bluuebunny/crossref_metadata_2025 huggingface dataset:
Reno-protective effects of oral alkalizing agents in chronic kidney disease with aciduria: protocol for a randomized cohort study
Authors:   CKOALA study group, Abe Michiaki , Akaishi Tetsuya , Shoji Mutsumi , Yamaguchi Takuhiro , Miki Takashi , Satoh Fumitoshi , Takayama Shin , Yamasaki Satomi , Kawaguchi Kazuhiko , Sato Hiroshi , Ishii Tadashi , Ito Sadayoshi
Published: April 2020

Background

Aciduria caused by urinary excretion of acidic metabolic wastes produced in daily life is known to be augmented in patients with chronic kidney disease (CKD). To evaluate the reno-protective effect of oral alkalizing agents for the improvement of metabolic acidosis and neutralization of intratubular pH in the patients with mild stages of CKD. Also, to identify reno-protective surrogate markers in the serum and urine that can closely associate the effect of urine alkalization.

Methods

In this single-centered, open-labeled, randomized cohort study, patients with CKD stages G2, G3a and G3b, who visited and were treated at Tohoku University Hospital during the enrollment period were registered. We administered sodium bicarbonate or sodium-potassium citrate as the oral alkalinizing agents. A total of 150 patients with CKD will be randomly allocated into the following three groups: sodium bicarbonate, sodium-potassium citrate and standard therapy group without any alkalinizing agents. The data of performance status, venous blood test, spot urine test, venous blood-gas test, electrocardiogram, renal arterial ultrasonography and chest X-ray will be collected at 0, 6, 12 and 24 weeks (short-term study) from starting the interventions. These data will be also collected at 1 and 2 years (long-term study). The samples of plasma and serum and early-morning urine at every visit will be acquired for the analysis of renal function and surrogate uremic biomarkers.

The recruitment for this cohort study terminated in March, 2018, and the follow-up period for all the enrolled subjects will be terminated in December, 2020. The primary endpoint will be the development of originally-defined significant renal dysfunction or the occurrence of any cerebrovascular disease in the short-term study. The secondary endpoint will be the same endpoints as in the long-term study, or the patients with significant changes in the suggested the surrogate biomarkers.

Discussion

The findings of this study will address the importance of taking oral alkalizing agents in the patients with early stages of CKD, furthermore they could address any new surrogate biomarkers that can be useful from early stage CKD.

Trial registration

Registered Report Identifier: UMIN000010059 and jRCT021180043.

The trial registration number; 150.

Date of registration; 2013/02/26.
Assessment of asymptomatic bacteriuria and sterile pyuria among antenatal attendants in hospitals in northern Ghana
Authors: Karikari Akosua Bonsu , Saba Courage Kosi Setsoafia , Yamik David Yembilla
Published: April 2020

Background

Asymptomatic bacteriuria (ASB) and sterile pyuria (SP) are complexities of UTI whose prevalence are not known in the northern sector of Ghana. Our aim was to determine the occurrence of sterile pyuria and asymptomatic bacteriuria among pregnant women accessing antenatal care at a secondary and tertiary care hospitals in Tamale, northern Ghana.

Methods

A cross sectional study was conducted by screening 530 pregnant women with no signs of acute urinary tract infection attending antenatal clinic for a period of 6 months. Midstream urine was collected for microscopy, quantitative urine culture and antibiotic susceptibility testing. Data analysis was carried out using the Statistical Package for Social Sciences version 20.

Results

Asymptomatic bacteriuria was respectively 20 and 35.5% at Tamale Central and Tamale Teaching Hospital out of the 390 and 90 women screened. Sterile pyuria was found among 66% of the 50 women presenting at Tamale Central Hospital. More than 64% of isolates recovered from ASB patients wereS. aureusandcoagulase negative Staph.(CoNS).Escherichia coliwas the dominant species among members of the enterobacteriaceae isolated. Highest susceptibility was recorded against gentamicin and amikacin while most resistance was to Ampicillin, cotrimoxazole, chloramphenicol and nitrofurantoin. Resistance to imipenem and vancomycin were 28.8 and 52%, with strains showing multiple drug resistance of between 81 and 92%.

Conclusion

The prevalence of asymptomatic bacteriuria is appreciably higher (20–35.5%) than documented rates in the southern sector of the country. The presence of sterile pyuria which may be an indication of asymptomatic renal impairment and most often overlooked in antenatal management is 66%. Empirical treatment of UTIs at the Tamale Central and Teaching Hospital without confirmation of susceptibility may result in treatment failure. It is necessary to screen and treat pregnant women for ASB and SP due to the complications associated with these conditions.
Plasmacytoma in patients with multiple myeloma: morphology and immunohistochemistry
Authors: Firsova Maiia V. , Mendeleeva Larisa P. , Kovrigina Alla M. , Solovev Maxim V. , Savchenko Valery G.
Published: April 2020

Background

To study the histological structure and immunohistochemical (IHC) parameters of the plasmacytoma tumour substrate in patients with multiple myeloma (MM).

