bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful monozygotic triplet pregnancy after a single blastocyst transfer following in vitro maturation of oocytes from a woman with polycystic ovary syndrome: a case report
Authors: Ota Kuniaki , Takahashi Toshifumi , Katagiri Mikiko , Matsuoka Ryu , Sekizawa Akihiko , Mizunuma Hideki , Yoshida Hiroaki
Published: January 2020

Background

Although women with polycystic ovarian syndrome (PCOS)-related sub-fertility are high responders to controlled ovarian stimulation, it is difficult to obtain mature oocytes in these women. Therefore, in vitro maturation (IVM), which is the technique of letting the contents of the ovarian follicles and the oocytes inside mature in vitro, has often been proposed in such women. We describe the first successful delivery of monozygotic triplets resulting from transfer of a single blastocyst following IVM of oocytes.

Case presentation

A 32-year-old nulligravida female with PCOS underwent IVM. She underwent vitrified-warmed single blastocyst transfer following IVM, and a dichorionic triamniotic triplet pregnancy was confirmed at 8 weeks. Healthy triplets were delivered by cesarean section at 33 weeks’ gestation. This is the first case of monozygotic triplets derived from IVM oocytes that were successfully delivered. The determination of chorionicity and amnionicity is generally supposed until 3 days after fertilization, and no division or splitting of her embryo was observed on transfer. Interestingly, her embryo might have split after the transfer, resulting in a dichorionic triamniotic triplet pregnancy.

Conclusions

Patients should be informed of a possible increased risk of monozygotic multiple pregnancies after single embryo transfer following IVM.
Women’s knowledge of and attitudes toward cervical cancer and cervical cancer screening in Zanzibar, Tanzania: a cross-sectional study
Authors: Weng Qiao , Jiang Jie , Haji Fatma Mrisho , Nondo Lamlet Hassan , Zhou Huaijun
Published: January 2020

Background

Cervical cancer is the most common cancer and the leading cause of cancer death among women in Tanzania. Knowledge of and willingness to receive a cervical cancer screening are important determinants of prevention. This study aimed to describe women’s awareness of cervical cancer and to explore the attitudes toward, acceptability of and barriers to cervical cancer screening (CCS) in Zanzibar.

Methods

A cross-sectional study was conducted from March to June 2018 involving 1483 women from 10 districts in Zanzibar who responded to questionnaires concerning their general demo-graphic characteristics, screening willingness and awareness of cervical cancer. Chi-square tests, analysis of variance (ANOVA) and stepwise multiple regression were conducted using STATA 15.1 software.

Results

The average total knowledge score (TKS) was 7.84 ± 5.32 on a 23-point scale. Educational level and family income were positively correlated with the TKS. Previous schistosomiasis history and family genetic disease history were strong predictors of screening willingness. Women were less likely to be screened freely if they had 7 or more deliveries and were unaware of any previous family tumor history. Age and educational level were negatively associated non-free screening willingness, while family income was positively associated; being divorced/widowed or single and being unaware of any previous family tumor history were predictors of screening reluctance, while previous disease history was a strong predictor of non-free screening willingness. Fear of screening and inconvenience were the primary concerns among the Zanzibari interviewees. Compared to the 20–49 age group, more women in the less than 20 and 50 or more age groups thought cervical cancer screening was not necessary. The highest rate of cognitive accuracy in regard to cervical cancer warning signs and risk factors was only 37.76%.

Conclusions

The findings revealed that knowledge of cervical cancer was poor. Educational level, family income and awareness of previous disease history were significant influencing factors of screening uptake. Specific awareness programs to increase knowledge of cervical cancer and screening willingness should be designed and implemented in the public without delay, especially for younger and elderly women.
Superiority of NBI endoscopy to PET/CT scan in detecting esophageal cancer among head and neck cancer patients: a retrospective cohort analysis
Authors: Su Hsuan-An , Hsiao Shun-Wen , Hsu Yu-Chun , Wang Lien-Yen , Yen Hsu-Heng
Published: January 2020

Background

Second primary cancer of the esophagus is frequent in head and neck patients, especially in high-risk populations, and has a great impact on the prognosis. Although Positron emission tomography (PET)/computed tomography (CT) scan is commonly conducted in head and neck patients, its ability to detect early esophageal cancer is limited. Narrow-band imaging endoscopy is an accurate and convenient technique for esophageal examination. We aimed to compare PET/CT scan and narrow-band imaging endoscopy for the detection of esophageal cancer in head and neck cancer patients.

Methods

From November 2015 to November 2018, all head and neck cancer patients who underwent both PET/CT scan and narrow-band imaging endoscopy at Changhua Christian Hospital were retrospectively enrolled. Descriptive statistics, receiver operating characteristic curve analysis, logistic regression analysis, independent Student’s t-test, and Kaplan–Meier survival analysis were conducted with MedCalc Statistical Software.

