bluuebunny/crossref_metadata_2025 huggingface dataset:
Cambio organizacional: un modelo que dinamiza la transformación
Authors: Fierro-Celis Fernando Adolfo
Published: July 2020

Rev.esc.adm.neg

El objetivo de este artículo es proponer un nuevo modelo de cambio organizacional o CO basado en teorías contemporáneas que puedan suplir el enfoque de los antiguos modelos de CO, con lo que se pretende desarrollar un nuevo marco conceptual. Se busca que esta propuesta ayude, de manera amplia, a entender las transformaciones y los momentos por los que atraviesan las organizaciones en los procesos de cambio; y que a su vez se convierta en una herramienta que permita ubicar al director ejecutivo en el camino a seguir frente a los posibles escenarios que se puedan presentar en dicho proceso. El modelo, presentado de modo holístico tiene en cuenta los diferentes factores de cambio: individuo-organización-entorno, y sugiere cinco procesos claves: identificación de la estrategia, valor de la organización, personal de la empresa, manejo de la información y evaluación del desempeño; de esta manera, el gerente general puede establecer el anclaje de cambio y, a partir de él, el proceso eficiente en la trasformación de la empresa. Se concluye que el modelo es una nueva alternativa, susceptible a la interpretación, la aplicación, el cuestionamiento y el mejoramiento, que puede convertirse en una herramienta útil para instituciones que están en contextos turbulentos y de incertidumbre, ya que pueden establecer el direccionamiento desde cualquier arista establecida por el modelo sin que sea necesario que se desarrolle en su totalidad, pues lo importante es la capacidad de respuesta rápida.
A blended eHealth intervention for insomnia following acquired brain injury study protocol for a randomized controlled trial
Authors: Ford Marthe , Geurtsen Gert J. , Groet Erny , Bennekom Coen A.M. Van , Someren Eus J.W. Van
Published: July 2020

Background: Up to a third of stroke patients and patients with traumatic brain injury suffer from insomnia, including problems to fall asleep or stay asleep at night. Insomnia may exacerbate other brain damage-related problems, for example regarding cognitive functioning and emotional well-being, may lead to poorer quality of life, and may complicate recovery processes. Cognitive behavioural therapy for insomnia, delivered face-to-face or online, is found to be effective in the general population. However, despite the high prevalence and serious consequences of insomnia following acquired brain injury, studies on the efficacy of face-to-face cognitive behavioural treatment in this population are scarce, and this applies even more for studies on online cognitive behavioural therapy. Therefore, this study aims to evaluate the efficacy of a newly developed guided online cognitive behavioural therapy for insomnia following acquired brain injury.Methods: A multicenter randomized controlled trial will be conducted, in which 48 patients diagnosed with stroke or traumatic brain injury, and insomnia will be randomly allocated to the online cognitive behavioural therapy for insomnia treatment group or the treatment as usual group. The treatment consists of 6 online cognitive behavioural therapy sessions given on a weekly basis and personalized feedback after each session, combined with 2 face-to-face sessions. Outcomes will be assessed at baseline, immediately after the intervention period and at 6 weeks follow up. The primary outcome is the insomnia severity assessed with the insomnia severity index. Secondary outcome measures include sleep quality, sleep features derived from the sleep diary, fatigue, anxiety and depression, subjective cognitive functioning and societal participation.Discussion: This study will provide insight on the efficacy of online cognitive behavioural therapy for insomnia following stroke and traumatic brain injury.Trial Register: Netherlands Trial Register, NTR7082, 12 March 2018
Adoption Rates of Electronic Health Records in Turkish Hospitals and the Relation with Hospital Sizes
Authors: Kose Ilker , Rayner John , Birinci Suayip , Ulgu Mustafa Mahir , Yilmaz Ismayil , Guner Seyma
Published: July 2020