Methods

The study included 21 patients (10 men/11 women) aged 23 to 73 years old with newly diagnosed MM complicated by plasmacytoma. Bone plasmacytoma was diagnosed in 14 patients, and extramedullary plasmacytoma was diagnosed in 7 patients. Plasmacytoma tissue specimens were examined using a LEICA DM4000B microscope. Anti-CD56, anti-CD166, anti-CXCR4, anti-Ki-67, and anti-c-MYC antibodies were used for IHC study of plasmacytoma biopsies.

Results

When comparing the morphology of bone and extramedullary plasmacytoma, no significant differences were revealed; however, the substrate of extramedullary plasmacytoma was more often represented by tumour cells with an immature morphology than was the bone plasmacytoma substrate (57.1% vs. 28.6%, respectively). We revealed a significant difference in the expression of CD166 between bone and extramedullary plasmacytoma. The mean values ​​of CD166 expression in bone plasmacytoma cells were significantly higher (36.29 ± 7.61% versus 9.57 ± 8.46%, respectively; p = 0.033) than those in extramedullary plasmacytoma cells. We noticed that in extramedullary plasmacytoma cells, there were higher values for the Ki-67 index than in bone plasmacytoma cells, and this result was independent of cell morphology.

Conclusion

The mechanisms involved in the dissemination of tumour plasma cells are currently unexplored. Even in such a small sample, some differences in expression could be identified, which may indicate that different mechanisms lead to the formation of bone and extramedullary plasmacytomas. Specifically, the expression of CD166 in extramedullary plasmacytoma cells was almost 4 times lower than that in bone plasmacytoma cells, which may indicate the involvement of CD166 in the mechanisms of bone destruction. The proliferative activity of extramedullary plasmacytoma cells was shown to be higher than that of bone plasmacytoma cells.
Communication of children’s weight status: what is effective and what are the children’s and parents’ experiences and preferences? A mixed methods systematic review
Authors: Ames H. , Mosdøl A. , Blaasvær N. , Nøkleby H. , Berg R. C. , Langøien L. J.
Published: April 2020

Background

Early intervention and conversation about a child’s weight may offer an important chance of success in reducing weight and implementing a healthier lifestyle. This review explores the most effective ways to notify parents and children about the child’s weight as well as their preferences and experiences around weight notification.

Methods

We systematically searched nine databases for relevant primary research. Records were independently screened by two authors. We extracted data into a form designed for this review. Effect data was analysed using narrative synthesis and qualitative data using a best-fit framework synthesis. We assessed our confidence in the evidence using GRADE and GRADE-CERQual.

Results

Studies of effect found that the format of feedback made little or no difference in parents attending further treatment, recognising their child as overweight or obese, reactions to the way the weight notification is given, motivation for lifestyle change, understanding how to reduce the risk of overweight, or taking any action. However, parents receiving feedback with motivational interviewing have somewhat greater satisfaction with the way the healthcare provider supports them.

Qualitative studies found that parents had clear preferences for the format, timing, content and amount of information they wanted to receive in relation to both the weighing process and weight notification. They also had clear preferences for how they wanted health care providers to interact and communicate with them and their children. Both parents and children often felt that they were not receiving enough information and worried about how their results would be kept private. Many parents experienced an emotional response when told about their child’s weight ranging from positive, disbelief and negative feelings. Those who reacted with disbelief or negatively were less likely to accept their child’s weight status and/or act upon the notification letter.

No studies reported results for children who were underweight.

Conclusions

Based on these qualitative results people working with weight assessment and notification programs should consider parents’ preferences when developing feedback formats, considering the mode of feedback they are going to use and provide parents and children with tailored feedback and personalized follow up once a child is identified as overweight or obese.
The role of trust and health literacy in nurse-delivered point-of-care STI testing for pregnant women living with HIV, Tshwane District, South Africa
Authors: Medina-Marino Andrew , Glockner Katherine , Grew Emily , De Vos Lindsey , Olivier Dawie , Klausner Jeffrey , Daniels Joseph
Published: April 2020

Background

Sexually transmitted infections (STIs) during pregnancy result in neonatal morbidity and mortality, and may increase mother-to-child-transmission of HIV. Yet the World Health Organization’s current syndromic management guidelines for STIs leaves most pregnant women undiagnosed and untreated. Point-of-care (POC) diagnostic tests for STIs can drastically improve detection and treatment. Though acceptable and feasible, poor medication adherence and re-infection due to lack of partner treatment threaten the programmatic effectiveness of POC diagnostic programmes.

Methods

To engender patient-provider trust, and improve medication adherence and disclosure of STI status to sexual partners, we trained study nurses in compassionate care, good clinical practices and motivational interviewing. Using qualitative methods, we explored the role patient-provider communications may play in supporting treatment adherence and STI disclosure to sexual partners. Nurses were provided training in motivational interviewing, compassionate care and good clinical practices. Participants were interviewed using a semi-structured protocol, with domains including STI testing experience, patient-provider communication, and HIV and STI disclosure. Interviews were audio-recorded, transcribed and analyzed using a constant comparison approach.