Results

A total of 147 subjects were included in the analysis; suspicious esophageal lesions were identified by PET/CT scan in 8 (5.44%) and by narrow-band imaging in 35 (23.81%). The final pathologic diagnoses were esophageal squamous cell carcinoma in 10 and high-grade dysplasia in 5. The respective sensitivity, specificity, and area under the curve for detecting suspicious esophageal lesions were 33.33, 97.73%, and 0.655 for PET/CT scan, and 100.0, 84.85%, and 0.924 for narrow-band imaging endoscopy. Hypopharyngeal or laryngeal location of the primary head and neck cancer was the only risk factor for developing second primary esophageal cancer.

Conclusions

PET/CT scan was inferior to narrow-band imaging endoscopy in detecting second primary esophageal cancer in head and neck cancer patients. In addition to PET/CT scan, narrow-band imaging endoscopy should be considered in head and neck patients at high risk for developing second primary esophageal cancer.
The neurocognitive function change criteria after whole-brain radiation therapy for brain metastasis, in reference to health-related quality of life changes: a prospective observation study
Authors: Nakano Toshimichi , Aoyama Hidefumi , Saito Hirotake , Tanabe Satoshi , Tanaka Kensuke , Maruyama Katsuya , Oshikane Tomoya , Ohta Atsushi , Abe Eisuke , Kaidu Motoki
Published: January 2020

Background

We sought to construct the optimal neurocognitive function (NCF) change criteria sensitive to health-related quality of life (HR-QOL) in patients who have undergone whole-brain radiation therapy (WBRT) for brain metastasis.

Methods

We categorized the patients by the changes of NCF into groups of improvement versus deterioration if at least one domain showed changes that exceeded the cut-off while other domains remained stable. The remaining patients were categorized as stable, and the patients who showed both significant improvement and deterioration were categorized as ‘both.’ We examined the clinical meaning of NCF changes using the cut-off values 1.0, 1.5, and 2.0 SD based on the percentage of patients whose HR-QOL changes were ≥ 10 points.

Results

Baseline, 4-month and 8-month data were available in 78, 41 (compliance; 85%), and 29 (81%) patients, respectively. At 4 months, improvement/stable/deterioration/both was seen in 15%/12%/41%/32% of the patients when 1.0 SD was used; 19%/22%/37%/22% with 1.5 SD, and 17%/37%/37%/9% with 2.0 SD. The HR-QOL scores on the QLQ-C30 functional scale were significantly worse in the deterioration group versus the others with 1.0 SD (p = 0.013) and 1.5 SD (p = 0.015). With 1.5 SD, the HR-QOL scores on the QLQ-BN20 was significantly better in the improvement group versus the others (p = 0.033). However, when ‘both’ was included in ‘improvement’ or ‘deterioration,’ no significant difference in HR-QOL was detected.

Conclusions

The NCF cut-off of 1.5 SD and the exclusion of ‘both’ patients from the ‘deterioration’ and ‘improvement’ groups best reflects HR-QOL changes.
Children still experience pain during hospital stay: a cross-sectional study from four countries in Europe
Authors: Vejzovic V. , Bozic J. , Panova G. , Babajic M. , Bramhagen A-C
Published: January 2020

Background

Little is known whether children experience pain during hospital stay from the child’s own perspective or not. The existing studies tend to be based on a small number of children and therefore have limitations concerning the generalisability of the results.

Aim

The aim of this study was to describe children’s self-reported pain and experience concerning pain management during hospital stay.

Methods

This study has a quantitative cross-sectional design with descriptive statistics as data analysis.

Results

A total of 786 questionnaires, Pain in Children in Hospital, were distributed in four countries with the response rate of 75% which was almost equal between countries. Our result showed that 87% (503/579) children at hospital self-reported pain during the past 24 h. Nearly 63% of the children reported a pain score of > 5 the last 24 h. Most of children reported that they had received a question about pain from the hospital staff, and that the staff observed and assessed their pain. Totally 95% reported that they were satisfied with their pain relief during the last 24 h.

Conclusion

Our study showed that when children were given the possibility to self-report pain, nearly 2/3 expressed that they had experienced pain during hospital stay. However, most of them reported satisfaction with pain management and their pain relief.
Cognitive testing of the PHQ-9 for depression screening among pregnant and postpartum women in Kenya
Authors: Velloza Jennifer , Njoroge John , Ngure Kenneth , Thuo Nicholas , Kiptinness Catherine , Momanyi Richard , Ayub Snaidah , Gakuo Stephen , Mugo Nelly , Simoni Jane , Heffron Renee
Published: January 2020

Background

African women face high rates of depression, particularly during pregnancy or postpartum or after a recent HIV diagnosis. The Patient Health Questionnaire-9 (PHQ-9) depression screening tool has been quantitatively validated and extensively used to identify depression and link individuals to care. However, qualitative work is necessary to identify important opportunities to improve PHQ-9 question comprehension and performance among Kenyan women.

