bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of overweight with postoperative acute kidney injury among patients receiving orthotopic liver transplantation: an observational cohort study
Authors: Zhou Jian , Lyu Lin , Zhu Lin , Liang Yongxin , Dong He , Chu Haichen
Published: June 2020

Background

Acute kidney injury (AKI) is a common postoperative complication of orthotopic liver transplantation (OLT). So far, little attention has been paid on the association between overweight and AKI after OLT, and animal models or clinical studies have drawn conflicting conclusions. The objective of our study was to determine whether overweight (BMI [Body Mass Index] ≥ 25 kg/m2) is associated with an increased risk of AKI after OLT.

Methods

This retrospective cohort study included 244 patients receiving OLT in the Affiliated Hospital of Qingdao University between January 1, 2017, and August 29, 2019. Preoperative, intraoperative, and postoperative data were collected retrospectively. The primary outcome was the development of AKI as defined by Kidney Disease, Improving Global Outcome (KIDGO) staging system. Logistic regression analysis was used to determine the relationship between overweight and the occurrence of postoperative AKI. Data analysis was conducted from September to October 2019, revision in April 2020.

Results

Among 244 patients receiving OLT (mean [standard deviation] age, 54.1 [9.6] years; 84.0% male) identified, 163 patients (66.8%) developed postoperative AKI. Overweight (BMI ≥ 25 kg/m2) was associated with a higher rate of postoperative severe AKI (stage 2/3) compared with normal weight (18.5 ≤ BMI < 25 kg/m2) (41 [47.7%] vs 39 [28.7%]; adjusted odds ratio [OR], 2.539; 95% confidence interval [CI], 1.389–4.642; P = 0.002). Furthermore, patients with obese were at even higher risk of postoperative severe AKI after controlling for confounding factors (adjusted OR: 3.705; 95% CI: 1.108–12.388; P = 0.033).

Conclusions

Overweight is independently associated with an increased risk of postoperative severe AKI among patients receiving OLT. The association of BMI with severe AKI after OLT is J-shaped.
Do male engagement and couples’ communication influence maternal health care-seeking? Findings from a household survey in Mozambique
Authors: Sitefane Gilda G. , Banerjee Joya , Mohan Diwakar , Lee Connie S. , Ricca Jim , Betron Myra L. , Cuco Rosa Marlene Manjate
Published: June 2020

Background

This study explored effects of couples’ communication and male participation in birth preparedness and complication readiness (BPCR) on delivery in a health facility (“institutional delivery”). A cross-sectional, baseline household survey was conducted in November 2016 prior to an integrated maternal and child health project in Nampula and Sofala Provinces in Mozambique.

Methods

The study used the Knowledge, Practices and Coverage survey tool, a condensed version of the Demographic and Health Survey and other tools. The sample included 1422 women. Multivariable logit regression models tested the association of institutional delivery with couples’ communication and four elements of BPCR both with and without male partners: 1) saving money, 2) arranging transport, 3) choosing a birth companion, and 4) choosing a delivery site; controlling for partners’ attendance in antenatal care and social and demographic determinants (education, wealth, urban/rural location, and province).

Results

The odds that women would deliver in a health facility were 46% greater (adjusted odds ratio (aOR) = 1.46, 95% confidence interval (CI) = 1.02–2.10, p = 0.04) amongst women who discussed family planning with their partners than those who did not. Approximately half of this effect was mediated through BPCR. When a woman arranged transport on her own, there was no significant increase in institutional delivery, but with partner involvement, there was a larger, significant association (aOR = 4.31, 2.64–7.02). Similarly, when a woman chose a delivery site on her own, there was no significant association with institutional delivery (aOR 1.52,0.81–2.83), but with her partner, there was a larger and significant association (aOR 1.98, 1.16–3.36). Neither saving money nor choosing a birth companion showed a significant association with institutional delivery—with or without partner involvement. The odds of delivering in a facility were 28% less amongst poor women whose partners did not participate in BPCR than wealthy women, but when partners helped choose a place of delivery and arrange transport, this gap was nearly eliminated.

Conclusions

Our findings add to growing global evidence that men play an important role in improving maternal and newborn health, particularly through BPCR, and that couples’ communication is a key approach for promoting high-impact health behaviors.
Chronic respiratory symptoms, lung function and associated factors among flour mill factory workers in Hawassa city, southern Ethiopia: “comparative cross-sectional study”
Authors: Lagiso Zemachu Ashuro , Mekonnen Worku Tefera , Abaya Samson Wakuma , Takele Abera Kumie , Workneh Hailemichael Mulugeta
Published: June 2020

Background

Occupational related respiratory diseases arise as a result of the deposition of dust particles in the lungs. Flour milling industries; generate organic dust during industrial processes, such as cleaning, milling, packaging, and loading which release dust into the air and later inhaled by workers. Flour mill workers are at risk of developing respiratory health problems because of exposure in their working environment, but existing data were few. The aim of this study was to assess the prevalence of chronic respiratory symptoms, lung function and associated factors among flour mill factory workers.