Results

Twenty-eight participants treated for Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), and/or Neisseria gonorrhea (NG) were interviewed. Participants described strong communications and trusting relationships with nurses trained in patient-centered care training and implementing POC STI diagnostic testing. However, women described a delayed trust in treatment until their symptoms resolved. Women expressed a limited recall of their exact diagnosis, which impacted their ability to fully disclose their STI status to sexual partners.

Conclusions

We recommend implementing patient health literacy programmes as part of POC services to support women in remembering and disclosing their specific STI diagnosis to sexual partners, which may facilitate partner treatment uptake and thus decrease the risk of re-infection.
Establishing the HLS-M-Q18 short version of the European health literacy survey questionnaire for the Malaysian context
Authors: Mohamad Emma Mirza Wati , Kaundan Manimaran Krishnan , Hamzah Mohammad Rezal , Azlan Arina Anis , Ayub Suffian Hadi , Tham Jen Sern , Ahmad Abdul Latiff
Published: April 2020

Background

The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is becoming a widely used tool to measure health literacy (HL), including in Malaysia. There are efforts to reduce the 47-item scale to parsimonious short item scales that still reflect the assumptions and requirements of the conceptual model. This study used confirmatory factor analysis to reduce the 47-item scale to a short scale that can offer a feasible HL screening tool with sufficient psychometric properties.

Methods

A cross-sectional survey was conducted on the Malaysian population based on ethnic distribution to ensure that the short version instrument reflects the country’s varied ethnicities. The survey was administered by well-trained interviewers working for the Ministry of Health Malaysia. A total of 866 responses were obtained. Data was analysed using multi-factorial confirmatory factor analysis (CFA) with categorical variables.

Results

The analysis resulted in a satisfactory 18-item model. There were high correlations among the 18 items. The internal consistency reliability was robust, with no floor/ceiling effects. These results represented equivalence and consistency among the responses to items, suggesting that these items were homogenous in measuring Malaysian health literacy. The strong convergent and discriminant validity of the model makes the proposed 18 items a suitable short version of the health literacy instrument for Malaysia.

Conclusions

The researchers propose the 18-item instrument to be named HLS-M-Q18. This short version instrument may be used in measuring health literacy in Malaysia as it achieved robust reliability, structural validity and construct validity that fulfilled goodness-of-fit criteria.
The changing relationship between health burden and work disability of Australian cancer survivors, 2003–2017: evidence from a longitudinal survey
Authors: Mahumud Rashidul Alam , Alam Khorshed , Dunn Jeff , Gow Jeff
Published: April 2020

Background

The purpose of this study was to examine the relationship between the cancer health burden and themagnitude of work disability on cancer survivors in Australia from 2003 to 2017.

Methods

A longitudinal prospective study design was undertaken among cancer patients using data from the Household, Income and Labour Dynamics in Australia survey. The longitudinal effect was captured using a fixed effect multinomial logistic regression model, which predicted changes in the relationship between cancer burden and work disability level controlling for socio-demographic, lifestyle and life conditions predictors.

Results

The prevalence of long-term disability among cancer survivors was 50%, with 18% of patients experiencing extreme work disability. The magnitude of disability levels increased significantly with the level of health burden. Cancer survivors who faced a severe health burden were at 5.32 times significantly higher risk of having work disability compared with patients who had no health burden. Other potential predictors, such as older patients (relative risk ratio, RRR = 1.82; 95% CI: 1.57, 5.87), those engaged in lower levels of physical activities (RRR = 1.91; 95% CI: 1.07, 3.40), those who drink alcohol (RRR = 1.29; 95% CI: 1.15, 1.49), and poor socioeconomic status (RRR = 1.28; 95% CI: 1.16, 2.23) were all significantly associated with extreme work disability.

Conclusion

A substantial proportion of cancer survivors experienced work disability which was more pronounced with the magnitude of the cancer health burden. The different dimensions of disability might be prevented by introducing cancer survivor-specific evidence-based interventions, and incorporating comprehensive social support. Recommendations to improve public health policy aimed at reducing population-level unhealthy lifestyle behaviours include: using these findings to better outline the management of a sequelae course of treatment for cancer survivors; and identifying those who should undergo more intensive physical rehabilitation aimed at reducing their work disability level.
Effect and potential risks of using multilevel cement-augmented pedicle screw fixation in osteoporotic spine with lumbar degenerative disease
Authors: Tang Yong-chao , Guo Hui-zhi , Guo Dan-qing , Luo Pei-jie , Li Yong-xian , Mo Guo-ye , Ma Yan-huai , Peng Jian-cheng , Liang De , Zhang Shun-cong
Published: April 2020

Background

The increase of augmented level and bone cement dose are accompanied by the rising incidence of cement leakage (CL) of cement-augmented pedicle screw instrumentation (CAPSI). But the effect and potential risks of the application of CAPSI to osteoporotic lumbar degenerative disease (LDD) have not been studied in the case of multilevel fixation. This study aimed to investigate the effectiveness and potential complications of using multilevel CAPSI for patients with osteoporotic LDD.