Methods

We administered the Kiswahili or English PHQ-9 (based on preference) to 29 pregnant and postpartum women in Thika, Kenya. Following administration, we conducted cognitive interviews with a purposive sample of 20 women. We used analytic memos and data matrices to identify themes around scale acceptability, comprehension, and decision and response processes.

Results

Most participants preferred to answer the PHQ-9 in Kiswahili (N = 15; 52%). Among the 20 interview participants, 12 (60%) had scores ≥5, indicating depressive symptoms. Overall, participants found the scale acceptable as an interviewer-administered tool. Participants reported few problems related to comprehension but had difficulty answering items not relevant to their lives (e.g., “watching television”) and double-barreled items (e.g., “poor appetite or overeating”). They were hesitant to endorse items related to “duties as a wife and mother” and suicidal ideation. Most participants had difficulty distinguishing between response options of “several days” and “more than half the days”.

Conclusions

We detected several problems related to PHQ-9 comprehension, decision processes, and response processes. We provide recommended changes to instructions and item wording to improve PHQ-9 validity among Kenyan women.
The epidemiology of listeriosis in pregnant women and children in New Zealand from 1997 to 2016: an observational study
Authors: Jeffs Emma , Williman Jonathan , Brunton Cheryl , Gullam Joanna , Walls Tony
Published: January 2020

Background

Listeria monocytogenes causes the foodborne infection listeriosis. Pregnant women, infants and immunocompromised children are at increased risk for infection. The aim of this study was to describe the trends in the epidemiology of disease notifications and hospital admissions due to listeriosis in pregnant women aged 15 to 45 years and children aged less than 15 years in New Zealand (NZ) from 1997 to 2016.

Methods

In this population-based descriptive study, listeriosis notification and hospitalization rates from 1997 to 2016 were analyzed. Notification data were extracted from the Institute of Environmental Science and Research (ESR) Notifiable Diseases Database (EpiSurv) and hospitalization data were extracted from the National Minimum Dataset (NMDS). Pregnant women aged 15 to 45 years and children less than 15 years of age were included. Subgroup analysis was conducted for age and ethnicity. Outcomes of infection were described.

Results

In the 20-year period considered, there were 147 pregnancy-associated cases of listeriosis either notified to ESR (n = 106) and/or coded in the NMDS (n = 99), giving a crude incidence rate of 12.3 (95% CI 10.4, 14.4) per 100,000 births. In addition, there were 22 cases in children aged 28 days to < 15 years (incidence =0.12, 95% CI 0.08 to 0.19 per 100,000). There were no trends observed over time in the incidence of pregnancy-associated listeriosis. Incidence rates of pregnancy-associated and childhood listeriosis were highest in people of Pacific and Asian ethnicity.

Conclusions

NZ has a low incidence of listeriosis in pregnant women and children, however, the consequences of infection are frequently severe. Those of Pacific and Asian ethnicity have the highest rates of disease and future messaging around food safety should target these groups. This study provides important insights into the epidemiology of listeriosis in pregnant women and children in NZ.
Desaturation during exercise is not a sufficient mechanism for prediction of osteoporosis in non-cystic fibrosis bronchiectasis
Authors: Tomlinson Owen W. , Vlachopoulos Dimitris
Published: January 2020

Background

Recent research has proposed an association between desaturation during a six minute walking test (6MWT) and osteoporosis in an elderly group of individuals with non-cystic fibrosis bronchiectasis. A causative pathway through activation of hypoxia-inducible factor 1-alpha (HIF-1α) has been proposed.

Commentary

Queries regarding the statistical approaches used are identified and discussed within this correspondence. These predominate around the use of linear regression models to predict osteoporosis in a group that is already osteoporotic, presenting with extreme values for bone mineral density (BMD). Further queries are raised regarding the HIF-1α pathway, and physical activity (PA) is proposed as an upstream mechanism for both reduced exercise tolerance and low BMD.

Conclusions

It is suggested that osteoporosis cannot be predicted in a group that is already osteoporotic, and that PA is likely to be the causative mechanism between desaturation in the 6MWT and low BMD in non-cystic fibrosis bronchiectasis.
Dentists’ clinical decision-making about teeth with apical periodontitis using a variable-controlled survey model in South Korea
Authors: Lee Junghoon , Kang Sumi , Jung Hoi-In , Kim Sunil , Karabucak Bekir , Kim Euiseong
Published: January 2020

Background

This study, by using a variable-controlled survey model, sought to compare clinical decisions made by dentists with different clinical backgrounds in South Korea regarding teeth with apical periodontitis and to identify factors that influenced decision-making.