Background : Nation-wide adoption of electronic health records (EHRs) in hospitals has become a Turkish policy priority in recognition of their benefits in maintaining the overall quality of clinical care. The electronic medical record maturity model (EMRAM) is a widely used survey tool developed by the Healthcare Information and Management Systems Society (HIMSS) to measure the rate of adoption of EHR functions in a hospital or a secondary care setting. Turkey completed many standardizations and infrastructural improvement initiatives in the health information technology (IT) domain during the first phase of the Health Transformation Program between 2003 and 2017. Like the United States of America (USA), the Turkish Ministry of Health (MoH) applied a bottom-up approach to adopting EHRs in state hospitals. This study aims to measure adoption rates and levels of EHR use in state hospitals in Turkey and investigate any relationship between adoption and use and hospital size. Methods : EMRAM surveys were completed by 600 (68.9%) state hospitals in Turkey between 2014 and 2017. The availability and prevalence of medical information systems and EHR functions and their use were measured. The association between hospital size and the availability/prevalence of EHR functions was also calculated. Results: We found that 63.1% of all hospitals in Turkey have at least basic EHR functions, and 36% have comprehensive EHR functions, which compares favourably to the results of Korean hospitals in 2017, but unfavorably to the results of US hospitals in 2015 and 2017. Our findings suggest that smaller hospitals are better at adopting certain EHR functions than larger hospitals. Conclusion: Measuring the overall adoption rates of EHR functions is an emerging approach and a beneficial tool for the strategic management of countries. This study is the first one covering all state hospitals in a country using EMRAM. The bottom-up approach to adopting EHR in state hospitals that was successful in the USA has also been found to be successful in Turkey. The results are used by the Turkish MoH to disseminate the nation-wide benefits of EHR functions.
Liquid-based Cytology for the Detection of Cervical Intraepithelial Lesions in Jimma Town, Ethiopia
Authors: Tesfaw Getnet , Ahmed Yesuf , Gedefaw Lealem , Dube Lamessa , Godu Samson , Eshetu Kirubel , Nigussie Mesfin , Hailekiros Haftamu , Joloba Moses , Goba Gelila Kidane , Abdissa Alemseged
Published: July 2020

Background: Cervical cancer is the second leading type of female cancer in Ethiopia. Screening for cervical cancer is primarily conducted using visual inspection with 5% acetic acid (VIA). Liquid-based cytology (LBC) is not yet widely used in Ethiopia. Method: Women aged 21-65 years were tested using LBC and VIA to detect cervical dysplasia. Logistic regression analysis was conducted to identify associated factors. Cohen’s Kappa test was conducted to test agreement between LBC and VIA. Results: Forty-two percent (n=188) of 448 participants were 31 to 40 years of age and only two participants were above 60. Of the 448 participants, 419 (93.5%) were tested with LBC, 294 (65.6%) VIA and 272 (60.7%) with both LBC and VIA. Among women screened using LBC, 305 (72.8%) were negative for intraepithelial lesion or malignancy (NILM), 97 (23.2%) had low-grade squamous intraepithelial lesion (LSIL) and 17 (4.1%) had high-grade squamous intraepithelial lesion (HSIL). Presence of cervical lesions was generally lower in younger and older women. Majority, 39 (40%) of women with LSIL and 10 (59%) with HSIL were 41-50 years of age. Women aged 51-60 were more likely to have abnormal intraepithelial lesions compared to women aged 21-30 (AOR= 20.9, 95% CI=[7.2-60.9], p=0.00). Out of 47 (10.8%) HIV-positive women, 14 (32.56%) had intraepithelial lesions of which 10 (23.3%) and 4 (9.3%) had LSIL and HSIL, respectively. Among women screened with VIA, 18 (6.1%) were positive; among the 272 (60.7%) women screened using both LBC and VIA, 6 (2.2%) were positive on both LBC and VIA tests. The level of agreement between the two tests was weak at a statistically significant level (kappa value=0.155, p=0.006). Conclusion: LBC demonstrated high rates of cervical squamous intra-epithelial lesions in our study. VIA was a less reliable predictor of cervical squamous intra-epithelial lesions than LBC. Evaluating diagnostic accuracy of both LBC and VIA against a histological endpoint should be completed before adopting either or both screening modalities.
Interventions for prudent antibiotic use in primary healthcare: An econometric analysis
Authors: Lampi Elina , Carlsson Fredrik , Sundvall Pär-Daniel , Torres Marcela Jaime , Ulleryd Peter , Åhrén Christina , Jacobsson Gunnar
Published: July 2020

Background

Rational antibiotic prescribing is crucial to combat antibiotic resistance. Optimal strategies to improve antibiotic use are not known. Strama, the Swedish strategic program against antibiotic resistance, has been successful in reducing antibiotic prescription rates. This study investigates whether two specific interventions directed toward healthcare centers, an informational visit and a self-evaluation meeting, played a role in observed reduction in rates of antibiotic prescriptions in primary healthcare.

Methods

The study was a retrospective, observational, empirical analysis exploiting the variation in the timing of the interventions and considering past prescriptions through use of estimations from dynamic panel data models. Primary healthcare data from 2011 to 2014 were examined. Data were from public and private primary healthcare centers in western Sweden. The key variables were prescription of antibiotics and indicator variables for the two interventions.