Methods

A total of 93 patients with multilevel LDD were divided into the CAPSI group (46 subjects) and the conventional pedicle screw (CPS) group (47 subjects), including 75 cases for three levels and 18 cases for four levels. Relevant data were compared between two groups, including baseline data, clinical results, and complications.

Results

In the CAPSI group, a total of 336 augmented screws was placed bilaterally. The CL was observed in 116 screws (34.52%). Three cemented screws (0.89%) were found loosened during the follow-up and the overall fusion rate was 93.47%. For perioperative complications, two patients (4.35%) experienced pulmonary cement embolism (PCE), one patient augmented vertebral fracture, and three patients (6.52%) wound infection. And in the CPS group, thirty-three screws (8.46%) suffered loosening in cranial and caudal vertebra with a fusion rate of 91.49%. The operation time and hospital stay of CAPSI group were longer than the CPS group, but CAPSI group has a lower screw loosening percentage (P<0. 05). And in terms of blood loss, perioperative complications, fusion rate, and VAS and ODI scores at the follow-up times, there were no significant differences between the two groups.

Conclusions

Patients with osteoporotic LDD underwent multilevel CPS fixation have a higher rate of screw loosening in the cranial and caudal vertebra. The application of cemented pedicle screws for multilevel LDD can achieve better stability and less screw loosening, but it also accompanied by longer operating time, higher incidence of CL, PCE and wound infections. Selective cement augmentation of cranial and caudal pedicle screws may be a worthy strategy to decrease the complications.
Modern contraceptive use among postpartum women living with HIV attending mother baby care points in Kabarole District, Uganda
Authors: Tusubira Andrew K. , Kibira Simon Peter Sebina , Makumbi Fredrick Edward
Published: April 2020

Background

Preventing unintended pregnancies among women living with HIV is important for improving maternal and child health outcomes. Despite multiple contacts between postpartum women and healthcare providers at health facilities, modern contraceptive use during postpartum period remains low even among women with intentions to limit or delay childbearing. We estimated postpartum modern contraceptive use, unmet need and factors associated with modern contraceptive use among HIV positive women attending mother-baby HIV care points.

Methods

We conducted a cross-sectional study, between April and May 2016, among HIV positive women attending postpartum care at six health facilities in Kabarole district, Uganda. Health facilities were stratified by level prior to selecting participants using systematic sampling. We administered structured questionnaires to women who had delivered within the last two to 18 months. Women who reported current use of a modern method were categorized as modern contraceptive users. Women not using but wanted to stop childbearing or space childbirth by at least 2 years were considered to have unmet need for modern contraception. We estimated a modified Poisson regression model to examine variations in the use of modern methods by various characteristics of participants.

Results

We interviewed 369 women. Forty percent of them were using a modern method, with injectables being the most widely used. A third (33%) of the women had unmet need for modern methods, with unmet need for spacing (24%) being higher than for limiting births (9%). Modern contraceptive use was significantly higher among women who had delivered seven or more months earlier (Adj.PR = 2.02; CI: 1.49, 2.74); women who were counseled on family planning during antenatal care (Adj.PR = 1.53; CI: 1.07, 2.18); those who obtained methods through the care points (Adj.PR =2.27; CI: 1.32, 3.90); and those who jointly made decisions regarding childbearing with their partners (Adj.PR = 1.49; CI: 1.02, 2.17).

Conclusion

Use of modern contraceptives was low while unmet need was high among postpartum women living with HIV. The findings suggest that there are gaps which indicate the need to strengthen contraceptive service delivery at these care-points. Providing family planning counseling early would improve uptake of contraception upon resumption of menses and sexual activity.
Prevalence, knowledge, attitude and practices of female genital mutilation and cutting (FGM/C) among United Arab Emirates population
Authors: Al Awar Shamsa , Al-Jefout Moamar , Osman Nawal , Balayah Zuhur , Al Kindi Nourah , Ucenic Teodora
Published: April 2020

Background

Female genital mutilation/cutting (FGM/C) is a common practice in developing countries, including the UAE, and presents a major health problem.

Methods

A questionnaire-based cross-sectional study was conducted among 1035 participants: 831 (80.3%) females and 204 (19.7%) males.

Results

The number of women with FGM/C was 344; hence the prevalence of FGM/C in our study was 41.4%. Type I was the most prevalent (62.8%), followed by Type II (16.6%) and Type III (5%). FGM/C was less prevalent among educated and employed women (p-value < 0.001) and was mostly performed during infancy and childhood. Among the participants, 13.7% reported that their daughters had undergone FGM/C, with Type I being the most common, and 25% of them planned to have their future daughters undergo Type I FGM/C. While FGM/C was mostly performed by ritual circumcisers (74.4%), in 25 and 36.7% of the cases, it was performed by health professionals and in the clinic setting, respectively. About 69% of the participants considered FGM/C a custom, 72.8% were against the practice, and only 17.4% believed in its legality. Complications occurred in 30% of cases. The type of FGM/C was associated with the occurrence of complications: bleeding, difficulties in sexual life, and delivery-related problems (p-value < 0.05). One-fifth of the male participants expressed plans to circumcise future daughters (p-value < 0.001).

