bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymicrobial infections and microbial patterns in infected nonunions – a descriptive analysis of 42 cases
Authors: Rupp Markus , Kern Stefanie , Weber Tobias , Menges Tamina D. , Schnettler Reinhard , Heiß Christian , Alt Volker
Published: September 2020

Background

Frequencies of polymicrobial infection and pathogens evidenced in course of infected nonunion treatment are largely unknown. Therefore, this study aims at investigating microbial patterns in infected nonunions.

Methods

Surgically treated patients with long bone infected nonunion admitted between January 2010 and March 2018 were included in the study. Microbiological culture and polymerase-chain-reaction results of tissue samples of initial and follow-up revision surgeries were assessed and compared with patient and treatment characteristics.

Results

Forty two patients with a mean age of 53.9 ± 17.7 years were included. In six patients (14.3%) polymicrobial infection was evident. A change of pathogens evidenced in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be determined by microbial testing after further revision surgery. Staphylococcus aureus was most often detected (n = 34, 30.6%), followed by Enterococcus spp. (n = 25, 22.5%) and Staphylococcus epidermidis (n = 18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment, 86.4% of the infections were due to Staphylococcus spp.. Infections due to Streptococcus spp. and gram-negative bacteria were only present in patients with polymicrobial infection and germ-change in course of the treatment.

Conclusion

A low rate of polymicrobial infections was evidenced in the present study. Germ-change often occurs in course of revision surgeries. Prospective studies with more sensitive diagnostic tools are necessary to elucidate the therapeutical relevance of microbiological testing results for surgical as well as medical treatment in infected nonunions.
NMDA receptor-mediated CaMKII/ERK activation contributes to renal fibrosis
Authors: Zhou Jingyi , Liu Shuaihui , Guo Luying , Wang Rending , Chen Jianghua , Shen Jia
Published: September 2020

Background

This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration.

Methods

Acute renal fibrosis (RF) was induced in mice by unilateral ureteral obstruction (UUO). Histological changes were observed using Masson’s trichrome staining. The expression levels of NR1, which is the functional subunit of NMDAR, and fibrotic and epithelial-to-mesenchymal transition markers were measured by immunohistochemical and Western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were administered for pathway determination. Chronic RF was introduced by sublethal ischemia–reperfusion injury in mice, and NMDAR inhibitor dextromethorphan hydrobromide (DXM) was administered orally.

Results

The expression of NR1 was upregulated in obstructed kidneys, while NR1 knockdown significantly reduced both interstitial volume expansion and the changes in the expression of α-smooth muscle actin, S100A4, fibronectin, COL1A1, Snail, and E-cadherin in acute RF. TGF-β1 treatment increased the elongation phenotype of HK-2 cells and the expression of membrane-located NR1 and phosphorylated CaMKII and extracellular signal–regulated kinase (ERK). MK801 and KN93 reduced CaMKII and ERK phosphorylation levels, while MK801, but not KN93, reduced the membrane NR1 signal. The levels of phosphorylated CaMKII and ERK also increased in kidneys with obstruction but were decreased by NR1 knockdown. The 4-week administration of DXM preserved renal cortex volume in kidneys with moderate ischemic–reperfusion injury.

Conclusions

NMDAR participates in both acute and chronic renal fibrogenesis potentially via CaMKII-induced ERK activation.
The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson’s disease: a single-center pilot study
Authors: Ito Hiroto , Yokoi Daichi , Kobayashi Rei , Okada Hisashi , Kajita Yasukazu , Okuda Satoshi
Published: September 2020

Background

Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson’s disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis.

Methods

Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients’ best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for “On” and “dyskinesia”.

Results

The parameter “mean METs value within the 95–92.5 percentile range on a day (95–92.5 percentile value)” exhibited the strongest correlation with conventional daily clinical ratings (Rho: − 0.799 for UPDRS-3[On], 0.803 for On hours [p < 0.001]). Scatter plots suggested that PAL tended to have higher values in patients with involuntary movement. However, METs parameters focusing on higher METs seemed to alleviate this tendency. We clarified that “time over 2.0 METs” and “time over 1.5 METs” could be predictors for “On” and “dyskinesia” on a 30-min basis, respectively (AUROC: 0.779 and 0.959, 95% CI: 0.733–0.824 and 0.918–1.000). The specificity and sensitivity of the optimal activity pattern for “On” were 0.858 and 0.621.