Results

The first intervention, an educational information intervention, decreased the number of prescriptions among public healthcare centers, but this effect was only temporary. We found no proof that the second intervention, a self-evaluation meeting at the healthcare center, had an impact on the reduction of prescriptions.

Conclusions

Single educational interventions aimed at influencing rates of antibiotic prescriptions have limited impact. A multifaceted approach is needed in efforts to reduce the use of antibiotics in primary health care.
Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study
Authors: Zheng Yang , Wu Jie , Ding Cheng , Xu Kaijin , Yang Shigui , Li Lanjuan
Published: July 2020

Background: Chronic hepatitis B has become a major public health problem in China. An accurate depiction of the disease burden has not yet been thoroughly conducted. We aimed to project the disease burden of chronic hepatitis B virus (HBV) infection and related complications by modeling various scenarios. Method : An individual-based Markov model was used to predict disease burden from 2006 through 2050. We simulated 5 scenarios with different annual incidences, diagnoses and nucleotide analog (NA) treatment rates as well as treatment eligibility, which included a natural history without diagnosis or NA therapy, a base case, a World Health Organization-proposed target case and two ideal cases. Result: The natural history scenario is projected to have the fewest HBsAg losses (27.59 million) and highest number of HBV-related deaths (27.19 million). With improved diagnosis and treatment rates of NA therapy, ideal cases have fewer HBV-related deaths (14.46-14.77 million) than do WHO-proposed cases (15.13 million) and base cases (16.89 million), but the proportion of HBsAg loss is similar among them. With a reduction in new infections, the prevalence of chronic HBV in 2050 is expected to be a minimum of 27.03-27.49 million under WHO and ideal cases. Conclusion: Ideal scenarios 1 and 2 contribute to the lowest disease burden of HBV and its complications in the future, in which new infection control is more effective than increasing diagnosis, treatment rate and treatment eligibility. However, considering the large existing chronic HBV infected population and the low HBsAg loss rate of NA therapy, it is still difficult to avert the increasing trend of cumulative cirrhosis, DC, HCC, LT, and HBV-related death in all scenarios. If new high-potency drugs are not developed, the disease burden of chronic HBV will remain high in the future.
Self-assessed competence and need for further training among registered nurses in somatic hospital wards in Sweden: a cross-sectional survey
Authors: Allvin Renée , Bisholt Birgitta , Blomberg Karin , Bååth Carina , Wangensteen Sigrid
Published: July 2020

Background: Professional competence and continuous professional development is essential for ensuring high quality and safe nursing care, and it might be important for motivating nurses to stay in the profession. Thus, there is a need to identify the developmental process of nursing competency. Assessment of competence and need for further training helps to identify areas for quality improvement, and to design interventions in order to facilitate continuous competence development in different work contexts. The current study aimed to 1) describe registered nurses’ self-assessment of clinical competence as well as the need for further training, and 2) explore possible differences between registered nurses with varying lengths of professional experience as a nurse (≤ 0.5 year, >0.5-5 years, and ≥ 6 years).Methods: A cross-sectional survey design was applied, using the Professional Nurse Self-Assessment Scale of clinical core competencies II. Registered nurses (n=267) working in medical and surgical contexts in hospitals in Sweden responded (response rate 51 %). Independent student t-test and analysis of variance were carried out.Results: Registered nurses assessed their competence highest in statements related to cooperation with other health professionals; taking full responsibility; and acting ethically. They assessed their need for further training most for statements related to assessing patients’ health needs by telephone; giving health promotion advice and recommendations to patients by telephone; as well as improving a creative learning environment for staff at the workplace. For self-assessed competence and need for further training, differences between the groups for 35 and 46 items respectively, out of 50 were statistically significant.Conclusions: Although the registered nurses assessed their competence high for important competence components expected of professionals such as cooperation with other healthcare professionals, it is problematic that knowledge of interactions and side-effects of different types of medication were reported as having the highest need of training. Longitudinal follow up of newly graduated nurses regarding their continuous development of competence as well as further training is needed.
Effects of oncological care pathways in primary and secondary care on patient, professional and health systems outcomes: a systematic review and meta-analysis
Authors: Hoeve Jolanda C. van , Vernooij Robin W.M. , Fiander Michelle , Nieboer Peter , Siesling Sabine , Rotter Thomas
Published: July 2020