Methods

A questionnaire with 36 questions about identical patient information, clinical signs, and symptoms was filled out by participants. Each question referred to a radiograph that had been manipulated using computer software in order to control tooth-related factors. Participants were instructed to record their demographic information and choose the ideal treatment option related to each radiograph. Simple and multivariable logistic regression analyses (p < .05) were used to investigate factors related to the decision to extract the tooth. We divided factors into dentist-related factors (gender, years of experience, and professional registration) and tooth-related factors (tooth position, coronal status, root canal filling status, and size of the periapical radiolucency). Dentists were categorized into three groups, based on professional registration: general dental practitioners (GDPs), endodontists, and other specialists. Simple logistic regression analysis (p < .05) was used to evaluate the tooth-related factors influencing extraction, depending on the dentists’ specialty.

Results

Participants mostly preferred saving the teeth over extraction. This preference was highest among the endodontists, followed by other specialists and GDPs. Extractions were significantly preferred for molars, teeth with previous root canal fillings, and those with apical lesions greater than 5 mm.

Conclusions

This study suggests that dentists’ decision-making regarding teeth with apical periodontitis was associated with their work experience and specialty and influenced by tooth position, root canal filling status, and size of the apical lesion.

Clinical relevance

This survey revealed that clinical decision-making related to teeth with apical periodontitis was affected by dentists’ specialty and work experience and by tooth-related factors, such as tooth position, root canal filling status, and size of the apical lesion.
Mitochondrial dependent pathway is involved in the protective effects of carboxymethylated chitosan on nitric oxide-induced apoptosis in chondrocytes
Authors: He Bin , Wu Fei , Li Xiaohai , Liu Yang , Fan Li , Li Haohuan
Published: January 2020

Background

Chondrocyte apoptosis activated by the mitochondrial dependent pathway serves a crucial role in cartilage degeneration of osteoarthritis (OA). In the present study, the protective effects of CMCS against sodium nitroprusside (SNP)-induced chondrocyte apoptosis were evaluated and the underlying molecular mechanisms were elucidated.

Methods

Chondrocytes were isolated from articular cartilage of SD rats and identified by type II collagen immunohistochemistry. The chondrocytes stimulated with or without SNP to induce apoptosis, were treated by CMCS for various concentrations. The cell viability were determined by MTT and LDH assays. Cell apoptotic ratio was determined by Annexin V-FITC/PI staining. Mitochondrial membrane potential (ΔΨm) was detected by using Rhodamine123 (Rho123) staining. To understand the mechanism, the mRNA expression levels of Bcl-2, Bax, cytochrome c (Cyt c) and cleaved caspase-3 were detected by real-time PCR and western blot analysis, respectively.

Results

It was shown using the MTT and LDH assays that CMCS protected the viability of chondrocyte against SNP damage. Annexin V-FITC/PI and Rho123 staining showed that CMCS not only inhibited the cell apoptosis but also restored the reduction of the ΔΨm in chondrocytes. In SNP-induced chondrocytes, CMCS down-regulated the expression of Bax, Cyt c and cleaved caspase-3 but upregulated the expression of Bcl-2, as shown by real-time PCR and western blot.

Conclusions

Taken together, these results indicated that CMCS has the protective effect on chondrocytes against SNP-induced apoptosis, at least partly, via inhibiting the mitochondrial dependent apoptotic pathway. Thus, CMCS may be potentially used as a biological agent for prevention and treatment of OA.
A case report of a mild form of multiple acyl-CoA dehydrogenase deficiency due to compound heterozygous mutations in the ETFA gene
Authors: Chautard Robin , Laroche-Raynaud Cécile , Lia Anne-Sophie , Chazelas Pauline , Derouault Paco , Sturtz Franck , Baaj Yasser , Veauville-Merllié Alice , Acquaviva Cécile , Favreau Frédéric , Faye Pierre-Antoine
Published: January 2020

Background

Multiple acyl-CoA dehydrogenase deficiency (MADD), previously called glutaric aciduria type II, is a rare congenital metabolic disorder of fatty acids and amino acids oxidation, with recessive autosomal transmission. The prevalence in the general population is estimated to be 9/1,000,000 and the prevalence at birth approximately 1/200,000. The clinical features of this disease are divided into three groups of symptoms linked to a defect in electron transfer flavoprotein (ETF) metabolism. In this case report, we present new pathogenic variations in one of the two ETF protein subunits, called electron transfer flavoprotein alpha (ETFA), in a childhood-stage patient with no antecedent.

Case presentation

A five-year-old child was admitted to the paediatric emergency unit for seizures without fever. He was unconscious due to hypoglycaemia confirmed by laboratory analyses. At birth, he was a eutrophic full-term new-born with a normal APGAR index (score for appearance, pulse, grimace, activity, and respiration). He had one older brother and no parental consanguinity was reported. A slight speech acquisition delay was observed a few months before his admission, but he had no schooling problems. MADD was suspected based on urinary organic acids and plasma acylcarnitine analyses and later confirmed by genetic analysis, which showed previously unreported ETFA gene variations, both heterozygous (c.354C > A (p.Asn118Lys) and c.652G > A (p.Val218Met) variations). Treatment was based on avoiding fasting and a slow carbohydrate-rich evening meal associated with L-carnitine supplementation (approximately 100 mg/kg/day) for several weeks. This treatment was maintained and associated with riboflavin supplementation (approximately 150 mg/day). During follow up, the patient exhibited normal development and normal scholastic performance, with no decompensation.