Methods

A comparative cross-sectional study was conducted among 196 flour mill factory workers and 210 soft drinks factory workers. We selected study participants using a systematic sampling technique. We assessed the chronic respiratory symptoms using the questionnaire adopted from the British Medical Research Council. Binary logistic regression analysis with 95% CI and p < 0.05 was used to identify the factors. Lung function parameters; Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1) and ratio FEV1/FVC was measured by using spirometer and analyzed by using an independent t-test.

Results

We included 406 (96.7%) workers in this study. The prevalence of chronic respiratory symptoms was higher among flour mill workers as compared to soft-drinks factory workers (56.6% vs.12.9%). Primary education (AOR = 5.8, 95% CI, 1.3–23.2), mixing department (AOR = 5.3, 95% CI = 1.68–16.56), work experience 6–9 years (AOR = 5.1, 95% CI = 2.05–12.48), work experience ≥10 years (AOR = 2.5, 95% CI = 1.01–6.11) and working over eight hours (AOR = 2.4, 95% CI, 1.16–5.10) were factors that significantly associated with chronic respiratory symptoms among flour mill workers. FVC (p < 0.002), FEV1 (p < 0.001) and FEV1/FVC (p < 0.012) were significantly reduced among flour mill workers.

Conclusions

We found chronic respiratory symptoms to be high among flour mill workers. Lower education level, mixing department, increased work experience, and longer working hours were identified factors. The flour mill dust exposed worker’s lung function parameters were highly reduced. This study suggested that workers’ dust exposure reduction and control methods in flour mill factories need to be implemented.
Giant submandibular sialolipoma masquerading as huge goitre: a case report
Authors: Subramaniam Sentilnathan , Johan Syamim , Hayati Firdaus , Ng Chiak Yot , Azizan Nornazirah , Chuah Jitt Aun , Mohamad Irfan
Published: June 2020

Background

Sialolipoma is a rare tumour which may arise from both major and minor salivary glands and has recently been described as a variant of salivary gland lipomatous lesions.

Case presentation

We report a 54-year-old male who presented with a 7-year history of large right anterior neck swelling. He was clinically euthyroid and had no compressive or infiltrative symptoms. He sought medical attention due to the discomfort exerted by the weight of the mass and was keen for excision. The swelling appeared like a goitre but physical examination proved otherwise. Imaging was suggestive of a benign tumour arising from the right parapharyngeal fossa. The mass was surgically excised and was noted to be adherent to part of the submandibular gland. Histopathological examination revealed a new variant of benign adipocytic tumour of salivary gland or sialolipoma arising from the submandibular gland. Besides being the largest sialolipoma to be reported, there are also no reports of giant submandibular sialolipomas masquerading as a huge goitre in appearance.

Conclusion

Submandibular sialolipomas can present in really large sizes and appear as a giant goitre. It is important to differentiate between benign lipomas from liposarcomas and tailor the management accordingly. Surgical enucleation is the preferred choice of treatment for these benign tumours with low recurrence rates.
African potato (Hypoxis hemerocallidea): a systematic review of its chemistry, pharmacology and ethno medicinal properties
Authors: Matyanga Celia M. J. , Morse Gene D. , Gundidza Mazuru , Nhachi Charles F. B.
Published: June 2020

Background

African Potato (hypoxis hemerocallidea), is used for enhancing immune system in Southern Africa. It is among the plants of intense commercial and scientific interest; hence, the aim of this study was to describe its chemistry and pharmacology.

Methods

PubMed, Cochrane Controlled Trials Register (CENTRAL) and Google Scholar were searched independently for relevant literature. The last search occurred in October 2018. Other research material was obtained from Google. The following search terms were used, but not limited to: “African Potato”, “hypoxis”, “hemerocallidea”, “rooperol.” Articles that were explaining the chemistry and pharmacology of hypoxis hemerocallidea were included.

Results

Thirty articles from PubMed, Cochrane and Google Scholar were eligible. Three webpages were included from Google. Results showed that the tuberous rootstock (corm) of African Potato is used traditionally to treat wasting diseases, testicular tumours, insanity, barrenness, impotency, bad dreams, intestinal parasites, urinary infection, cardiac disease and enhancing immunity. The plant contains hypoxoside, which is converted rapidly to a potent antioxidant, rooperol in the gut. The corm contains sterols, sterol glycosides, stanols, terpenoids, saponins, cardiac glycosides, tannins and reducing sugars. A dose of 15 mg/kg/day of hypoxoside is reportedly therapeutic. Preclinical studies of African Potato have shown immunomodulation, antioxidant, antinociceptive, hypoglycaemic, anti-inflammatory, anticonvulsant, antibacterial, uterolytic, antimotility, spasmolytic and anticholinergic effects. The common side effects of African Potato are nausea and vomiting, which subside over time. In vitro, African Potato demonstrated inhibitory effects on CYP1A2, 2C9, 2D6, 3A4, 3A5, CYP19-metabolism and induction of P-glycoprotein. In vivo, it did not alter the pharmacokinetics of efavirenz or lopinavir/ritonavir.