Conclusion

FGM/C remains a prevalent practice in the UAE and has a negative association with the general health of Emirati women. The lack of clear legislation to criminalize this practice is a problem to be addressed. In this context, national-level educational and legal strategies should be a priority.
Effects of stigma, hope and social support on quality of life among Chinese patients diagnosed with oral cancer: a cross-sectional study
Authors: Zhang Ying , Cui Chunying , Wang Yu , Wang Lie
Published: April 2020

Background

Improving quality of life (QoL) has been one of the goals of health care for people living with oral cancer. This study aimed to assess QoL and investigate the effects of stigma, hope, and social support on QoL among Chinese oral cancer patients.

Methods

A cross-sectional study was conducted at the Department of Stomatology, Shengjing Hospital of China Medical University and Stomatology Hospital of China Medical University in Liaoning Province, China, between May 2016 and October 2017. A total of 230 oral cancer patients were recruited to complete a questionnaire including the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), the Social Impact Scale (SIS), the Herth Hope Index (HHI) and the Multidimensional Scale of Perceived Social Support (MSPSS). Univariate one-way ANOVA/t-test, Person’s r and hierarchical linear regression analysis were conducted to explore the factors influencing QoL and the relationships between stigma, hope, perceived social support and QoL.

Results

The mean QoL score was 90.85 ± 20.15 among the patients with oral cancer. Stigma was negatively related to QoL, explaining 39.3% of the variance. In addition, hope and perceived social support were positively associated with QoL, explaining 8.1% of the variance.

Conclusion

Overall, Chinese patients with oral cancer suffer from low QoL. Stigma was significantly and negatively associated with QoL, while hope and perceived social support were positively associated with QoL. Oral cancer patients’ psychological states should be addressed, and adequate intervention based on positive psychological resources should be provided to improve the QoL of patients with oral cancer.
Colon metal stents as a bridge to surgery had no significant effects on the perineural invasion: a retrospective study
Authors: Cao Yinghao , Yang Ming , Yan Lizhao , Deng Shenghe , Gu Junnan , Mao Fuwei , Wu Ke , Liu Li , Cai Kailin
Published: April 2020

Purpose

The long-term oncological effects of self-expandable metallic stent (SEMS) as a “bridge to surgery” are contradictory, and perineural invasion was supposed to be enhanced by the stenting. In this retrospective study, we compared the perineural invasion and the oncological outcomes between the stent as a bridge to surgery (SBTS)- and emergency surgery (ES)-treated patients to evaluate the results of stenting on the perineural invasion.

Methods

The clinical data of patients with acute intestinal obstruction caused by colorectal cancer from January 2013 to January 2017 were retrospectively collected. Forty-three patients underwent semi-elective curative resection after endoscopic SEMS insertion, and sixty-three underwent ES. The adverse events and long-term follow-up outcomes were assessed. The clinicopathological characteristics, perineural invasion rates, and survival rates were compared between the two patient groups.

Results

Stent insertion resulted in significantly lower stoma rate (32.6% vs 46%; P = 0.03), post-operative overall complication rate (11.6% vs 28.6%, P = 0.038), and total hospital stay (17.07 ± 5.544 days vs 20.48 ± 7.372 days, P = 0.042). Compared with the ES group, there was no significant increase in the incidence of peripheral invasion in the SBTS group (39.5% vs 47.6%, P = 0.411). No significant difference was noted in the survival rate and long-term prognosis between the SEMS and ES groups (P = 0.964). The technical success rate was 95.6%, and the clinical success rate was 97.7%.

Conclusions

Preoperative colon stenting was an effective transitional method for colorectal cancer patients with complete obstruction. Short-term stent implantation had no significant effect on perineural invasion in patients with CRC.
Virtual reality distraction induces hypoalgesia in patients with chronic low back pain: a randomized controlled trial
Authors: Matheve Thomas , Bogaerts Katleen , Timmermans Annick
Published: April 2020

Background

Attentional distraction from pain has been shown to be largely ineffective for obtaining a hypoalgesic effect in patients with chronic pain when compared to a control condition. It has been hypothesized that this may be due to the non-engaging types of distraction that have been used so far. Moreover, it is suggested that the hypoalgesic effects of distraction may be attenuated by pain-related cognitions and emotions, as they may increase the attention to pain.

Methods

In this randomized controlled trial, patients with chronic nonspecific low back pain in the intervention group (n = 42) performed a single exercise session with nonimmersive VR games, while those in the control group (n = 42) performed the same exercises without VR games. We investigated whether VR distraction had a hypoalgesic effect during and immediately after the exercises, and whether it reduced the time spent thinking of pain during the exercises. We further explored whether pain-related fear, pain catastrophizing and baseline pain intensity moderated the effects of VR distraction.