Conclusions

This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.
Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial
Authors: Amezcua-Prieto C. , Naveiro-Fuentes M. , Arco-Jiménez N. , Olmedo-Requena R. , Barrios-Rodríguez R. , Vico-Zúñiga I. , Manzanares Galán S. , Mozas-Moreno J. , Jiménez-Moleón J. J. , Gallo-Vallejo J. L.
Published: September 2020

Background

Previous studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy.

Methods

Randomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13–32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson’s Chi-square test or Fisher’s exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software.

Discussion

promoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved –'10,000–11,000 steps a day’– should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women.

Trial registration

ClinicalTrials.govIdentifier:NCT03735381. Registered 8th November, 2018.
Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
Authors: Davis Jennifer S. , Kanikarla-Marie Preeti , Gagea Mihai , Yu Patrick L. , Fang Dexing , Sebastian Manu , Yang Peiying , Hawk Ernest , Dashwood Roderick , Lichtenberger Lenard M. , Menter David , Kopetz Scott
Published: September 2020

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid.

Methods

As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apcmin/+ mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries.

Results

Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone.

Conclusions

Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.
Nomogram for individually predicting overall survival in rectal neuroendocrine tumours
Authors: Feng Xingyu , Wei Gengzhou , Wang Wei , Zhang Yu , Zeng Yujie , Chen Minhu , Chen Ye , Chen Jie , Zhou Zhiwei , Li Yong
Published: September 2020

Background

This study aimed to develop a nomogram that predicts the overall survival (OS) of rectal neuroendocrine tumours (NETs).

Methods

We retrospectively analysed 310 patients with rectal neuroendocrine tumours in 5 hospitals in southern China. All of the patients were assigned to the training set. A multivariable analysis using Cox proportional hazards regression was performed using the training set, and a nomogram was constructed. It was validated on a dataset obtained from the Surveillance, Epidemiology, and End Result (SEER) database of America (n = 547).

Results

In the training set, the nomogram exhibited improved discrimination power compared with the WHO grade guidelines (Herrell’s C-index, 0.872 vs 0.794; p < 0.001) and was also better than the seventh AJCC TNM classification (Herrell’s C-index, 0.872 vs 0.817; p < 0.001). In the SEER validation dataset, the discrimination was also excellent (C-index, 0.648 vs 0.583, p < 0.001 and 0.648 vs 0.603, p = 0.016, respectively, compared with G grade and TNM classification). Calibration of the nomogram predicted individual survival corresponding closely with the actual survival.

Conclusions

We developed a nomogram predicting 1- and 3-year OS of patients with rectal neuroendocrine tumours. Validation revealed excellent discrimination and calibration, suggesting good clinical utility.
Influence of automated visual field testing on intraocular pressure
Authors: Bertaud Samuel , Skarbek Borowski Elisabeth , Abbas Rachid , Baudouin Christophe , Labbé Antoine
Published: September 2020

Background

To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma.

Methods

We conducted a prospective observational study in the glaucoma department at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 min before and after VF testing. Sub analyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations.

Results

There was no significant change in IOP after VF testing, with IOP’s 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R2 = 0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (P = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation ≥2 mmHg had a significantly higher VF test duration (P = 0.002).

Conclusion

VF testing does not influence IOP as measured with a non-contact tonometer.
Knowledge gain and usage of knowledge learned during internet-based CBT treatment for adolescent depression - a qualitative study
Authors: Berg Matilda , Malmquist Anna , Rozental Alexander , Topooco Naira , Andersson Gerhard
Published: September 2020

Background

The role of explicit learning of treatment content in internet-based cognitive-behavioural treatment (ICBT) is an emerging field of research. The objective of this study was to explore clients experiences of their ICBT treatment for depression with a focus on knowledge gain and usage of knowledge learned during treatment.

Methods

A strategic sample of ten adolescents, aged between 15 and 19 years, who had received ICBT for major depression within a clinical controlled trial were recruited for the study. Semi-structured interviews were conducted 6 months following trial completion. Data were transcribed and analysed using thematic analysis. The participants had a general adherence rate of 6–8 opened modules out of 8 possible.