Conclusion

African Potato is mainly used as an immunostimulant. The exact mechanisms of action for all the pharmacological actions are unknown. More research is required to substantiate claims regarding beneficial effects. There are many research gaps that require investigation including pharmacokinetic interactions with conventional drugs, especially those used in HIV/AIDS.
Isaria tenuipes Peck, an entomopathogenic fungus from Darjeeling Himalaya: Evaluation of in-vitro antiproliferative and antioxidant potential of its mycelium extract
Authors: Chhetri Dhani Raj , Chhetri Abhijit , Shahi Nerina , Tiwari Snigdha , Karna Shibendra Kumar Lal , Lama Dorjay , Pokharel Yuba Raj
Published: June 2020

Background

Isaria tenuipesis one of the potent species in the members of the genusIsaria, which is well reported to possess multiple bioactive substances of therapeutic importance. Therefore,an in vitro experimental study was carried to evaluate the bioactivities of the crude methanolic extract from the mycelium of this fungus.

Methods

The fungus was authenticated through morphological characters and the species discrepancy was resolved using the nuclear rDNA ITS sequence. The methanolic extract was fingerprinted by FTIR. The antioxidant components in terms of total phenols and flavonoids were determined as gallic acid and quercetin equivalents respectively. Antioxidant activities of the methanolic extract was assessed using 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2, 2/-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS0+), Fe2+chelating activity, and hydroxyl radical scavenging assays. Cytotoxicity of the extract was determined by [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] (MTT) assay on three cancer cell lines: HeLa, HepG2, and PC3. Apoptosis was further studied by propidium iodide (PI) and Annexin-V/PI staining flow cytometric analysis. Anti-proliferation capacity was studied by colony-forming assay.

Results

In the present study total phenol content of the dried methanol extract was 148.09 ± 3.51μg gallic acid equivalent/mg and flavonoid was 9.02±0.95 μg quercetin/mg. The antioxidant activities of methanol-water extract (8:2 v/v) from cultured mycelia ofI. tenuipesinvestigated and evaluated with 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay revealed IC50value of 5.04mg/ml with an inhibition rate of 74.77% at 10mg/ml and with an iron-chelating assay the chelating ability was recorded to be 86.76% where the IC50value was 4.43 mg/ml. In comparison among the antioxidant assays, 2,2/-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS0+) and hydroxyl assay exhibited radical scavenging rate of 44.42% and 49.82% respectively at a concentration of 10 mg/ml. The IC50value of the extract in MTT assay was 43.45μg/ml with HeLa cells, 119.33μg/ml with PC3 cells, and 125.55μg/ml with HepG2 cells.

Conclusion

In this study, it can be concluded that the crude methanolic extract exhibited potent antioxidant and antiproliferative activities suggesting natural antioxidative and antiproliferative agents.
Coverage, reporting degree and design of the Swedish quality registry for patients born with cleft lip and/or palate
Authors: Klintö Kristina , Karsten Agneta , Marcusson Agneta , Paganini Anna , Rizell Sara , Cajander Jenny , Brunnegård Karin , Hakelius Malin , Okhiria Åsa , Peterson Petra , Abdiu Avni , Havstam Christina , Mark Hans , Hagberg Emilie , Björnström Lena , Wiedel Anna-Paulina , Becker Magnus
Published: June 2020

Background

The objective of the Swedish cleft lip and palate (CLP) registry is to promote quality control, research and improvement of treatment, by comparison of the long-term results of surgery, orthodontics and speech from all six Swedish CLP centres. The purpose of the study was to investigate the coverage and reporting degree of the Swedish CLP registry, and to describe the design of the registry and discuss questions of reliability and validity of the data included.

Methods

All six Swedish CLP centres participate in the registry. All children in Sweden with cleft lip and/or cleft palate, born from 2009 onwards, are included in the registry. Baseline data such as cleft type (ICD-10 diagnosis), heredity, birth weight and additional deformities and/or syndromes, as well as pre-surgical treatment, are recorded at first visit. Data on surgical treatment are recorded continuously. Treatment outcome regarding dentofacial development and speech are recorded at follow-ups at 5, 10, 16 and 19 years of age. Data on dentofacial development are also recorded 1 year after orthognathic surgery. In addition, data on babbling and speech are recorded at 18 months of age. Coverage degree and reporting degree of surgery was assessed by comparison with registrations in the Swedish Central patient registry. Reporting degree of orthodontic and speech registrations at 5 years of age was assessed by comparison with registrations at baseline.

Results

The average coverage degree for children born 2009 to 2018 was 95.1%. For cleft-related surgeries, the average reporting degree was 92.4%. Average reporting degree of orthodontic registrations and speech registrations at age 5 years was 92 and 97.5% respectively.