Results

VR distraction had a hypoalgesic effect during (Cohen’s d = 1.29) and immediately after (Cohen’s d = 0.85) the exercises, and it also reduced the time spent thinking of pain (Cohen’s d = 1.31). Preliminary exploratory analyses showed that pain-related fear, pain catastrophizing and baseline pain intensity did not moderate the effects of VR distraction.

Conclusions

Large effect sizes of VR distraction induced hypoalgesia were observed. This suggests that nonimmersive VR games can be used when it is deemed important to reduce the pain during exercises in patients with chronic nonspecific low back pain.

Trial registration

NCT02679300. This trial was registered on 10 February 2016.
Recent advances in human iPSC-derived models of the blood–brain barrier
Authors: Workman Michael J. , Svendsen Clive N.
Published: April 2020

The blood–brain barrier (BBB) is a critical component of the central nervous system that protects neurons and other cells of the brain parenchyma from potentially harmful substances found in peripheral circulation. Gaining a thorough understanding of the development and function of the human BBB has been hindered by a lack of relevant models given significant species differences and limited access to in vivo tissue. However, advances in induced pluripotent stem cell (iPSC) and organ-chip technologies now allow us to improve our knowledge of the human BBB in both health and disease. This review focuses on the recent progress in modeling the BBB in vitro using human iPSCs.
Culture-induced changes in mRNA expression levels of efflux and SLC-transporters in brain endothelial cells
Authors: Goldeman C. , Ozgür B. , Brodin B.
Published: April 2020

Background

The complexity of the neurovascular unit (NVU) poses a challenge in the investigations of drug transport across the blood–brain barrier (BBB) and the function of the brain capillary endothelium. Several in vitro models of the brain capillary endothelium have been developed. In vitro culture of primary endothelial cells has, however, been reported to alter the expression levels of various brain endothelial proteins. Only a limited number of studies have addressed this in detail. The aim of the present study was to investigate mRNA levels of selected BBB transporters and markers in in vitro models of the BBB based on bovine primary endothelial cells and compare these to the levels estimated in freshly isolated bovine brain capillaries.

Methods

Brain capillaries were isolated from bovine cerebral cortex grey matter. Capillaries were seeded in culture flasks and endothelial cells were obtained using a brief trypsinization. They were seeded onto permeable supports and cultured in mono-, non-contact- or contact co-culture with/without primary rat astrocytes. mRNA-expression levels of the selected BBB markers and transporters were evaluated using qPCR and monolayer integrity of resulting monolayers was evaluated by measuring the transendothelial electrical resistance (TEER).

Results

The capillary mRNA transcript profile indicated low expression of ABCC1 and CLDN1. The mRNA expression levels of TPA, OCLN, ABCB1, SLC2A1, SLC16A1 and SLC7A5 were significantly decreased in all culture configurations compared to freshly isolated bovine brain capillaries. ALP, VWF, ABCC1 and ABCC4 were upregulated during culture, while the mRNA expression levels of F11R, TJP1, CLDN5, CLDN1 and ABCG2 were found to be unaltered. The mRNA expression levels of VWF, ALP, ABCB1 and ABCC1 were affected by the presence of rat astrocytes.

Conclusion

The endothelial mRNA transcript profile in bovine capillaries obtained in this study correlated nicely with profiles reported in mice and humans. Cultured endothelial cells drastically downregulated the mRNA expression of the investigated SLC transporters but maintained expression of efflux transporter and junctional protein mRNA, implying that the bovine in vitro BBB models may serve well to investigate basic barrier biology and in vivo permeation of passively permeating compounds and efflux transporter substrates but may be less well suited for investigations of SLC-mediated transport.
Novel ABCB4 mutation in a Chinese female patient with progressive familial intrahepatic cholestasis type 3: a case report
Authors: Wu Zhenping , Zhang Siying , Zhang Lunli , Li Ming
Published: April 2020

Background

Progressive familial intrahepatic cholestasis (PFIC) is a rare group of autosomal recessive hereditary hepatic diseases. There are three types of PFIC, classified according to the mutated gene. For example, PFIC type 3 (PFIC3) is due to mutations in the ABCB4 gene (encoding multidrug-resistant protein 3 [MDR3]).

Case presentation

We present a 19-year-old Chinese female patient who had a 2-year history of recurrent liver dysfunction, with mainly elevated alkaline phosphatase and γ-glutamyl transpeptidase(γ-GT) levels. After excluding other causes of abnormal liver function and cholestasis, the final diagnosis of PFIC3 was confirmed by histopathological examination and gene detection. The immunohistochemical results showed no MDR3 protein expression in the bile duct membrane. Genetic sequencing analysis revealed a novel heterozygous 2137G > A; p. V713M mutation (Exon 17) and a synonymous 504C > T; p. N168N mutation (Exon 6) in ABCB4.