Results

Two main themes were identified; “Active agents of CBT” and “Passive agents of CBT”, with each theme consisting of three and two sub-themes. Active agents of CBT reflect a tendency to specifically remember and actively apply specific CBT principles in present life situations. Passive agents of CBT reflect a tendency to remember CBT treatment principles vaguely and express a passive or reactive usage of learned therapy content.

Conclusion

The findings suggest that young clients can remember and apply CBT principles 6 months after their treatment. However, while experiencing benefits of treatment, clients recall and application of treatment strategies vary. The study emphasizes the importance of exploring client recall of CBT components and how valuable it is to explicitly remember contents of a treatment in order to improve and maintain improvement. Further studies on the role of knowledge and memory of ICBT for adolescent populations are warranted.
Association between time spent in the Russian Federation and late presentation for HIV among Tajikistani migrants
Authors: Bromberg Daniel J. , Tate Mary M. , Alaei Kamiar , Karimov Saifuddin , Saidi Dilshod , Alaei Arash
Published: September 2020

Background

Between 700 thousand and 1.2 million citizens of Tajikistan currently live in the Russian Federation, one of the only countries where the HIV epidemic continues to worsen. Given the previously reported barriers to healthcare access for migrants to the Russian Federation, and the rapidly expanding HIV epidemic in Eastern Europe and Central Asia, this present study set out to determine whether these barriers impact late presentation with HIV among Tajikistani migrants upon their return to Tajikistan.

Method

This study uses data from the Tajikistan Ministry of Health surveillance system (2006 – 2019). At time of diagnosis, patients are interviewed by staff of AIDS centers, and doctors complete routine intake forms and complete medical exams. Descriptive characteristics of migrants with HIV who had lived in the Russian Federation (n=503) were calculated and compared with those of non-migrants with HIV (n=9519). Missing data were imputed using multiple imputation (predictive means matching, logistic regression imputation, and polytomous regression imputation). Two logistic models were created to model the probability of late presentation for HIV. The first model shows unadjusted associations between predictor variables and late presentation for HIV. The second model shows multivariable associations between significant study variables identified in the univariate model, and late presentation.

Results

Compared to non-migrants, migrants with HIV are more likely to be from Gorno-Badakhshan region, are less likely to use illicit drugs, and are more likely to have purchased the services of sex workers. The unadjusted logistic model found that for every year spent in the Russian Federation, the risk of late presentation for a Tajikistani migrant with HIV increases by 4.0% (95% CI: 0.3-7.7). The multivariate model showed that when age, sex, and region of origin are held constant, the risk of late presentation for a Tajikistani migrant with HIV increases by 4.0% (95% CI: 0.1-7.8) for each year spent in the Russian Federation.

Conclusion

The results of this paper suggest that if the Russian Federation were to loosen its restrictions on HIV care for foreign nationals, it might improve the treatment outcomes of migrant laborers. As this analysis is only correlational in nature, further research is needed to explicate the causal pathways of the associations found in the present analysis.
Investigating the knowledge of and public attitudes towards genetic testing within the Visegrad countries: a cross-sectional study
Authors: Bíró Klára , Dombrádi Viktor , Fekete Zita , Bányai Gábor , Boruzs Klára , Nagy Attila , Ádány Róza
Published: September 2020

Background

Previous studies have investigated various factors that can determine the attitudes of the citizens considering genetic testing. However, none of them investigated how these attitudes may differ between the Visegrad countries.

Methods

In this cross-sectional study a questionnaire developed by Dutch researchers was translated and used in Hungary, Slovakia, Czechia and Poland. In each country 1000 adult citizens were asked on the topics of personal benefits regarding genetic tests, genetic determinism, and finally, the availability and usage of genetic testing. Multivariate robust regression model was created including several possible influencing factors (such as age, sex, education, marital status, religiousness, and having a genetic test within the nuclear family) to identify the possible differences between the four countries.