Conclusion

In order to achieve valid and reliable data in a healthcare quality registry, the degree of coverage and reporting needs to be high, the variables included should be limited and checked for reliability, and the professionals must calibrate themselves regularly. The Swedish CLP registry fulfils these requirements.
Fuzzy cognitive mapping with Inuit women: what needs to change to improve cervical cancer screening in Nunavik, northern Quebec?
Authors: Tratt Elyse , Sarmiento Ivan , Gamelin Rachel , Nayoumealuk Jeannie , Andersson Neil , Brassard Paul
Published: June 2020

Background

Among Canadian Inuit, cervical cancer incidence and mortality rates are up to three times higher than the Canadian average. Cervical cancer is preventable through regular screening which, in Quebec, is opportunistic and requires physical examination and Papanicolaou (“Pap”) smears. Since Human Papillomavirus (HPV) is the necessary cause of cervical cancer, HPV testing is a plausible screening alternative. HPV testing by self-sampling also addresses several barriers associated with physical examination and access to healthcare. In a participatory research paradigm, we worked with two communities of Nunavik to explore the possible implementation of HPV self-sampling.

Method

Key community stakeholders formed an Advisory Committee to guide direct discussions with Inuit women. We presented available facts around cervical cancer, HPV and the female anatomy, and used Fuzzy Cognitive Mapping to collate women’s views. A thematic analysis summarized data, adding links and weights to represent the relationship of each factor on the outcome: screening for cervical cancer.

Results

According to the 27 Inuit women who participated, the most influential factor in using health services was the cultural awareness of the healthcare provider. A significant barrier to screening was patient lack of information. The principal vector of change – the factor most likely to influence other factors – was the means of communication between the healthcare provider and the patient: visual communication was told to be the most effective.

Conclusion

Fuzzy Cognitive Mapping is a practical tool for discussing possible health actions with stakeholders and to inform future research. The tool offers a visual aid for discussion across cultural and educational differences. It can help to build the partnerships that incorporate community voices into co-design of interventions that are relevant to and aligned with the needs of those who use them.
Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort
Authors: Snart Charles Jonathan Peter , Threapleton Diane Erin , Keeble Claire , Taylor Elizabeth , Waiblinger Dagmar , Reid Stephen , Alwan Nisreen A. , Mason Dan , Azad Rafaq , Cade Janet Elizabeth , Simpson Nigel A. B. , Meadows Sarah , McKillion Amanda , Santorelli Gillian , Waterman Amanda H. , Zimmermann Michael , Stewart Paul M. , Wright John , Mon-Williams Mark , Greenwood Darren Charles , Hardie Laura J.
Published: June 2020

Background

Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes.

Methods

Maternal iodine status was estimated from spot urine samples collected at 26–28 weeks’ gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score.

Results

There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies.

Conclusion

Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered.

Trial registration

ClinicalTrials.govNCT03552341. Registered on June 11, 2018.
Predictors of fatality including radiographic findings in adults with COVID-19
Authors: Li Kaiyan , Chen Dian , Chen Shengchong , Feng Yuchen , Chang Chenli , Wang Zi , Wang Nan , Zhen Guohua
Published: June 2020

Background

Older age and elevated d-dimer are reported risk factors for coronavirus disease 2019 (COVID-19). However, whether early radiographic change is a predictor of fatality remains unknown.

Methods

We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. Confirmed cases were defined by positive RT-PCR detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in throat-swab specimens. Chest CT images were reviewed independently by two radiologists. The Tongji Hospital ethics committee approved this study.

Results

A total of 102 patients were confirmed to have SARS-CoV-2 infection. As of March 25, 85 confirmed patients were discharged, 15 died, and 2 remained hospitalized. When compared with survivors, non-survivors were older (median age, 69 [interquartile range, 58–77] vs. 55 [44–66], p = 0.003), and more likely to have decreased lymphocyte count (0.5 vs. 0.9 ×  109/L, p = 0.006), elevated lactate dehydrogenase (LDH) (569.0 vs. 272.0 U/L, p < 0.001), elevated d-dimer (> 1 μg/mL, 86% vs. 37%, p = 0.002) on admission. Older age and elevated LDH were independent risk factors for fatality in a multivariate regression model included the above variables. In a subset of patients with CT images within the first week, higher total severity score, and more involved lung lobes (5 involved lobes) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients, higher total severity score was the only independent risk factor in a multivariate analysis incorporating the above mentioned variables.