Conclusion

This case report describes new pathogenic variations of the ETFA gene. These compound heterozygous mutations induce the production of altered proteins, leading to a mild form of MADD.
Development and characterization of Escherichia coli triple reporter strains for investigation of population heterogeneity in bioprocesses
Authors: Heins Anna-Lena , Reyelt Jan , Schmidt Marlen , Kranz Harald , Weuster-Botz Dirk
Published: January 2020

Background

Today there is an increasing demand for high yielding robust and cost efficient biotechnological production processes. Although cells in these processes originate from isogenic cultures, heterogeneity induced by intrinsic and extrinsic influences is omnipresent. To increase understanding of this mechanistically poorly understood phenomenon, advanced tools that provide insights into single cell physiology are needed.

Results

Two Escherichia coli triple reporter strains have been designed based on the industrially relevant production host E. coli BL21(DE3) and a modified version thereof, E. coli T7E2. The strains carry three different fluorescence proteins chromosomally integrated. Single cell growth is followed with EmeraldGFP (EmGFP)-expression together with the ribosomal promoter rrnB. General stress response of single cells is monitored by expression of sigma factor rpoS with mStrawberry, whereas expression of the nar-operon together with TagRFP657 gives information about oxygen limitation of single cells. First, the strains were characterized in batch operated stirred-tank bioreactors in comparison to wildtype E. coli BL21(DE3). Afterwards, applicability of the triple reporter strains for investigation of population heterogeneity in bioprocesses was demonstrated in continuous processes in stirred-tank bioreactors at different growth rates and in response to glucose and oxygen perturbation simulating gradients on industrial scale. Population and single cell level physiology was monitored evaluating general physiology and flow cytometry analysis of fluorescence distributions of the triple reporter strains. Although both triple reporter strains reflected physiological changes that were expected based on the expression characteristics of the marker proteins, the triple reporter strain based on E. coli T7E2 showed higher sensitivity in response to environmental changes. For both strains, noise in gene expression was observed during transition from phases of non-growth to growth. Apparently, under some process conditions, e.g. the stationary phase in batch cultures, the fluorescence response of EmGFP and mStrawberry is preserved, whereas TagRFP657 showed a distinct response.

Conclusions

Single cell growth, general stress response and oxygen limitation of single cells could be followed using the two triple reporter strains developed in this study. They represent valuable tools to study population heterogeneity in bioprocesses significantly increasing the level of information compared to the use of single reporter strains.
Long noncoding RNA SNHG17 induced by YY1 facilitates the glioma progression through targeting miR-506-3p/CTNNB1 axis to activate Wnt/β-catenin signaling pathway
Authors: Li Huixia , Li Tianhao , Huang Dehai , Zhang Peng
Published: January 2020

Background

Glioma is one of the most widely diagnosed malignancies worldwide. It has been reported that long noncoding RNAs (lncRNAs) are participators in the tumorgenesis of cancers. Nevertheless, the role and function of lncRNA SNHG17 among glioma is unclear.

Methods

RT-qPCR revealed SNHG17, YY1, miR-506-3p, CTNNB1 expression among glioma cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and western blot assays revealed the function of SNHG17 in glioma. RIP uncovered SNHG17, miR-506-3p and CTNNB1 enrichment in RISC complex. Luciferase reporter assays and RNA pull down revealed interaction of miR-506-3p with SNHG17 and CTNNB1.

Results

SNHG17 expression was up-regulated in glioma tissues and cells. SNHG17 silence attenuated cell proliferation and promoted apoptosis and repressed tumor growth. Moreover, SNHG17 was up-regulated by transcription factor YY1. Mechanistically, SNHG17 activated Wnt/β-catenin signaling pathway in glioma. CTNNB1 was referred to as the mRNA of β-catenin, we validated that SNHG17 bound to miR-506-3p to induce CTNNB1 and activate Wnt/β-catenin signaling pathway. Rescue experiments indicated that CTNNB1 overexpression abolished the inhibitory effects of SNHG7 inhibition on glioma progression.

Conclusions

The findings that YY1-induced SNHG17 facilitated the glioma progression through targeting miR-506-3p/CTNNB1 axis to activate Wnt/β-catenin signaling pathway offered a brand-new prospects to molecular-targeted treatment for glioma.
Molecular methods for tracking residual Plasmodium falciparum transmission in a close-to-elimination setting in Zanzibar
Authors: Grossenbacher Benjamin , Holzschuh Aurel , Hofmann Natalie E. , Omar Kali Abdullah , Stuck Logan , Fakih Bakar Shariff , Ali Abdullah , Yukich Joshua , Hetzel Manuel W. , Felger Ingrid
Published: January 2020

Background

Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. A method comparison was undertaken to identify the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs.