Background: Pathways are frequently used to improve care for cancer patients. However, there is little evidence about the effects of pathways used in oncological care. Therefore, we performed a systematic review and meta-analysis aiming to identify, and synthesise existing literature on the effects of pathways in oncological care. Methods: All patients diagnosed with cancer in primary and secondary/tertiary care whose treatment can be characterized as the strategy “care pathways” are included in this review. A systematic search in seven databases was conducted to gather evidence. Studies were screened by two independent reviewers. Study outcomes regarding patients, professionals and system level were extracted from each study. Results: Out of 13,847 search results, we selected 158 articles eligible for full text assessment. 150 studies were excluded and the remaining eight studies represented 4,786 patients. Most studies were conducted in secondary/tertiary care. LOS was the most common used indicator, and was reported in five studies. Meta-analysis based on subgroups showed an overall shorter Length of Stay (LOS) regarding gastric cancer (Weighted Mean Difference (WMD)): -2.75, CI: -4.67–-0.83) and gynaecological cancer (WMD: -1.58, CI: -2.10–-1.05). Costs were reported in six studies and most studies reported lower costs for pathway groups. Conclusions: Despite the differences between the included studies, we were able to present an evidence base for cancer care pathways performed in secondary/tertiary care regarding the positive effects of LOS in favour of cancer care pathways. Systematic review registration: PROSPERO CRD42017057592
Identification and validation of a commercial cryopreservation medium for the practical preservation of Dirofilaria immitis microfilaria
Authors: Shirozu Takahiro , Soga Akira , Fukumoto Shinya
Published: July 2020

Background

Dirofilaria immitis is a parasitic nematode transmitted by mosquitoes and the cause of heartworm disease in dogs and dirofilariasis in humans and other mammals. The parasite is endemic worldwide. Vector stage research requires a reliable supply of D. immitis microfilariae (mf). It is believed that cryopreserved mf would retain viability and provide a powerful tool for vector stage research. However, reports on cryopreservation of D. immitis mf are limited. Therefore, this study aimed to validate commercial cryopreservation media to establish a practical, convenient, and reproducible storage procedure for D. immitis mf.

Methods

Six different commercially available cryopreservation media were compared with the traditional polyvinylpyrrolidone-dimethyl sulfoxide (PVP-DMSO) preservation solution. In vitro viability of purified D. immitis mf and mf-infected total blood was analyzed using a motility assay and propidium iodide staining. In vivo infectivity of Aedes aegypti mosquitoes with cryopreserved mf was assessed using a mosquito survival test and quantifying the number of infective third stage larvae (L3) after 13 d post-infection.

Results

Purified mf cryopreserved in CultureSure showed the best viability when compared to mf cryopreserved in the remaining five commercially available media and PVP-DMSO. Viability of mf in mf-infected total blood cryopreserved in CultureSure varied with the ratio of infected blood to CultureSure. Optimum results were obtained with 200 µL mf-infected blood:800 µl CultureSure. CultureSure was also the optimum medium for cryopreserving mf prior to infectivity of Ae. aegypti. The number of L3 was approximately the same for CultureSure cryopreserved mf (3×-concentrated solution) and non-cryopreserved fresh mf.

Conclusions

CultureSure is an optimal commercial cryopreservation solution for the storage of D. immitis purified mf, mf-infected total blood, and mf used for in vivo mosquito experiments. Furthermore, this study describes an easy preservation method for clinical D. immitis -infected blood samples facilitating vector stage studies, as well as the education of veterinarians.
Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2
Authors: Cheng Liang , Cao Huifeng , Xu Jianbo , Xu Mo , He Wenjie , Zhang Wenjing , Dong Longxin , Chen Dayin
Published: July 2020

Background

Clear cell renal cell carcinoma (CCRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for CCRCC. This research aims to disclose the involvement of circRNA ribosomal protein L23a (circ_RPL23A) in CCRCC, and how it regulates carcinogenesis.

Methods

We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cellular behavior detection included cell cycle, proliferation, apoptosis and metastasis, which were severally analyzed using propidium iodide (PI)-flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), Annexin V/PI-flow cytometry and transwell migration/invasion assays. ACAT2 and related proteins of cell cycle, epithelial-mesenchymal transition (EMT) were measured via western blot. Target relationship was analyzed via dual-luciferase reporter assay. A xenograft model was used to study circ_RPL23A action in mice.