Conclusions

Our patient with long-term liver dysfunction demonstrated that elevated alkaline phosphatase and γ-GT levels should be associated with the diagnosis of PFIC3, and gene detection is the key to diagnosis. From our in silico analysis, the novel mutation p. V713M in Exon 17 was predicted to affect protein function, with a SIFT (Sorting Intolerant from Tolerant) score of 0.02, indicating a deleterious effect. Further studies are necessary to investigate the impact of the novel heterozygous 2137G > A; p. V713M mutation (Exon 17) on functional defects of MDR3 and PFIC3.
Breastfeeding practices in Masaya, Nicaragua: a facility based cross-sectional study
Authors: Nabower Aleisha M. , Lyden Elizabeth R. , Rodriguez Francisco J. , Delair Shirley F.
Published: April 2020

Background

The World Health Organization recommends exclusive breastfeeding for 6 months and total breastfeeding for at least 2 years. Despite this and multiple interventions promoting breastfeeding, early breastfeeding cessation remains high with little data as to the ongoing barriers contributing to early cessation.

Methods

Two groups of Nicaraguan mothers in an urban hospital were approached to complete a questionnaire to determine what newborn, maternal, and socioeconomic factors contributed to early cessation of breastfeeding. Group 1 participants were mothers of newborns in the newborn units, while group 2 were mothers of children 5 years or younger in the emergency room and pediatric ward. Descriptive statistics summarized the data. Fisher’s exact test evaluated factors associated with early breastfeeding cessation.

Results

In group 1, 97 participants were enrolled with 81% of mothers planning to fulfill the guideline for exclusive breastfeeding for 6 months. In group 2, there were 139 mothers of which 58% reported they had exclusively breastfed for 6 months. Only 25 and 27% of mothers in group 1 and 2 respectively planned to breastfeed or breastfed for 2 years. In group 1, mothers reported lack of knowledge regarding breastfeeding techniques and older mothers tended to plan for early cessation of exclusive breastfeeding. In group 2, mothers reported feeling uncomfortable with breastfeeding in public or had difficulty with latching. Cessation of any breastfeeding prior to 12 months was associated with being uncomfortable breastfeeding in public and knowing the WHO guidelines. In both groups, social media represented an expanding platform for receiving breastfeeding information.

Conclusions

Interventions focusing on reaching younger mothers and addressing breastfeeding knowledge and techniques while leveraging the increasing influence of social media platforms may help improve compliance with breastfeeding recommendations.
Development and external validation of a nomogram to predict overall survival following stereotactic body radiotherapy for early-stage lung cancer
Authors: Baker Sarah , Bakunina Katerina , Duijm Marloes , Hoogeman Mischa S. , Cornelissen Robin , Antonisse Imogeen , Praag John , Heemsbergen Wilma D. , Nuyttens Joost Jan
Published: April 2020

Background

Prognostication tools for early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) are currently lacking. The purpose of this study was to develop and externally validate a nomogram to predict overall survival in individual patients with peripheral early-stage disease.

Methods

A total of 587 NSCLC patients treated with biologically effective dose > 100 Gy10 were eligible. A Cox proportional hazards model was used to build a nomogram to predict 6-month, 1-year, 3-year and 5-year overall survival. Internal validation was performed using bootstrap sampling. External validation was performed in a separate cohort of 124 NSCLC patients with central tumors treated with SBRT. Discriminatory ability was measured by the concordance index (C-index) while predictive accuracy was assessed with calibration slope and plots.

Results

The resulting nomogram was based on six prognostic factors: age, sex, Karnofsky Performance Status, operability, Charlson Comorbidity Index, and tumor diameter. The slope of the calibration curve for nomogram-predicted versus Kaplan-Meier-estimated overall survival was 0.77. The C-index of the nomogram (corrected for optimism) was moderate at 0.64. In the external validation cohort, the model yielded a C-index of 0.62.

Conclusions

We established and validated a nomogram which can provide individual survival predictions for patients with early stage lung cancer treated with SBRT. The nomogram may assist patients and clinicians with treatment decision-making.
Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database
Authors: Welters Alena , Meissner Thomas , Konrad Katja , Freiberg Clemens , Warncke Katharina , Judmaier Sylvia , Kordonouri Olga , Wurm Michael , Papsch Matthias , Fitzke Gisela , Schmidt Silke Christina , Tittel Sascha R. , Holl Reinhard W.
Published: April 2020

Background

Wolcott-Rallison syndrome (WRS) is characterized by permanent early-onset diabetes, skeletal dysplasia and several additional features, e.g. recurrent liver failure. This is the first multicentre approach that focuses on diabetes management in WRS. We searched the German/Austrian Diabetes-Patienten-Verlaufsdokumentation (DPV) registry and studied anthropometric characteristics, diabetes treatment, glycaemic control and occurrence of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in 11 patients with WRS. Furthermore, all local treatment centres were personally contacted to retrieve additional information on genetic characteristics, migration background and rate of consanguinity.