Methods

In a reactive case detection study conducted on Zanzibar, parasitaemia of 4590 individuals of all ages was investigated by a highly sensitive quantitative (q) PCR that targets multiple var gene copies per parasite genome. To reduce cost, a first round of positivity screening was performed on pools of dried blood spots from five individuals. Ten cycles of a pre-PCR were performed directly on the filter paper punches, followed by qPCR. In a second round, samples of positive pools were individually analysed by pre-PCR and qPCR.

Results

Prevalence in household members and neighbors of index cases was 1.7% (78/4590) with a geometric mean parasite density of 58 parasites/µl blood. Using qPCR as gold standard, diagnostic sensitivity of rapid diagnostic tests (RDTs) was 37% (29/78). Infections positive by qPCR but negative by RDT had mean densities of 15 parasites/µl blood.

Conclusion

The approach of pre-screening reactive case detection samples in pools of five was ideal for a low prevalence setting such as in Zanzibar. Performing direct PCR on filter paper punches saves substantial time and justifies the higher cost for a polymerase suitable for amplifying DNA directly from whole blood. Molecular monitoring in community samples provided a more accurate picture of infection prevalence, as it identified a potential reservoir of infection that was largely missed by RDT. The developed qPCR-based methodology for screening large sample sets represents primarily a research tool that should inform the design of malaria elimination strategies. It may also prove beneficial for diagnostic tasks in surveillance-response activities.
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria
Authors: Delic Denis , Wunderlich Frank , Al-Quraishy Saleh , Abdel-Baki Abdel-Azeem S. , Dkhil Mohamed A. , Araúzo-Bravo Marcos J.
Published: January 2020

Background

Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver.

Methods

Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106P. chabaudi-parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i.

Results

Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd, Rhag, Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1, Ahsp, Acyp1, Gata1, Gfi1b, Tal1, Klf1, Epor, and Cldn13. In vaccination-protected mice, expression of these genes, except Epb4.1, is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i., before declining towards the end of crisis phase on day 11 p.i.

Conclusion

The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1–2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi.
Too poor or too far? Partitioning the variability of hospital-based childbirth by poverty and travel time in Kenya, Malawi, Nigeria and Tanzania
Authors: Wong Kerry L. M. , Brady Oliver J. , Campbell Oona M. R. , Banke-Thomas Aduragbemi , Benova Lenka
Published: January 2020

Background

In sub-Saharan Africa, women are most likely to receive skilled and adequate childbirth care in hospital settings, yet the use of hospital for childbirth is low and inequitable. The poorest and those living furthest away from a hospital are most affected. But the relative contribution of poverty and travel time is convoluted, since hospitals are often located in wealthier urban places and are scarcer in poorer remote area. This study aims to partition the variability in hospital-based childbirth by poverty and travel time in four sub-Saharan African countries.

Methods

We used data from the most recent Demographic and Health Survey in Kenya, Malawi, Nigeria and Tanzania. For each country, geographic coordinates of survey clusters, the master list of hospital locations and a high-resolution map of land surface friction were used to estimate travel time from each DHS cluster to the nearest hospital with a shortest-path algorithm. We quantified and compared the predicted probabilities of hospital-based childbirth resulting from one standard deviation (SD) change around the mean for different model predictors.

Results

The mean travel time to the nearest hospital, in minutes, was 27 (Kenya), 31 (Malawi), 25 (Nigeria) and 62 (Tanzania). In Kenya, a change of 1SD in wealth led to a 33.2 percentage points change in the probability of hospital birth, whereas a 1SD change in travel time led to a change of 16.6 percentage points. The marginal effect of 1SD change in wealth was weaker than that of travel time in Malawi (13.1 vs. 34.0 percentage points) and Tanzania (20.4 vs. 33.7 percentage points). In Nigeria, the two were similar (22.3 vs. 24.8 percentage points) but their additive effect was twice stronger (44.6 percentage points) than the separate effects. Random effects from survey clusters also explained substantial variability in hospital-based childbirth in all countries, indicating other unobserved local factors at play.

Conclusions

Both poverty and long travel time are important determinants of hospital birth, although they vary in the extent to which they influence whether women give birth in a hospital within and across countries. This suggests that different strategies are needed to effectively enable poor women and women living in remote areas to gain access to skilled and adequate care for childbirth.
How does lymph node yield affect survival outcomes of stage I and II colon cancer?
Authors: Foo Chi Chung , Ku Clement , Wei Rockson , Yip Jeremy , Tsang Julian , Chan Toi Yin , Lo Oswens , Law Wai Lun
Published: January 2020

Background

According to the American Joint Committee on Cancer staging for cancer of the colon, a minimum of 12 lymph nodes (LN) has to be sampled for accurate staging. This has bearing on the long-term prognosis and the need for adjuvant chemotherapy. The aim of this study was to revisit the association of lymph node yield and the long-term survival in patients with stages I and II, i.e. node-negative, colon cancer.