Results

Both in CCRCC tissues and cells, circ_RPL23A had a down-regulated tendency. Explicitly, circ_RPL23A overexpression inhibited cell cycle, proliferation and metastasis but enhanced apoptosis of CCRCC cells, whereas these effects of circ_RPL23A were dependent on the suppression of its target miR-1233. Besides, miR-1233 could target ACAT2 and circ_RPL23A regulated ACAT2 by sponging miR-1233. Also importantly, miR-1233 was a pro-cancer gene in CCRCC via targeting ACAT2. CCRCC tumor growth was also decreased in vivo by circ_RPL23A through miR-1233/ACAT2 axis.

Conclusion

Altogether, the circ_RPL23A/miR-1233/ACAT2 axis in this report provides an in-depth cognition for CCRCC pathogenesis and circ_RPL23A may has pivotal value in diagnosing and treating CCRCC.
Association between adipokines and thyroid carcinoma: a meta-analysis of case-control studies
Authors: Zhao Junyu , Wen Jing , Wang Shengnan , Yao Jinming , Liao Lin , Dong Jianjun
Published: July 2020

Background: The incidence of thyroid carcinoma is increasing all over the world. Some studies have suggested that the change of adipokines expression can induce thyroid carcinoma. However, other studies have come to the opposite conclusion. Therefore, we studied the relationship between adipokines and thyroid carcinoma. Methods: Databases—PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries were searched. A meta-analysis was performed when heterogeneity analysis show a good homogeneity. Results: Twenty-nine articles were finally included for analysis. The level of serum tumor necrosis factor-alpha (TNF-α) [standardized mean difference (SMD) =1.31, 95% confidence interval (95% CI): 0.35 to 2.28, I 2 = 98%, P = 0.008] and the ratio of TNF-α immunoreactivity in tissues [odds ratios (OR) =6.36, 95% CI: 1.92 to 21.05, I 2 = 66%， P = 0.002] in thyroid carcinoma are significantly higher than those in control. The serum interleukin-6 (IL-6) in patients with thyroid carcinoma is higher than that in control (SMD = 1.04, 95% CI: 0.40 to 1.67, I 2 = 96%, P = 0.001). There is no significant difference of the ratio of IL-6 immunoreactivity in tissues between carcinoma and control (OR = 1.23, 95% CI: 0.62 to 2.43, I 2 = 86%, P = 0.55). The ratio of leptin immunoreactivity in tissues is significantly associated with the risk of thyroid carcinoma (OR = 12.21, 95% CI: 3.36 to 44.40, I 2 = 85%, P < 0.00001). However, after analyzing the expression level of serum adiponectin in three studies, no significant difference is found between thyroid carcinoma and the control ( P = 0.81). Conclusions: Adipokines ( TNF-α, IL-6 and leptin ) show a strong relationship between elevated concentrations (in serum and/or tissue) and thyroid carcinoma. However, the association between adiponectin and thyroid carcinoma needs further research.
Validation of a point-of-care capillary lactate measuring device (Lactate Pro 2).
Authors: Raa Anette , Sunde Geir Arne , Bolann Bjørn , Kvåle Reidar , Bjerkvig Christopher , Eliassen Håkon Skogrand , Wentzel-Larsen Tore , Heltne Jon-Kenneth
Published: July 2020

Background: The measurement of lactate in emergency medical services has the potential for earlier detection of shock and can be performed with a point-of-care handheld device. Validation of a point-of-care handheld device is required for prehospital implementation. Aim: The primary aim was to validate the accuracy of Lactate Pro 2 in healthy volunteers and in haemodynamically compromised intensive care patients. The secondary aim was to evaluate which sample site, fingertip or earlobe, is most accurate compared to arterial lactate. Methods: Arterial, venous and capillary blood samples from fingertips and earlobes were collected from intensive care patients and healthy volunteers. Arterial and venous blood lactate samples were analysed on a stationary hospital blood gas analyser (ABL800 Flex) as the reference device and compared to the Lactate Pro 2. We used the Bland-Altman method to calculate the limits of agreement and used mixed effect models to compare instruments and sample sites. A total of 49 intensive care patients with elevated lactate and 11 healthy volunteers with elevated lactate were included. Results: There was no significant difference in measured lactate between Lactate Pro 2 and the reference method using arterial blood in either the healthy volunteers or the intensive care patients. Capillary lactate measurement in the fingertip and earlobe of intensive care patients was 47% (95% CI (29% to 68%), p<0.001) and 27% (95% CI (11% to 45%), p<0.001) higher, respectively, than the corresponding arterial blood lactate. In the healthy volunteers, we found that capillary blood lactate in the fingertip was 14% higher than arterial blood lactate (95% CI (4% to 24%), p= 0.003) and no significant difference between capillary blood lactate in the earlobe and arterial blood lactate. Conclusion: Our results showed that the handheld Lactate Pro 2 had good agreement with the reference method using arterial blood in both intensive care patients and healthy volunteers. However, we found that the agreement was poorer using venous blood in both groups. Furthermore, the earlobe may be a better sample site than the fingertip in intensive care patients.
The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations
Authors: Lin Li , Wang Ying , Sun Bijun , Liu Luyao , Ying Wenjing , Wang Wenjie , Zhou Qinhua , Hou Jia , Yao Haili , Hu Liyuan , Sun Jinqiao , Wang Xiaochuan
Published: July 2020