Results

The Hungarian citizens had the most positive opinion on the personal benefits of genetic testing followed by the Czech, Slovak and Polish. All differences were significant in this regard. Considering genetic determinism, the Slovak citizens had a significantly firmer belief in this issue compared to the Hungarians. No other significant differences were observed in this domain. On the topic of the availability and use of genetic testing the Hungarian citizens had the most accepting opinion among the four countries, followed by the Czech citizens. In this domain the Polish and Slovak answers did not differ significantly from each other.

Conclusions

Significant differences were observed even when considering various confounding effects. As the underlying reasons for these discrepancies are unknown, future studies should investigate this enigma among the four countries.
Contact pressure distribution of the hip joint during closed reduction of developmental dysplasia of the hip: a patient-specific finite element analysis
Authors: Zhang Zhiqiang , Sui Dashan , Qin Haiyi , Li Hai , Zhang Ziming
Published: September 2020

Background

Developmental dysplasia of the hip (DDH) is the most common deformity of the lower extremity in children. The biomechanical change during closed reduction (CR) focused on cartilage contact pressure (CCP) has not been studied. Thereby, we try to provide insight into biomechanical factors potentially responsible for the success of CR treatment sand complications by using finite element analysis (FEA) for the first time.

Methods

Finite element models of one patient with DDH were established based on the data of MRI scan on which cartilage contact pressure was measured. During CR, CCP between the femoral head and acetabulum in different abduction and flexion angles were tested to estimate the efficacy and potential risk factors of avascular necrosis (AVN) following CR.

Results

A 3D reconstruction by the FEA method was performed on a 16 months of age girl with DDH on the right side. The acetabulum of the involved side showed a long, narrow, and “flat-shaped” deformity, whereas the femoral head was smaller and irregular compared with the contralateral side. With increased abduction angle, the stress of the posterior acetabulum increased significantly, and the stress on the lateral part of the femoral head increased as well. The changes of CCP in the superior acetabulum were not apparent during CR. There were no detectable differences in terms of pressure on the femoral head.

Conclusions

Severe dislocation (IHDI grade III and IV) in children showed a high mismatch between the femoral head and acetabulum. Increased abduction angle corresponded with high contact pressure, which might relate to AVN, whereas increased flexion angle was not. Enhanced pressure on the lateral part of the femoral head might increase the risk of AVN.
A prospective study on cancer risk after total hip replacements for 41,402 patients linked to the Cancer registry of Norway
Authors: Dybvik Eva , Furnes Ove , Havelin Leif I. , Fosså Sophie D. , Trovik Clement , Lie Stein Atle
Published: September 2020

Background

Concerns have been raised that implants used in total hip replacements (THR) could lead to increased cancer risk. Several different materials, metals and fixation techniques are used in joint prostheses and different types of articulation can cause an increased invasion of particles or ions into the human body.

Methods

Patients with THR registered in the Norwegian Arthroplasty Register during 1987–2009 were linked to the Cancer registry of Norway. Patients with THR due to osteoarthritis, under the age of 75 at time of surgery, were included. Standardized incidence ratios (SIR) were applied to compare cancer risk for THR patients to the general population. Types of THR were divided into cemented (both components), uncemented (both components), and hybrid (cemented femoral and uncemented acetabular components). To account for selection mechanisms, time dependent covariates were applied in Cox-regression, adjusting for cancer risk the first 10 years after surgery. The analyses were adjusted for age, gender and if the patient had additional THR-surgery in the same or the opposite hip. The study follows the STROBE guidelines.

Results

Comparing patients with THR to the general population in Norway we found no differences in cancer risk. The overall SIR for the THR-patients after 10 years follow-up was 1.02 (95% CI: 0.97–1.07). For cemented THR, the SIR after 10 years follow-up was 0.99 (95% CI: 0.94–1.05), for uncemented, 1.16 (95% CI: 1.02–1.30), and for hybrid 1.12 (95% CI: 0.91–1.33). Adjusted Cox analyses showed that patients with uncemented THRs had an elevated risk for cancer (hazard ratio: HR = 1.24, 95% CI: 1.05–1.46, p = 0.009) when compared to patients with cemented THRs after 10 years follow-up. Stratified by gender the increased risk was only present for men. The risk for patients with hybrid THRs was not significantly increased (HR = 1.07, 95% CI: 0.85–1.35, p = 0.55) compared to patients with cemented THRs.