Method

Consecutive patients who underwent elective or emergency curative resections for cancer of colon between the years 2003 and 2012 were retrospectively reviewed. Only patients with stage I or II diseases (AJCC 8th edition) were included. They were analysed in three groups, LN<12, LN12-19 and LN≥20. Their clinic-pathological characteristics were compared. The disease-free (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test.

Results

There was a total of 659 patients included in the analysis. Twelve or more LN were found in 65.6% of the specimens. The mean follow-up was 83.9 months. LN≥20 had significantly better DFS (p = 0.015) and OS (p = 0.036), whereas LN<12 had similar DFS and OS when compared to LN12-19. The advantage in DFS and OS were mainly seen in those with stage II diseases. A lymph node yield of greater than 20 was one of the predictors of favourable DFS, hazard ratio 0.358; 95% CI 0.170–.756, p = 0.007.

Conclusion

The lymph node yield had a significant association with survival outcomes. A lymph node yield of 20 or more was associated with better survival outcomes. On the other hand, lymph node yield less than 12 was not shown to have inferior survival outcomes when compared to those between 12 and 19.
Expanding the mutational spectrum of monogenic hypogonadotropic hypogonadism: novel mutations in ANOS1 and FGFR1 genes
Authors: Gach Agnieszka , Pinkier Iwona , Szarras-Czapnik Maria , Sakowicz Agata , Jakubowski Lucjusz
Published: January 2020

Background

Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defective GnRH secretion, that is usually diagnosed in late adolescence or early adulthood due to the lack of spontaneous pubertal development. To date more than 30 genes have been associated with CHH pathogenesis with X-linked recessive, autosomal dominant, autosomal recessive and oligogenic modes of inheritance. Defective sense of smell is present in about 50–60% of CHH patients and called Kallmann syndrome (KS), in contrast to patients with normal sense of smell referred to as normosmic CHH.

ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH and have been extensively studied in many reported cohorts. Due to rarity and heterogenicity of the condition the mutational spectrum, even in classical CHH genes, have yet to be fully characterized.

Methods

To address this issue we screened for ANOS1 and FGFR1 variants in a cohort of 47 unrelated CHH subjects using targeted panel sequencing. All potentially pathogenic variants have been validated with Sanger sequencing.

Results

Sequencing revealed two ANOS1 and four FGFR1 mutations in six subjects, of which five are novel and one had been previously reported in CHH. Novel variants include a single base pair deletion c.313delT in exon 3 of ANOS1, three missense variants of FGFR1 predicted to result in the single amino acid substitutions c.331C > T (p.R111C), c.1964 T > C (p.L655P) and c.2167G > A (p.E723K) and a 15 bp deletion c.374_388delTGCCCGCAGACTCCG in exon 4 of FGFR1. Based on ACMG–AMP criteria reported variants were assigned to class 5, pathogenic or class 4, likely pathogenic. Protein structural predictions, the rarity of novel variants and amino acid conservation in case of missense substitutions all provide strong evidence that these mutations are highly likely to be deleterious.

Conclusions

Despite the fact that ANOS1 and FGFR1 are classical CHH genes and were thoroughly explored in several CHH cohorts we identified new, yet undescribed variants within their sequence. Our results support the genetic complexity of the disorder. The knowledge of the full genetic spectrum of CHH is increasingly important in order to be able to deliver the best personalised medical care to our patients.
Dental school tracks related to the retention of dentists in Thai government service: a cross-sectional survey
Authors: Vivatbutsiri Philaiporn , Iempook Thanachok , Wonghinkong Sakda , Sopa Sunisa , Detsomboonrat Palinee
Published: January 2020

Background

The shortage of dentists working in rural hospitals is an important public health problem resulting from dentist distribution inequity. The Ministry of Public Health of Thailand (MoPH) has implemented a policy of recruiting students with a rural background to be dental students and return home after graduating. This study aims to examine the relationship between admission tracks during the academic years 2005–2011 on retaining dentists in Thai government service and identify the factors associated with retention and resignation.

Methods

A cross-sectional survey was conducted using an online questionnaire from 287 dentists who graduated from Chulalongkorn University (CU) between 2010 and 2016. Follow-up data consisted of the admission track, number of years spent in Thai government service, and factors that influenced their decision to stay or resign from Thai government service. Chi-squared analysis was used to analyze the data.

Results

The overall retention rate in Thai government service was 58.2%. Dentists in the rural track had a significantly higher retention rate than the normal track (p = 0.023). Female dentists who were married and graduated less than 3 years had a significantly higher resignation rate than others (p < 0.05). The main reasons for retention were “security in the profession,” “high chance to pursue specialty training in the future,” and “close proximity to hometown.” Dentists from the CU rural admission tracks chose “close proximity to hometown” as the top reason, while others selected “security in the profession.” The main reasons influencing resignation were “workplace far away from hometown” and “getting specialty training.”