Background: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.Methods: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.Results: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.
Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue.
Authors: Jara Claudia , Oyarzun-Ampuero Felipe , Carrión Flavio , González-Echeverría Esteban , Cappelli Claudio , Caviedes Pablo
Published: July 2020

Background: In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients is still a challenge. For these reasons, it is necessary to explore new cellular sources and immunological isolation methods oriented to develop T1DM cell-based therapies. Aims: We postulate human adipose-derived stem cell (hASC) as an adequate source to generate pancreatic islet cells in vitro, and to produce islet-like structures. Furthermore, we propose microencapsulation of these aggregates as an immunological isolation strategy. Methods: hASC obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells. Then, insulin producing cells (IPC) and glucagon producing cells (GPC) were later cocultured in low adhesion conditions to form cellular aggregates, and later encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed. Results: The results show that multipotent hASC efficiently differentiate to IPC and GPC, and express pancreatic markers, including insulin or glucagon hormones which they secrete upon stimulation (5 fold for insulin in IPC, and 4 fold for glucagon, compared to undifferentiated cells. In turn, calculation of the Feret diameter and area of cellular aggregates revealed, finding mean diameters ~80 µm and 65 % of the aggregates reached 4000 µm2 at 72h of formation. IPC/G PC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable when stabilized with Ba2+, yielding average diameters ~300 µm. Interestingly, Ba2+-microencapsulated aggregates respond to high external glucose with insulin secretion. Conclusions: The IPC/GPC differentiation process from hASC, followed by the generation of cellular aggregates that are later microencapsulated, could represent a possible treatment for T1DM.
Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults
Authors: Lee Hyewon , Kim Kiwon , Lee Yeong Chan , Kim Soyeon , Won Hong-Hee , Yu Tae Yang , Lee Eun-Mi , Kang Jae Myeong , Lewis Matthew , Kim Doh Kwan , Myung Woojae
Published: July 2020

Background: The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age: ≥65 years). Methods: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP] and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. Results: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C, TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors.Conclusions: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.
Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway
Authors: Xue D , Sun JL , Yang J
Published: July 2020

Background: It is unclear whether the offspring of SCH pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism. Methods: Eighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16, E18, P5 (postnatal day 5 rats), and P10 (postnatal day 10 rats) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2-5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats. Results: Compared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na+/K+-ATPase and Ca2+-ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2-5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats. Conclusions: Early L-T4 intervention can regulate the cardiac development of the offspring of SCH pregnant rats by activating BMP4/Smad4 signaling pathway and increasing the expression of Gata4 and Nkx2-5 proteins.
Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.
Authors: Kenney Toby , Gao Junqiu , Gu Hong
Published: July 2020

Background: The vast majority of microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. A few models have been developed by extending time series models to accomodate specific features in microbiome data to address questions of stability and interactions of the microbime time series. Most research has observed the stability and mean reversion for some microbiomes. However, little has been done to study the mean reversion rates of these stable microbes and how sampling frequencies are related to such conclusions. In this paper, we begin to rectify this situation. We analyse two widely studied microbial time series data sets on four healthy individuals. We choose to study healthy individuals because we are interested in the baseline temporal dynamics of the microbiome. Results: For this analysis, we focus on the temporal dynamics of individual genera, absorbing all interactions in a stochastic term. We use a simple stochastic differential equation models to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for almost every genus better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics. Conclusions: There is evidence of temporal continuity for most genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8–3.2 days.
Time-restricted feeding reduces the detrimental effects of a high-fat diet, possibly by modulating the circadian rhythm of hepatic lipid metabolism and gut microbiota
Authors: Ye Yuqian , Xu Haopeng , Xie Zhibo , Wang Lun , Sun Yuning , Yang Huayu , Hu Dandan , Mao Yilei
Published: July 2020