Results

Data were analysed at diabetes onset and after a median follow-up period of 3 (1.5–9.0) years (time from diagnosis to latest follow-up). Median age at diabetes onset was 0.2 (0.1–0.3) years, while onset was delayed in one patient (aged 16 months). Seventy percent of patients manifested with DKA. At follow-up, 90% of patients were on insulin pump therapy requiring 0.7 [0.5–1.0] IU of insulin/kg/d. More than two third of patients had HbA1c level ≥ 8%, 40% experienced at least one episode of SH in the course of the disease. Three patients died at 0.6, 5 and 9 years of age, respectively. To the best of our knowledge three patients carried novel mutations in EIF2AK3.

Conclusion

Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.
Systematic screening for cervical cancer in Dakar region: prevalence and correlation with biological and socio-demographic parameters
Authors: Diouf Dominique , Diop Gora , Diarra Cheikh Ahmadou Tidian , Ngom Aminata Issa , Niane Khadija , Ndiaye Moussa , Ka Sidy , Faye Oumar , Dem Ahmadou
Published: April 2020

Background

Cervical cancer is a major public health problem. In 2018, globally 569,847 cervical cancer were diagnosed and 311,000 deaths were projected due to this preventable disease. Worldwide, therefore, the cervical cancer disease ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women in 2018.

The high rate of dysplasia in Senegal and the absence of well-organized screening programs informed this study, which aims to determine the prevalence of cervical dysplasia and its relationship to biological and socio-demographic characteristics.

Methods

This study is based on 1000 conventional smears collected during routine cervical cancer screening at the Gaspard Camara Health Center and the Histology - Embryology and Cytogenetics Laboratory of the Cheikh Anta DIOP University in Dakar. The smears were read according to the Bethesda and Richart systems. However, all data were returned to the Bethesda system using the correspondence table between the different classifications of squamous cell lesions of the cervix. Some of the patients with abnormal smears had colposcopy and if necessary a biopsy. Other patients with low-grade lesions were recommended to have their smears resumed in 6 months or 1 year later.

Results

Cytological analysis was performed for 1000 patients aged 16 to 82 years (mean age = 41 ± 11.16). Among these, 176 patients had abnormal smears, 23 had Atypical Squamous Cells of Undetermined Significance (ASCUS), 143 had a low-grade lesion, 9 had a high-grade lesion and 1 had carcinoma. Among the remaining 822 patients, cytological analysis revealed no suspected malignant lesions, but 623 among them had dystrophy and 2 were unsatisfactory. Among patients with abnormal smears, 104 patients (23 ASCUS + 71 low grade + 9 high grade + 1 carcinoma) had performed colposcopy, 40 of whom had normal colposcopy and 64 had abnormalities. Sixty-four (64) biopsies were performed. Four (4) were not satisfactory. However, for 26/60 biopsies, the histology was normal, 21/60 had a low grade, 11 displayed a high grade and only 2 had carcinoma. Among the 176 patients with abnormal smears, 72 low-grade patients had undergone cytological examination 6 months to 1 year later to determine the persistence, regression or progression of low-grade dysplasia. During follow-up, persistence was observed in 25% (n = 18) of cases, progression to High-grade squamous intraepithelial lesion (HSIL) was detected in 2.78% (n = 2), while 72.22% (n = 52) of the patients experienced regression.

Conclusion

In this study, the prevalence of abnormal smear was 17.60% for cytology. Meanwhile, the Colposcopy and histology confirmed just 3.40%. These results underline the interest and need for a review of the discrepancies observed between pathologists.
Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial
Authors: Kuon Jonas , Hommertgen Adriane , Krisam Johannes , Lasitschka Felix , Stenzinger Albrecht , Blasi Miriam , Bozorgmehr Farastuk , Maenz Martin , Kieser Meinhard , Schneider Marc , Thomas Michael
Published: April 2020

Background

Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.

Methods/design

This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or “frail” (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1).

Patients are stratified according to modified Cancer and Age Research Group (CARG) score: “fit” patients are allocated to combination CT (carboplatin/nab-paclitaxel) and “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks.

The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.

Discussion

The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.

Trial registration

ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017.

Eudra-CT, 2016–003963-20; initially registered on 3 January 2017.
Phenylethanol glycosides from the seeds of Aesculus chinensis var. chekiangensis
Authors: Zhang Nan , Liu Di , Wei Shuxiang , Cao Shijie , Feng Xinchi , Wang Kai , Ding Liqin , Qiu Feng
Published: April 2020

Three new phenylethanol glycosides (1-3) and one known analogue (4) were isolated from the seeds of Aesculus chinensis Bge. var. chekiangensis. To the best of our knowledge, this represents the first isolation of phenylethanol glycosides from the genus of Aesculus, which enriched its chemical composition. Structure elucidations were performed via extensive NMR and HRESIMS data together with comparison with literature data. Thereafter, the isolated compounds were assayed for their neuroprotective activities against CoCl2-induced cytotoxicity in PC12 cells and compound 3 exhibited moderate activity. "Image missing"