Conclusions

Older age, elevated LDH on admission, and higher severity score of CT images within the first week are potential predictors of fatality in adults with COVID-19. These predictors may help clinicians identify patients with a poor prognosis at an early stage.
Metabolic engineering of Escherichia coli for efficient production of l-alanyl-l-glutamine
Authors: Zhu Jiangming , Yang Wei , Wang Bohua , Liu Qun , Zhong Xiaotong , Gao Quanxiu , Liu Jiezheng , Huang Jianzhong , Lin Baixue , Tao Yong
Published: June 2020

Background

l-Alanyl-l-glutamine (AQ) is a functional dipeptide with high water solubility, good thermal stability and high bioavailability. It is widely used in clinical treatment, post-operative rehabilitation, sports health care and other fields. AQ is mainly produced via chemical synthesis which is complicated, time-consuming, labor-intensive, and have a low yield accompanied with the generation of by-products. It is therefore highly desirable to develop an efficient biotechnological process for the industrial production of AQ.

Results

A metabolically engineered E. coli strain for AQ production was developed by over-expressing l-amino acid α-ligase (BacD) from Bacillus subtilis, and inactivating the peptidases PepA, PepB, PepD, and PepN, as well as the dipeptide transport system Dpp. In order to use the more readily available substrate glutamic acid, a module for glutamine synthesis from glutamic acid was constructed by introducing glutamine synthetase (GlnA). Additionally, we knocked out glsA–glsB to block the first step in glutamine metabolism, and glnE–glnB involved in the ATP-dependent addition of AMP/UMP to a subunit of glutamine synthetase, which resulted in increased glutamine supply. Then the glutamine synthesis module was combined with the AQ synthesis module to develop the engineered strain that uses glutamic acid and alanine for AQ production. The expression of BacD and GlnA was further balanced to improve AQ production. Using the final engineered strain p15/AQ10 as a whole-cell biocatalyst, 71.7 mM AQ was produced with a productivity of 3.98 mM/h and conversion rate of 71.7%.

Conclusion

A metabolically engineered strain for AQ production was successfully developed via inactivation of peptidases, screening of BacD, introduction of glutamine synthesis module, and balancing the glutamine and AQ synthesis modules to improve the yield of AQ. This work provides a microbial cell factory for efficient production of AQ with industrial potential.
Lipoprotein A, combined with alanine aminotransferase and aspartate aminotransferase, contributes to predicting the occurrence of NASH: a cross-sectional study
Authors: Zhang Yu , He He , Zeng Yu-Ping , Yang Li-Dan , Jia Dan , An Zhen-Mei , Jia Wei-Guo
Published: June 2020

Background

Nonalcoholic steatohepatitis (NASH) progresses from simple nonalcoholic fatty liver (NAFL) and has a poor prognosis. Abnormal lipid metabolism is closely related to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to study the relationships between serum lipid metabolites and NASH, and to improve the early diagnosis of NASH.

Methods

This study included 86 NAFLD patients (23 NASH and 63 NAFL), and 81 unaffected individuals as controls from West China Hospital between October 2018 and May 2019. With lipid metabolites as the focus of the study, the differences in lipid metabolites were compared between the control group, NAFL patients, and NASH patients. Logistic regression analysis was used to examine the risk factors of NASH. Finally, receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of the metabolites in NASH prediction.

Results

The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipoprotein A (LPA) increased with the severity of NAFLD. In NAFLD patients, LPA (OR:1.61; 95%CI: 1.03–2.52) was a potential risk factor for NASH, and ROC analysis showed that the combination of LPA, ALT, and AST had a greater predictive efficiency for NASH.

Conclusions

Abnormal apolipoprotein/lipoprotein is closely related to lipid metabolism disorder in patients with NAFLD. In NAFL, the combination of LPA, ALT, and AST contributes to predicting the occurrence of NASH. LPA may be a potential biomarker and therapeutic target for diagnosing and treating NASH.
A qualitative exploration of the content and face validity of preference-based measures within the context of dementia
Authors: Engel Lidia , Bucholc Jessica , Mihalopoulos Cathrine , Mulhern Brendan , Ratcliffe Julie , Yates Mark , Hanna Lisa
Published: June 2020

Background

Assessing the cost-effectiveness of interventions for people with dementia, based on cost per quality-adjusted life years (QALYs) gained, requires that the measures used to derive QALYs are preference-based whilst also being valid, feasible to use, comprehensible and acceptable for people with dementia. The aim of this study was to assess the content and face validity of six preference-based measures (PBMs) within the context of dementia.

Methods

Qualitative focus groups and interviews were conducted with community-dwelling individuals with mild dementia and carers of people with dementia. After exploring participants’ understanding of ‘quality of life’ (QoL), six PBMs were assessed for content and face validity: two measures assessing health-related QoL (EQ-5D-5L and AQoL-8D); two covering broader aspects of capability wellbeing and social care-related QoL (ICECAP-O and ASCOT); and two dementia-specific QoL measures (DEMQOL-U and AD-5D). A random mix of one health-related QoL measure, one wellbeing measure, and one dementia-specific measure was explored in each session. All sessions were audiotaped and transcribed verbatim. Data were analysed thematically.