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism. Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints. Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p<0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p<0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes. Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.
Assessment of Regional Left Ventricular Myocardial Strain in Patients with Left Anterior Descending Coronary Stenosis Using Computed Tomography Feature Tracking
Authors: Han Xiaoyu , Cao Yukun , Ju Zhiguo , Lu Jia , Li Na , Li Yumin , Liu Tong , Shi Heshui , Gu Jin
Published: July 2020

Background: Computed tomography feature tracking (CT-FT) has emerged as a valuable method for the assessment of cardiac function. However, no studies have investigated the usefulness of CT-derived assessments of left ventricular (LV) strain in coronary artery disease (CAD). Our aim was to evaluate regional LV systolic deformation in patients with left anterior descending coronary artery (LAD) stenosis using CT-FT.Methods: Seventy-six patients with LAD stenosis were enrolled. The patients were divided into four groups according to the percentage of LAD stenosis: ≤25% was defined as group I (24 patients), 26% to 49% as group II (17 patients), 50% to 74% as group III (21 patients), and ≥75% as group IV (14 patients). Thirty-two sex- and age-matched healthy subjects were included as controls.Results: No intergroup differences were found between groups I-IV and the controls in terms of the left ventricular ejection fraction, end-diastolic volume and end-systolic volume. However, the longitudinal strain (LS) of the LAD territory was significantly reduced in groups I-IV compared with the controls (-20.8%, -18.6%, -18.6%, and -17.0% vs -23.7%, respectively). The circumferential strain (CS) of the LAD territory was significantly reduced in groups III and IV compared with the controls and groups I and II (-22.4% and -22.1% vs -25.4%, -24.1%, and -25.3%, respectively). Compared with the non-LAD territory, the LAD territory in groups II-IV showed significantly increased LS (-18.6% vs -21.9%, p=0.07; -18.6% vs -21.9%, p=0.024; -17.5% vs -20%, p=0.032, respectively). The severity of LAD stenosis was positively correlated with the LS of the LAD territory (r = 0.438, p=0.002).Conclusion: CT‑FT can detect decreasing LV systolic function in patients with LAD stenosis. LV regional systolic deformation of the LAD territory was reduced with increasing LAD stenosis severity.
Prevalence of middle mesial canal and radix entomolaris of mandibular first permanent molars in a western Chinese population: an in vivo cone-beam computed tomographic study
Authors: Qiao Xin , Zhu Hualing , Yan Yujia , Li Jinglin , Ren Jiayin , Gao Yuan , Zou Ling
Published: July 2020

Background: The aim of this study was to investigate the prevalence of the middle mesial canal (MMC) and radix entomolaris (RE) in mandibular first permanent molars in a western Chinese population using cone-beam computed tomography (CBCT). Methods: A total of 1174 CBCT images of the mandibular first molars were collected from West China Hospital of Stomatology, Sichuan University. The following information was recorded and evaluated: the detection rate and location of the MMC and RE, the curvature of the RE, the canal configuration and bilateral symmetry. Results: The detection rates of the MMC and RE were 3.41% and 25.04%, respectively, as calculated by individuals, and 1.79% and 22.15%, respectively, as calculated by total teeth. The average curvature in the buccolingual (BL) orientation ( 40.63±14.3 9°) was significantly larger than that in the mesiodistal (MD)orientation ( 17.64±7.8 2°) (p<0.05). Of 587 patients, 71.72% (421/587) had bilateral symmetry according to the root canal morphology. The incidence of three-rooted mandibular first molars was higher in males than in females, while the incidence of two-rooted mandibular first molars was higher in females than in males. Conclusions: Our results showed that the RE could be detected in almost 1/4 of the western Chinese population; thus, RE detection requires special attention and careful assessment in endodontic treatment.
Knowledge, Attitude and Practice of Emergency Contraceptive Pills among Community Pharmacy Practitioners working in Kathmandu Valley: A cross-sectional study
Authors: Shakya Sujyoti , shrestha sweta , Shrestha Rojeena Koju , Giri Usha , Shrestha Sunil
Published: July 2020