Conclusions

THR patients had no increased risk for cancer compared to the general population. We found, however, that receiving an uncemented THR was associated with a small increased risk for cancer compared to cemented THR in males, but that this may be prone to unmeasured confounding.
A review of virtual planning software for guided implant surgery - data import and visualization, drill guide design and manufacturing
Authors: Kernen Florian , Kramer Jaap , Wanner Laura , Wismeijer Daniel , Nelson Katja , Flügge Tabea
Published: September 2020

Background

Virtual implant planning systems integrate (cone beam-) computed tomography data to assess bone quantity and virtual models for the design of the implant-retained prosthesis and drill guides. Five commercially available systems for virtual implant planning were examined regarding the modalities of integration of radiographic data, virtual dental models and the design of drill guides for guided implant surgery. The purpose of this review was to describe the limitations of these available systems regarding the import of imaging data and the design and fabrication of a drill guide.

Methods

The following software systems were examined regarding the import of imaging data and the export of the virtual implant planning for the design and fabrication of a drill guide with the help of two clinical situations requiring dental implant therapy: coDiagnostiX™, DentalWings, Canada (CDX); Simplant Pro™, Dentsply, Sweden (SIM); Smop™, Swissmeda, Switzerland (SMP); NobelClinician™, Nobel Biocare, Switzerland (NC); Implant Studio, 3Shape, Denmark (IST). Assessment criteria included data formats and management as well as the workflow for the design and production of drill guides.

Results

All systems have a DICOM-interface (“Digital Imaging and Communication in Medicine”) for the import of radiographic data. Imaging artefacts could be reduced but not eliminated by manual data processing. The import of virtual dental models in a universal format (STL: Standard Tesselation Language) was possible with three systems; one system could only be used with a proprietary data format.

All systems display three-dimensional surface models or two-dimensional cross-sections with varying orientation for virtual implant planning. Computer aided design and manufacturing (CAD/CAM) of drill guides may be performed by the user with the help of default parameters or solely by the provider of the software and thus without the influence of the clinician.

Conclusion

Data bases of commonly used implant systems are available in all tested software, however not all systems allow to plan and execute fully guided implant placement. An individual design and in-house manufacturing of the drill guide is only available in some software systems. However, at the time of publication most recent software versions showed flexibility in individual design and in-house manufacturing of drill guides.
Mandibular first premolar with five root canals: a case report
Authors: Zhang Ming , Xie Jian , Wang Yan-huang , Feng Yan
Published: September 2020

Background

Understanding the anatomical morphology of the root canal is key for successful root canal treatment. The aims of this case presentation are to report a unique case of root canal treatment involving five root canals in the mandibular first premolar and to highlight the importance of variation in root canals of mandibular first premolars in clinical practice.

Case presentation

A 25-year-old male with intermittent pain in relation to the lower right posterior teeth over 3 weeks was diagnosed with symptomatic pulpitis in tooth #44. Four root canals were found, including mesiobuccal, distobuccal-1, distobuccal-2, and distolingual roots, and the Mtwo rotary system was used for root canal preparation. The four root canals were filled after 2 weeks, when a fifth canal was found, located in the buccal cavity. The fifth canal was confirmed to be the mesiolingual root canal by cone beam computed tomography (CBCT) and was found to be curved. After completion of the root canal filling, CBCT was performed, and a three-dimensional root canal image was reconstructed. After 1 week of observation, the tooth was repaired using composite resin filling.

Conclusions

This is the first case presentation of a fifth canal of the mandibular first premolar and advances our understanding of variations in the anatomy of the mandibular first premolar. This case report provides a reference for the treatment of mandibular first premolars.
Community utilisation and satisfaction with the community-based health planning and services initiative in Ghana: a comparative study in two system learning districts of the CHPS+ project
Authors: Kweku Margaret , Amu Hubert , Adjuik Martin , Aku Fortress Yayra , Manu Emmanuel , Tarkang Elvis Enowbeyang , Komesuor Joyce , Asalu Geoffrey Adebayor , Amuna Norbert Ndaah , Boateng Laud Ampomah , Alornyo Justine Sefakor , Glover Roland , Bawah Ayaga A. , Letsa Timothy , Awoonor-Williams John Koku , Phillips James F. , Gyapong John Owusu
Published: September 2020

Background

To strengthen the implementation of the Community-based Health Planning and Services (CHPS) programme which is Ghana’s key primary health care delivery strategy, the CHPS+ Project was initiated in 2017. We examined community utilisation and satisfaction with CHPS services in two System Learning Districts (SLDs) of the project.

