarding the association between physical activity and cognitive function in children and youths. With respect to creativity, an important skill for the twenty-first century, little evidence on the creative quotient promotion in childhood is available. The present study, therefore, is designed to explore the correlation between physical activity and creativity.

Methods

The participants included 1447 students with different age groups in 34 schools from Southern Thailand. Age groups were categorized according to Thailand’s 2016 Report Card on Physical Activity for Children and Youth, where 521 students were aged 6–9 years, 487 students were aged 10–13 years, and 439 students were aged 14–17 years. Creativity was measured through the use of the Test for Creative Thinking-Drawing Production (TCT-DP). Active play, time with family and peers, and sedentary behavior were monitored by the Thailand Physical Activity Children Survey-the Student Questionnaire (TPACS-SQ).

Results

The correlation between the TCT-DP score representing creativity and active play was noticed in adolescents (r = 0.148, p = 0.001), but not found in participants aged 6–13 years. Active play was associated with time with family and peers in all age groups (r = 0.485, p <  0.001).

Conclusions

The present data supports the idea that optimal physical activity is required during childhood for developing thinking process. Promotion of active play with family and peers may facilitate creativity skills.
Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review
Authors: Niceta Marcello , Dentici Maria Lisa , Ciolfi Andrea , Marini Romana , Barresi Sabina , Lepri Francesca Romana , Novelli Antonio , Bertini Enrico , Cappa Marco , Digilio Maria Cristina , Dallapiccola Bruno , Tartaglia Marco
Published: March 2020

Background

Joubert syndrome is a recessive neurodevelopmental disorder characterized by clinical and genetic heterogeneity. Clinical hallmarks include hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern cognitive impairment and, the molar tooth sign is the pathognomonic midbrain-hindbrain malformation on magnetic resonance imaging. The disorder is predominantly caused by biallelic mutations in more than 30 genes encoding proteins with a pivotal role in morphology and function of the primary cilium. Oligogenic inheritance or occurrence of genetic modifiers has been suggested to contribute to the variability of the clinical phenotype. We report on a family with peculiar clinical spectrum Joubert syndrome molecularly and clinically dissecting a complex phenotype, in which hypogonadism, pituitary malformation and growth hormone deficiency occur as major features.

Case presentation

A 7 year-old male was enrolled in a dedicated “Undiagnosed Patients Program” for a peculiar form of Joubert syndrome complicated by iris and retinochoroidal coloboma, hypogonadism pituitary malformation, and growth hormone deficiency. The molecular basis of the complex phenotype was investigated by whole exome sequencing. The concomitant occurrence of homozygosity for mutations in KIF7 and KIAA0556 was identified, and the assessment of major clinical features associated with mutations in these two genes provided evidence that these two independent events represent the cause underlying the complexity of the present clinical phenotype.

Conclusion

Beside the clinical variability of Joubert syndrome, co-occurrence of mutations in ciliopathy-associated genes may contribute to increase the clinical complexity of the trait.
Service user and family participation in mental health policy making in Timor-Leste: a qualitative study with multiple stakeholders
Authors: Hall Teresa , Kakuma Ritsuko , Palmer Lisa , Minas Harry , Martins João , Armstrong Greg
Published: March 2020

Background

Participation in mental health system strengthening by people with mental health problems and their families is a cornerstone of people-centred mental health care, yet there is a dearth of research about participation from low- and middle-income countries (LMICs), particularly from the Asia Pacific region. Hence, this study aimed to assess the current situation, challenges, enabling factors and future actions for service user and family participation in mental health policy making in Timor-Leste.

Methods

In-depth interviews were conducted with 85 adults (≥18 years) who were: (1) mental health service users (n = 20) and their families (n = 10); (2) government decision makers (n = 10); (3) mental health and social service providers (n = 23); (4) civil society (n = 9); and (5) other groups (n = 13). Interview data was analysed using framework analysis.

Results

There was limited service user, family and community participation in mental health policy making in Timor-Leste. Perceptions that policy making is a technical exercise and that people with mental health problems lack cognitive capacity, and a lack of supportive mechanisms challenged participation. Enabling factors were a strong focus on human rights within the social sector, and existing mechanisms for advocacy and representation of people with disabilities in social policy making. Participants suggested bolstering civil society representation of people with mental health problems, and increasing mental health awareness and literacy, including government competencies to facilitate service user participation.

Conclusion

The findings highlight the need for theoretical and practical focus on the role of family within mental health system development in LMICs. Global mental health research and practice should adopt a critical approach to mental health service user and family participation to ensure that the concept and strategies to achieve this are embedded in LMIC knowledge.