Background Unintended pregnancy occurs due to incorrect or inconsistent use of a contraception method. Such pregnancies can create an economic burden on the family, society and nation as a whole. Unintended pregnancy is the underlying cause of abortion which can also result in infertility and maternal death. Adequate knowledge of emergency contraceptive pills (ECPs) and positive attitudes among the community pharmacy practitioners (CPPs) is a prerequisite for timely access of ECP, thus ultimately lessening the incidence of unintended pregnancies. This study intended to explore the knowledge, attitude and practice of CPPs toward ECPs in Kathmandu valley. Methods Cross-sectional study conducted in community pharmacies located in three districts of Kathmandu valley. A convenience sampling method was employed to interview CPPs in 227 community pharmacies using a validated questionnaire. Questionnaire assessed the demographic characteristics; knowledge, attitude and dispensing practice of the CPPs. Data were subjected to descriptive and inferential analysis using SPSS 18 (SPSS Inc., Chicago, IL, USA). Results Approximately 74.9% of respondents had a good practice on dispensing ECPs, and 70% of them counselled all the users. A significant association (p-value<0.05) was obtained between the dispensing practice of respondents and their knowledge level. ECP related knowledge was higher among the age group 40-49 years, BPharm degree holders with experience above ten years and community pharmacies located inside the city and in the Kathmandu district. After adjusting the possible confounder variables, age, degree and district of pharmacy were significantly associated with knowledge. Similarly, respondents' practice towards ECP was higher among the age group 40-49 years with experience above ten years and community pharmacies located inside the city and in the Kathmandu district. Adjusted for other variables, only community pharmacies located at Kathmandu district was significantly associated with the practice. Conclusion CPPs lacked specific important information on ECP and opined against its' availability as an OTC drug, despite good overall knowledge and positive attitude. Many thought that ECP without prescription would increase promiscuity towards sexual behaviour and result in unsafe sex along with its' repeated use. Hence, training and proper counselling strategies should be afoot to refine the delivery of service by CPPs.
Differential diagnosis for suspected cases of coronavirus disease 2019: a retrospective study
Authors: Chi Qiong , Dai Xinjian , Jiang Xiangao , Zhu Lefei , Du Junyan , Chen Yuxi , Zheng Jiyang , Huang Jianping
Published: July 2020

Background: Since December 2019, the coronavirus disease 2019 (COVID-19) has infected more than 12,310322,000 people and killed over 556,000 people worldwide. However, Differential diagnosis remains difficult for suspected cases of COVID-19 and need to be improved to reduce misdiagnosis.Methods: Sixty-eight cases of suspected COVID-19 treated in Wenzhou Central Hospital from January 21 to February 20, 2020 were divided into confirmed and COVID-19-negative groups based on the results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) nucleic acid testing of the novel coronavirus in throat swab specimens to compare the clinical symptoms and laboratory and imaging results between the groups.Results: Among suspected patients, 17 were confirmed to COVID-19-positive group and 51 were distinguished to COVID-19-negative group. Patients with reduced white blood cell (WBC) count were more common in the COVID-19-positive group than in the COVID-19-negative group (29.4% vs 3.9%, P = 0.003). Subsequently, correlation analysis indicated that there was a significant inverse correlation existed between WBC count and temperature in the COVID-19-positive patients (r=-0.587, P=0.003), instead of the COVID-19-negative group. But reduced lymphocyte count was no different between the two groups (47.1% vs 25.5%, P= 0.096). More common chest imaging characteristics of the confirmed COVID-19 cases by high-resolution computed tomography (HRCT) included ground-glass opacities (GGOs), multiple patchy shadows, and consolidation with bilateral involvement than COVID-19-negative group (82.4% vs 31.4%, P=0.0002; 41.2% vs 17.6% vs P=0.048; 76.5% vs 43.1%, P=0.017; respectively). The rate of clustered infection was higher in COVID-19-positive group than COVID-19-negative group (64.7% vs 7.8%, P=0.001). Through multiplex PCR nucleic acid testing, 2 cases of influenza A, 3 cases of influenza B, 2 cases of adenovirus, 2 cases of Chlamydia pneumonia, and 7 cases of Mycoplasma pneumoniae were diagnosed in the COVID-19-negative group.Conclusions: WBC count inversely correlated with the severity of fever, GGOs, multiple patchy shadows, and consolidation in chest HRCT and clustered infection are common but not specific features in the confirmed COVID-19 group.Reduced WBC count inversely correlating with the severity of fever, GGOs, multiple patchy shadows, and consolidation in chest HRCT and clustered infection are features in the confirmed COVID-19 group but not unique. Multiplex PCR nucleic acid testing helped differential diagnosis for suspected COVID-19 casesexclude pathogenic diagnosis in COVID-19 patients.