Results

Nine individuals with mild dementia and 17 carers of people with dementia participated across 4 focus groups and 10 interviews. Participants perceived 9 broad QoL domains as relevant to them: Activity, Autonomy, Cognition, Communication, Coping, Emotions, End-of-Life, Physical Functioning, and Relationships. These domains had limited overlap with the content of the six PBMs. Assessment of face validity was summarized into eight themes: (1) ambiguous questions, (2) double –barrelled questions, (3) difficult/abstract questions, (4) judgemental/confronting questions, (5) lack of relevance and comprehensiveness, (6) response options, (7) layout/format and (8) proxy-response. There was no clear preference for one of the six measures explored; participants identified advantages and disadvantages across all measures. Although particularly designed for individuals with dementia, dementia-specific QoL measures were not always favoured over non-specific measures.

Conclusion

Given the shortcomings of PBMs identified in this study, further empirical comparative analyses are necessary to guide the selection of PBMs for future dementia research.
Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies?
Authors: Leigh Natasha , Solomon Daniel , Pletcher Eric , Labow Daniel M. , Magge Deepa R. , Sarpel Umut , Golas Benjamin J.
Published: June 2020

Background

Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies: hepatocellular carcinoma 11 months with sorafenib, and pancreaticobiliary 9–14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients.

Methods

We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007 to 2017 and analyzed perioperative and oncologic outcomes.

Results

Seventeen patients were included: 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). Peritoneal cancer index, number of organs resected, completeness of cytoreduction, and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%,p= 0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months,p= 0.206) with 59% 3-year overall survival (vs. 0% cholangiocarcinoma, 0% gallbladder, 0% pancreatic).

Conclusions

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.
Effects of concomitant use of prasugrel with edoxaban on bleeding time, pharmacodynamics, and pharmacokinetics of edoxaban in healthy elderly Japanese male subjects: a clinical pharmacology study
Authors: Ikushima Ippei , Akasaka Takaaki , Morishima Yoshiyuki , Takita Atsushi , Motohashi Tomoko , Kimura Tetsuya
Published: June 2020

Background

Dual therapy with a direct oral anticoagulant (DOAC) plus a P2Y12receptor inhibitor is recommended in patients with nonvalvular atrial fibrillation who undergo percutaneous coronary intervention. Thus, we evaluated the effects of DOAC edoxaban plus P2Y12receptor inhibitor prasugrel on bleeding time (BT), and pharmacodynamics (PD) and pharmacokinetics (PK) of edoxaban in healthy elderly Japanese male subjects.

Methods

A single-center, clinical pharmacology study with randomized, open-label, repeated dosing enrolled 24 participants in two groups of 12 receiving 30 mg edoxaban once daily for 3 days; then 30 mg edoxaban plus 2.5 mg prasugrel (Group 1) or 30 mg edoxaban plus 3.75 mg prasugrel (Group 2) once daily for 5 days. Primary endpoint was BT by the Ivy method. Secondary endpoints were the PD parameters of prothrombin time (PT), activated partial thromboplastin time (aPTT), prothrombin fragment F1 + 2 (F1 + 2), and P2Y12reaction units (PRU), and PK profiles of edoxaban alone and in combination with prasugrel.

Results

Geometric least squares mean of BT ratios (vs. baseline) for 3-day edoxaban treatment were 1.097 (90% confidence interval (CI) 0.911–1.321) in Group 1 and 1.327 (90% CI 1.035–1.703) in Group 2; for 5-day edoxaban plus 2.5 mg and 3.75 mg prasugrel, they were 1.581 (90% CI 1.197–2.087) and 1.996 (90% CI 1.482–2.690), respectively. Contributions of prasugrel to the effects (edoxaban + prasugrel/edoxaban) were 1.442 (90% CI 1.096–1.897) in Group 1 and 1.504 (90% CI 1.172–1.930) in Group 2. Edoxaban prolonged PT and aPTT and decreased F1 + 2. Adding on prasugrel did not appreciably change PT, aPTT, or F1 + 2. Prasugrel reduced PRU, whereas edoxaban had no effect on PRU. We recorded 26 adverse events; 23 were treatment-emergent (positive fecal occult blood test). All participants with adverse events recovered during follow-up.

Conclusions

Coadministration of 2.5 mg and 3.75 mg prasugrel with 30 mg edoxaban prolonged BT in healthy elderly Japanese male subjects. The effect was dependent on the dose of prasugrel. Prasugrel did not affect PD or PK profiles of edoxaban. Edoxaban had no effect on PD of prasugrel.

Trial registration

Japan Registry of Clinical Trials No.jRCTs071190006; registration date, 26-April-2019.
Multisector nutrition gains amidst evidence scarcity: scoping review of policies, data and interventions to reduce child stunting in Afghanistan
Authors: Kim Christine , Mansoor Ghulam Farooq , Paya Pir Mohammad , Ludin Mohammad Homayoun , Ahrar Mohammad Javed , Mashal Mohammad Omar , Todd Catherine S.
Published: June 2020

Background

Child health indicators have substantially improved across the last decade, yet Afghanistan has among the highest child stunting and malnutrition rates in Asia. Multisectoral approaches were recently introduced but evidence for this approach to improve support for and implementation of child nutrition programmes is limited compared to other countries.