Conclusions

These results indicate that dentists in the rural track had a significantly higher retention rate than the normal track. The most important factor influencing both retention and resignation was workplace location, where being near to their hometown improved the retention rate of rural dentists. Therefore, the MoPH should increase student admission into the rural track to resolve the inequity in dentist distribution.
Health workforce demography: a framework to improve understanding of the health workforce and support achievement of the Sustainable Development Goals
Authors: Szabo Sylvia , Nove Andrea , Matthews Zoë , Bajracharya Ashish , Dhillon Ibadat , Singh Devendra Raj , Saares Aurora , Campbell James
Published: January 2020

The ambition of universal health coverage entails estimation of the number, type and distribution of health workers required to meet the population need for health services. The demography of the population, including anticipated or estimated changes, is a factor in determining the ‘universal’ needs for health and well-being. Demography is concerned with the size, breakdown, age and gender structure and dynamics of a population. The same science, and its robust methodologies, is equally applicable to the demography of the health workforce itself. For example, a large percentage of the workforce close to retirement will impact availability, a geographically mobile workforce has implications for health coverage, and gender distribution in occupations may have implications for workforce acceptability and equity of opportunity. In a world with an overall shortage of health workers, and the expectation of increasing need as a result of both population growth in the global south and population ageing in the global north, studying and understanding demographic characteristics of the workforce can help with future planning. This paper discusses the dimensions of health worker demography and considers how demographic tools and techniques can be applied to the analysis of the health labour market. A conceptual framework is introduced as a step towards the application of demographic principles and techniques to health workforce analysis and planning exercises as countries work towards universal health coverage, the reduction of inequities and national development targets. Some illustrative data from Nepal and Finland are shown to illustrate the potential of this framework as a simple and effective contribution to health workforce planning.
Lycopene and bone: an in vitro investigation and a pilot prospective clinical study
Authors: Russo Cristina , Ferro Yvelise , Maurotti Samantha , Salvati Maria Antonietta , Mazza Elisa , Pujia Roberta , Terracciano Rosa , Maggisano Giuseppina , Mare Rosario , Giannini Sandro , Romeo Stefano , Pujia Arturo , Montalcini Tiziana
Published: January 2020

Background

There are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.

Methods

We investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.

Results

Lycopene 10 µM resulted in higher β-catenin and phERK1/2 proteinVsthe vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p < 0.05). A significant bone density loss was not detected in women taking the tomato sauce while the control group had bone loss (p = 0.002). Tomato sauce intake resulted in a greater bone alkaline phosphatase reduction than the control (18% vs 8.5%, p = 0.03).

Conclusions

Lycopene activates the WNT/β-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.
Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring
Authors: Emam Baharan , Shahsavani Abbas , Khodagholi Fariba , Zarandi Saeed Motesaddi , Hopke Philip K. , Hadei Mostafa , Behbahani Hamidreza , Yarahmadi Maryam
Published: January 2020

Background

Epidemiological studies have reported associations between elevated air pollution and autism spectrum disorders (ASD). However, we hypothesized that exposure to air pollution that mimics real world scenarios, is a potential contributor to ASD. The exact etiology and molecular mechanisms underlying ASD are not well understood. Thus, we assessed whether changes in OXTR levels may be part of the mechanism linking PM2.5/gaseous pollutant exposure and ASD. The current in-vivo study investigated the effect of exposure to fine particulate matter (PM2.5) and gaseous pollutants on ASD using behavioral and molecular experiments. Four exposure groups of Wistar rats were included in this study: 1) particulate matter and gaseous pollutants exposed (PGE), 2) gaseous pollutants only exposed (GE), 3) autism-like model (ALM) with VPA induction, and 4) clean air exposed (CAE) as the control. Pregnant dams and male pups were exposed to air pollutants from embryonic day (E0) to postnatal day (PND21).

Results

The average ± SD concentrations of air pollutants were: PM2.5: 43.8 ± 21.1 μg/m3, CO: 13.5 ± 2.5 ppm, NO2: 0.341 ± 0.100 ppm, SO2: 0.275 ± 0.07 ppm, and O3: 0.135 ± 0.01 ppm. The OXTR protein level, catalase activity (CAT), and GSH concentrations in the ALM, PGE, and GE rats were lower than those in control group (CAE). However, the decrements in the GE rats were smaller than other groups. Also in behavioral assessments, the ALM, PGE, and GE rats demonstrated a repetitive /restricted behavior and poor social interaction, but the GE rats had weaker responses compared to other groups of rats. The PGE and GE rats showed similar trends in these tests compared to the VPA rats.

Conclusions

This study suggested that exposure to ambient air pollution contributed to ASD and that OXTR protein may serve as part of the mechanism linking them.