Methods

This community-based descriptive study was conducted in the Nkwanta South Municipality and Central Tongu District of Ghana. Data were collected from 1008 adults and analysed using frequency, percentage, chi-square, and logistic regression models.

Results

While the level of utilisation of CHPS services was 65.2%, satisfaction was 46.1%. Utilisation was 76.7% in Nkwanta South and 53.8% in Central Tongu. Satisfaction was also 55.2% in Nkwanta South and 37.1% in Central Tongu. Community members in Nkwanta South were more likely to utilise (AOR = 3.17, 95%CI = 3.98–9.76) and be satisfied (AOR = 2.77, 95%CI = 1.56–4.90) with CHPS services than those in Central Tongu. Females were more likely to utilise (AOR = 1.75, 95%CI = 1.27–2.39) but less likely to be satisfied [AOR = 0.47, 95%CI = 0.25–0.90] with CHPS services than males. Even though subscription to the National Health Insurance Scheme (NHIS) was just 46.3%, NHIS subscribers were more likely to utilise (AOR = 1.51, 95%CI = 1.22–2.03) and be satisfied (AOR = 1.45, 95%CI = 0.53–1.68) with CHPS services than non-subscribers.

Conclusion

Ghana may not be able to achieve the goal of universal health coverage (UHC) by the year 2030 if current levels of utilisation and satisfaction with CHPS services persist. To accelerate progress towards the achievement of UHC with CHPS as the vehicle through which primary health care is delivered, there should be increased public education by the Ghana Health Service (GHS) on the CHPS concept to increase utilisation. Service quality should also be improved by the GHS and other stakeholders in Ghana’s health industry to increase satisfaction with CHPS services. The GHS and the National Health Insurance Authority (NHIA) should also institute innovative strategies to increase subscription to the NHIS since it has implications for CHPS service utilisation and satisfaction.
Collaborative care for mental health: a qualitative study of the experiences of patients and health professionals
Authors: Rugkåsa Jorun , Tveit Ole Gunnar , Berteig Julie , Hussain Ajmal , Ruud Torleif
Published: September 2020

Background

Health policy in many countries directs treatment to the lowest effective care level and encourages collaboration between primary and specialist mental health care. A number of models for collaborative care have been developed, and patient benefits are being reported. Less is known about what enables and prevents implementation and sustainability of such models regarding the actions and attitudes of stakeholders on the ground. This article reports from a qualitative sub-study of a cluster-RCT testing a model for collaborative care in Oslo, Norway. The model involved the placement of psychologists and psychiatrists from a community mental health centre in each intervention GP practice. GPs could seek their input or advice when needed and refer patients to them for assessment (including assessment of the need for external services) or treatment.

Methods

We conducted in-depth qualitative interviews with GPs (n = 7), CMHC specialists (n = 6) and patients (n = 11) in the intervention arm. Sample specific topic guides were used to investigate the experience of enablers and barriers to the collaborative care model. Data were subject to stepwise deductive-inductive thematic analysis.

Results

Participants reported positive experiences of how the model improved accessibility. First, co-location made GPs and CMHC specialists accessible to each other and facilitated detailed, patient-centred case collaboration and learning through complementary skills. The threshold for patients’ access to specialist care was lowered, treatment could commence early, and throughput increased. Treatment episodes were brief (usually 5–10 sessions) and this was too brief according to some patients. Second, having experienced mental health specialists in the team and on the front line enabled early assessment of symptoms and of the type of treatment and service that patients required and were entitled to, and who could be treated at the GP practice. This improved both care pathways and referral practices. Barriers revolved around the organisation of care. Logistical issues could be tricky but were worked out. The biggest obstacle was the funding of health care at a structural level, which led to economic losses for both the GP practices and the CMHC, making the model unsustainable.

Conclusions

Participants identified a range of benefits of collaborative care for both patients and services. However, the funding system in effect penalises collaborative work. It is difficult to see how policy aiming for successful, sustainable collaboration can be achieved without governments changing funding structures.