Methods

We reviewed policy and programme data to identify best practices and gaps surrounding child malnutrition in Afghanistan. We conducted a scoping review using broad search categories and approaches, including database and website searches, reference hand-searches, purposive policy and programme document request, and key informant interviews. Inclusion and exclusion criteria were developed iteratively, with abstracts and documents assessed against the final criteria. We abstracted documents systematically and summarised and synthesised content to generate the main findings.

Results

We included 18 policies and strategies, 45 data sources and reports, and 20 intervention evaluations. Movement towards multisectoral efforts to address malnutrition at the policy level has started; however, integrated nutrition-specific and nutrition-sensitive interventions are not yet uniformly delivered at the community level. Many data sources capturing nutrition, food security and WASH (water, sanitation and hygiene) indicators are available but indicator definitions are not standardised and there are few longitudinal nutrition surveys. Political will to improve household nutrition status has shown increased government and donor investments in nutrition-sensitive and nutrition-specific programmes through combined small- and large-scale interventions between 2004 and 2013; however, evidence for interventions that effectively decrease stunting prevalence is limited.

Conclusions

This review shows a breadth of nutrition programme, policy and data in Afghanistan. Multisector approaches faced challenges of reaching sufficient coverage as they often included a package of food security, livelihoods and health interventions but were each implemented independently. Further implementation evidence is needed to aid policy and programmes on effective integration of nutrition, food security and WASH in Afghanistan.
PINOT: an intuitive resource for integrating protein-protein interactions
Authors: Tomkins James E. , Ferrari Raffaele , Vavouraki Nikoleta , Hardy John , Lovering Ruth C. , Lewis Patrick A. , McGuffin Liam J. , Manzoni Claudia
Published: June 2020

Background

The past decade has seen the rise of omics data for the understanding of biological systems in health and disease. This wealth of information includes protein-protein interaction (PPI) data derived from both low- and high-throughput assays, which are curated into multiple databases that capture the extent of available information from the peer-reviewed literature. Although these curation efforts are extremely useful, reliably downloading and integrating PPI data from the variety of available repositories is challenging and time consuming.

Methods

We here present a novel user-friendly web-resource called PINOT (Protein Interaction Network Online Tool; available athttp://www.reading.ac.uk/bioinf/PINOT/PINOT_form.html) to optimise the collection and processing of PPI data from IMEx consortium associated repositories (members and observers) and WormBase, for constructing, respectively, human andCaenorhabditis elegansPPI networks.

Results

Users submit a query containing a list of proteins of interest for which PINOT extracts data describing PPIs. At every query submission PPI data are downloaded, merged and quality assessed. Then each PPI is confidence scored based on the number of distinct methods used for interaction detection and the number of publications that report the specific interaction. Examples of how PINOT can be applied are provided to highlight the performance, ease of use and potential utility of this tool.

Conclusions

PINOT is a tool that allows users to survey the curated literature, extracting PPI data in relation to a list of proteins of interest. PINOT extracts a similar numbers of PPIs as other, analogous, tools and incorporates a set of innovative features. PINOT is able to process large queries, it downloads human PPIs live through PSICQUIC and it applies quality control filters on the downloaded PPI data (i.e. removing the need for manual inspection by the user). PINOT provides the user with information on detection methods and publication history for each downloaded interaction data entry and outputs the results in a table format that can be straightforwardly further customised and/or directly uploaded into network visualization software.
Oxygenated polycyclic aromatic hydrocarbons from ambient particulate matter induce electrophysiological instability in cardiomyocytes
Authors: Ju Sujin , Lim Leejin , Jiao Han-Yi , Choi Seok , Jun Jae Yeoul , Ki Young-Jae , Choi Dong-Hyun , Lee Ji yi , Song Heesang
Published: June 2020

Background

Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. However, the cellular and molecular mechanisms by which PM exposure causes arrhythmia and the component that is mainly responsible for this adverse effect remains to be established. In this study, the arrhythmogenicity of mobilized organic matter from two different types of PM collected during summer (SPM) and winter (WPM) seasons in the Seoul metropolitan area was evaluated. In addition, differential effects between polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs) on the induction of electrophysiological instability were examined.

Results

We extracted the bioavailable organic contents of ambient PM, measuring 10 μm or less in diameter, collected from the Seoul metropolitan area using a high-volume air sampler. Significant alterations in all factors tested for association with electrophysiological instability, such as intracellular Ca2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca2+-regulating proteins, sarcoplasmic reticulum Ca2+ATPase (SERCA2a), Ca2+/calmodulin-dependent protein kinase II (CaMK II), and ryanodine receptor 2 (RyR2) were observed in cardiomyocytes treated with PM. Moreover, the alterations were higher in WPM-treated cardiomyocytes than in SPM-treated cardiomyocytes. Three-fold more oxy-PAH concentrations were observed in WPM than SPM. As expected, electrophysiological instability was induced higher in oxy-PAHs (9,10-anthraquinone, AQ or 7,12-benz(a) anthraquinone, BAQ)-treated cardiomyocytes than in PAHs (anthracene, ANT or benz(a) anthracene, BaA)-treated cardiomyocytes; oxy-PAHs infusion of cells mediated by aryl hydrocarbon receptor (AhR) was faster than PAHs infusion. In addition, ROS formation and expression of calcium-related genes were markedly more altered in cells treated with oxy-PAHs compared to those treated with PAHs.

Conclusions

The concentrations of oxy-PAHs in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the ROS generation and disruption of calcium regulation.
Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice
Authors: Coméra Christine , Cartier Christel , Gaultier Eric , Catrice Olivier , Panouille Quentin , El Hamdi Sarah , Tirez Kristof , Nelissen Inge , Théodorou Vassilia , Houdeau Eric
Published: June 2020

Background

Food-grade TiO2 (E171 in the EU) is widely used as a coloring agent in foodstuffs, including sweets. Chronic dietary exposure raises concerns for human health due to proinflammatory properties and the ability to induce and promote preneoplastic lesions in the rodent gut. Characterization of intestinal TiO2 uptake is essential for assessing the health risk in humans. We studied in vivo the gut absorption kinetics of TiO2 in fasted mice orally given a single dose (40 mg/kg) to assess the ability of intestinal apical surfaces to absorb particles when available without entrapment in the bolus. The epithelial translocation pathways were also identified ex vivo using intestinal loops in anesthetized mice.

Results

The absorption of TiO2 particles was analyzed in gut tissues by laser-reflective confocal microscopy and ICP-MS at 4 and 8 h following oral administration. A bimodal pattern was detected in the small intestine: TiO2 absorption peaked at 4 h in jejunal and ileal villi before returning to basal levels at 8 h, while being undetectable at 4 h but significantly present at 8 h in the jejunal Peyer’s patches (PP). Lower absorption occurred in the colon, while TiO2 particles were clearly detectable by confocal microscopy in the blood at 4 and 8 h after treatment. Ex vivo, jejunal loops were exposed to the food additive in the presence and absence of pharmacological inhibitors of paracellular tight junction (TJ) permeability or of transcellular (endocytic) passage. Thirty minutes after E171 addition, TiO2 absorption by the jejunal villi was decreased by 66% (p < 0.001 vs. control) in the presence of the paracellular permeability blocker triaminopyrimidine; the other inhibitors had no significant effect. Substantial absorption through a goblet cell (GC)-associated pathway, insensitive to TJ blockade, was also detected.

Conclusions

After a single E171 dose in mice, early intestinal uptake of TiO2 particles mainly occurred through the villi of the small intestine, which, in contrast to the PP, represent the main absorption surface in the small intestine. A GC-associated passage and passive diffusion through paracellular TJ spaces between enterocytes appeared to be major absorption routes for transepithelial uptake of dietary TiO2.
Angiogenesis in mammary Paget disease: histopathological analyses of blood vessel density and angiogenic factors
Authors: Akishima-Fukasawa Yuri , Honma Naoko , Ogata Hideaki , Akasaka Yoshikiyo , Mikami Tetuo
Published: June 2020

Background

We examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging. The relationships among blood vessel density (BVD), histopathological parameters of blood flow in the nipple, and the expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were examined.

Methods

We calculated the average CD34-positive BVD and podoplanin (D2–40)-positive lymphatic vessel density (LVD) and the proportion of proliferating of endothelial cells in 14 Paget disease, 3 dermatitis biopsy, and 14 age-matched control cases. As a parameter related to blood flow in the nipple, the total CD34-positive blood vessel lumen area relative to the entire nipple area was measured in each Paget disease and control case using an automated image analysis system. Immunohistochemical expression of bFGF and VEGFA in Paget cells was also examined.

Results

The average BVD and LVD were significantly higher in the Paget disease cases than in the dermatitis (p = 0.003) and control (p < 0.001) cases. The proportion of proliferating endothelial cells was also increased in the Paget disease cases. The ratio of the CD34-positive blood vessel lumen area to nipple area was also significantly higher in the Paget disease than control cases (p = 0.003). The average BVD was correlated with the average LVD (r = 0.734, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.692, p < 0.001). Immunohistochemical expression of bFGF was strong in all Paget disease cases, with a significantly higher expression score in the Paget disease than dermatitis (p = 0.003) and control (p < 0.001) cases. The bFGF, but not VEGFA, expression score, was strongly correlated with the average BVD (r = 0.818, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.503, p = 0.006).

Conclusion

These results provide direct histopathological evidence of a marked increase in nipple blood flow in Paget disease detected by clinical imaging. bFGF is considered to play a pivotal role in angiogenesis in mammary Paget disease.