Trial registration

ClinicalTrials.gov identifier: NCT03624829.
Aneuploidy-induced proteotoxic stress can be effectively tolerated without dosage compensation, genetic mutations, or stress responses
Authors: Larrimore Katherine E. , Barattin-Voynova Natalia S. , Reid David W. , Ng Davis T. W.
Published: September 2020

Background

The protein homeostasis (proteostasis) network maintains balanced protein synthesis, folding, transport, and degradation within a cell. Failure to maintain proteostasis is associated with aging and disease, leading to concerted efforts to study how the network responds to various proteotoxic stresses. This is often accomplished using ectopic overexpression of well-characterized, model misfolded protein substrates. However, how cells tolerate large-scale, diverse burden to the proteostasis network is not understood. Aneuploidy, the state of imbalanced chromosome content, adversely affects the proteostasis network by dysregulating the expression of hundreds of proteins simultaneously. Using aneuploid haploid yeast cells as a model, we address whether cells can tolerate large-scale, diverse challenges to the proteostasis network.

Results

Here we characterize several aneuploid Saccharomyces cerevisiae strains isolated from a collection of stable, randomly generated yeast aneuploid cells. These strains exhibit robust growth and resistance to multiple drugs which induce various forms of proteotoxic stress. Whole genome re-sequencing of the strains revealed this was not the result of genetic mutations, and transcriptome profiling combined with ribosome footprinting showed that genes are expressed and translated in accordance to chromosome copy number. In some strains, various facets of the proteostasis network are mildly upregulated without chronic activation of environmental stress response or heat shock response pathways. No severe defects were observed in the degradation of misfolded proteins, using model misfolded substrates of endoplasmic reticulum-associated degradation or cytosolic quality control pathways, and protein biosynthesis capacity was not impaired.

Conclusions

We show that yeast strains of some karyotypes in the genetic background studied here can tolerate the large aneuploidy-associated burden to the proteostasis machinery without genetic changes, dosage compensation, or activation of canonical stress response pathways. We suggest that proteotoxic stress, while common, is not always an obligate consequence of aneuploidy, but rather certain karyotypes and genetic backgrounds may be able to tolerate the excess protein burden placed on the protein homeostasis machinery. This may help clarify how cancer cells are paradoxically both highly aneuploid and highly proliferative at the same time.
MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy
Authors: Ait-Aissa Karima , Nguyen Quynh My , Gabani Mohanad , Kassan Adam , Kumar Santosh , Choi Soo-Kyoung , Gonzalez Alexis A. , Khataei Tahsin , Sahyoun Amal M. , Chen Cheng , Kassan Modar
Published: September 2020

The endothelium plays a pivotal role in maintaining vascular health. Obesity is a global epidemic that has seen dramatic increases in both adult and pediatric populations. Obesity perturbs the integrity of normal endothelium, leading to endothelial dysfunction which predisposes the patient to cardiovascular diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNA molecules that play important roles in a variety of cellular processes such as differentiation, proliferation, apoptosis, and stress response; their alteration contributes to the development of many pathologies including obesity. Mediators of obesity-induced endothelial dysfunction include altered endothelial nitric oxide synthase (eNOS), Sirtuin 1 (SIRT1), oxidative stress, autophagy machinery and endoplasmic reticulum (ER) stress. All of these factors have been shown to be either directly or indirectly caused by gene regulatory mechanisms of miRNAs. In this review, we aim to provide a comprehensive description of the therapeutic potential of miRNAs to treat obesity-induced endothelial dysfunction. This may lead to the identification of new targets for interventions that may prevent or delay the development of obesity-related cardiovascular disease.
Comparative metabolomics of Phialemonium curvatum as an omnipotent fungus cultivated on crude palm oil versus glucose
Authors: Zamani Arief Izzairy , Barig Susann , Ibrahim Sarah , Mohd. Yusof Hirzun , Ibrahim Julia , Low Jaime Yoke Sum , Kua Shwu Fun , Baharum Syarul Nataqain , Stahmann Klaus-Peter , Ng Chyan Leong
Published: September 2020

Background

Sugars and triglycerides are common carbon sources for microorganisms. Nonetheless, a systematic comparative interpretation of metabolic changes upon vegetable oil or glucose as sole carbon source is still lacking. Selected fungi that can grow in acidic mineral salt media (MSM) with vegetable oil had been identified recently. Hence, this study aimed to investigate the overall metabolite changes of an omnipotent fungus and to reveal changes at central carbon metabolism corresponding to both carbon sources.

Results

Targeted and non-targeted metabolomics for both polar and semi-polar metabolites of Phialemonium curvatum AWO2 (DSM 23903) cultivated in MSM with palm oil (MSM-P) or glucose (MSM-G) as carbon sources were obtained. Targeted metabolomics on central carbon metabolism of tricarboxylic acid (TCA) cycle and glyoxylate cycle were analysed using LC–MS/MS-TripleQ and GC–MS, while untargeted metabolite profiling was performed using LC–MS/MS-QTOF followed by multivariate analysis. Targeted metabolomics analysis showed that glyoxylate pathway and TCA cycle were recruited at central carbon metabolism for triglyceride and glucose catabolism, respectively. Significant differences in organic acids concentration of about 4- to 8-fold were observed for citric acid, succinic acid, malic acid, and oxaloacetic acid. Correlation of organic acids concentration and key enzymes involved in the central carbon metabolism was further determined by enzymatic assays. On the other hand, the untargeted profiling revealed seven metabolites undergoing significant changes between MSM-P and MSM-G cultures.

Conclusions

Overall, this study has provided insights on the understanding on the effect of triglycerides and sugar as carbon source in fungi global metabolic pathway, which might become important for future optimization of carbon flux engineering in fungi to improve organic acids production when vegetable oil is applied as the sole carbon source.
LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis
Authors: Chen Xia , Yang Jingxiu , Wang Yuping
Published: September 2020

Background

The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown.

Method

In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC.

Results

We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4.

Conclusions

Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.
Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India
Authors: Rehman Asad Ur , Iqbal Mohammad Askandar , Sattar Real Sumayya Abdul , Saikia Snigdha , Kashif Mohammad , Ali Wasif Mohammad , Medhi Subhash , Saluja Sundeep Singh , Husain Syed Akhtar
Published: September 2020

Background

Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer.

Methods

Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR.

Results

Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient’s tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001).

Conclusion

The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.
Implementation of a malaria sentinel surveillance system in Togo: a pilot study
Authors: Thomas Anne , Bakai Tchaa A. , Atcha-Oubou Tinah , Tchadjobo Tchassama , Voirin Nicolas
Published: September 2020

Background

In Togo, the National Malaria Control Programme, in collaboration with the Global Fund to Fight AIDS, Tuberculosis and Malaria, has implemented a pilot study for malaria sentinel surveillance since 2017, which consists of collecting information in real time and analysing this information for decision-making. The first 20 months of malaria morbidity and mortality trends, and malaria case management in health facilities included in the surveillance were assessed.

Methods

Since July 2017, 16 health facilities called sentinel sites, 4 hospitals and 12 peripheral care units located in 2 epidemiologically different health regions, have provided weekly data on malaria morbidity and mortality for the following 3 target groups: < 5-years-old children, ≥ 5-years-old children and adults, and pregnant women. Data from week 29 in 2017 to week 13 in 2019 were analysed.

Results

Each sentinel site provided complete data and the median time to data entry was 4 days. The number of confirmed malaria cases increased during the rainy seasons both in children under 5 years old and in children over 5 years old and adults. Malaria-related deaths occurred mainly in children under 5 years old and increased during the rainy seasons. The mean percentage of tested cases for malaria among suspected malaria cases was 99.0%. The mean percentage of uncomplicated malaria cases handled in accordance with national guidelines was 99.4%. The mean percentage of severe malaria cases detected in peripheral care units that were referred to a hospital was 100.0%. Rapid diagnostic tests and artemisinin-based combination therapies were out of stock several times, mainly at the beginning and end of the year. No hospital was out of stock of injectable artesunate or injectable artemether.

Conclusions

These indicators showed good management of malaria cases in the sentinel sites. Real-time availability of data requires a good follow-up of data entry on the online platform. The management of input stocks and the promptness of data need to be improved to meet the objectives of this malaria sentinel surveillance system.