bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping with access barriers to non‐communicable disease medicines: qualitative patient interviews in eight counties in Kenya
Authors: Ng Gloria , Raskin Elizabeth , Wirtz Veronika J. , Banks Kathleen P. , Laing Richard O. , Kiragu Zana W. , Rockers Peter C. , Onyango Monica A.
Published: May 2021

Background

There is rich literature on barriers to medicines access for the treatment of non-communicable diseases (NCDs) in high-income countries. Less is known about low- and middle-income countries, in particular the differences in coping with medicines access barrier by household wealth and disease. The aim of this study was to compare the coping mechanisms of patients with the lack of availability and affordability of cardio-vascular diseases, diabetes and asthma medicines in Kenya.

Methods

This qualitative study was part of a larger mixed methods evaluation study conducted in eight counties of Kenya from 2016 to 2019. Forty-nine patient interviews at study end line explored their NCD journey, perceptions of availability, stockouts and affordability of NCD medicines, their enrollment in health insurance, and their relationship with the private chemists. Transcribed interviews were coded using Nvivo software. A two-step thematic approach was used, first conducting a priority coding which was followed by coding emerging and divergent themes.

Results

Overall, we found that patients across all disease types and wealth level faced frequent medicine stock-outs at health facilities. In the absence of NCD medicines at health facilities, patients coped by purchasing medicines from local chemists, switching health facilities, requesting a different prescription, admitting oneself to an inpatient facility, establishing connections with local staff to receive notifications of medicine stock, stocking up on medicines, utilizing social capital to retrieve medicines from larger cities and obtaining funds from a network of friends and family. Categorizing by disease revealed patterns in coping choices that were based on the course of the disease, severity of the symptoms and the direct and indirect costs incurred as a result of stockouts of NCD medicines. Categorizing by wealth highlight differences in households’ capacity to cope with the unavailability and unaffordability of NCD medicines.

Conclusions

The type of coping strategies to access barriers differ by NCD and wealth group. Although Kenya has made important strides to address NCD medicines access challenges, prioritizing enrollment of low wealth households in county health insurance programs and ensuring continuous availability of essential NCD medicines at public health facilities close to the patient homes could improve access.
Examining non-medical prescribing trends in New Zealand: 2016–2020
Authors: Raghunandan Rakhee , Marra Carlo A. , Tordoff June , Smith Alesha
Published: May 2021

Background

Population growth and general practitioner workforce constraints are creating increasing demand for health services in New Zealand (NZ) and internationally. Non-medical prescribing (NMP) is one strategy that has been introduced to help manage this. Little is known about the NMP practice trends in NZ. The aim of this study was to provide a current overview of the scale, scope, and trends of NMP practice in NZ.

Methods

All claims for community dispensed medicines prescribed by a non-medical prescriber were extracted from the NZ Pharmaceutical Collection for the period 2016–2020. Patient demographics were retrieved from the Primary Health Organisation enrolment collection. These national databases contain prescription information for all subsidised community pharmacy medicines dispensed and healthcare enrolment data for 96% of New Zealanders.

Results

The proportion of prescriptions written by all NMP providers and patients receiving NMP prescriptions increased each year from 1.8% (2016) to 3.6% (2019) and 8.4% (2016) to 14.4% (2019) respectively. From 2016 to 2019, the proportion of NMP patients who had at least one NMP prescription increased from 26% to 39% for nurse prescribers, from 1% to 9% for pharmacist prescribers, from 2% to 3% for dietitian prescribers, and decreased from 47% to 22% for dentists, and from 20% to 12% for midwives. The most commonly prescribed medicines were antibiotics (amoxicillin, amoxicillin with clavulanic acid, and metronidazole), and analgesics (paracetamol, and codeine phosphate). While some NMP providers were prescribing for patients with greater health needs, all NMP providers could be better utilised to reach more of these patients.

Conclusions

This study highlights that although the NMP service has been implemented in NZ, it has yet to become mainstream healthcare practice. This work provides a baseline to evaluate the NMP service moving forward and enable policy development. Improved implementation and integration of primary care NMP services can ensure continued access to prescribing services and medicines for our communities.
Impact of male trait exaggeration on sex-biased gene expression and genome architecture in a water strider
Authors: Toubiana William , Armisén David , Dechaud Corentin , Arbore Roberto , Khila Abderrahman
Published: April 2021

Background

Exaggerated secondary sexual traits are widespread in nature and often evolve under strong directional sexual selection. Although heavily studied from both theoretical and empirical viewpoints, we have little understanding of how sexual selection influences sex-biased gene regulation during the development of exaggerated secondary sexual phenotypes, and how these changes are reflected in genomic architecture. This is primarily due to the limited availability of representative genomes and associated tissue and sex transcriptomes to study the development of these traits. Here we present the genome and developmental transcriptomes, focused on the legs, of the water strider Microvelia longipes, a species where males exhibit strikingly long third legs compared to females, which they use as weapons.

Results

We generated a high-quality genome assembly with 90% of the sequence captured in 13 scaffolds. The most exaggerated legs in males were particularly enriched in both sex-biased and leg-biased genes, indicating a specific signature of gene expression in association with trait exaggeration. We also found that male-biased genes showed patterns of fast evolution compared to non-biased and female-biased genes, indicative of directional or relaxed purifying selection. By contrast to male-biased genes, female-biased genes that are expressed in the third legs, but not the other legs, are over-represented in the X chromosome compared to the autosomes. An enrichment analysis for sex-biased genes along the chromosomes revealed also that they arrange in large genomic regions or in small clusters of two to four consecutive genes. The number and expression of these enriched regions were often associated with the exaggerated legs of males, suggesting a pattern of common regulation through genomic proximity in association with trait exaggeration.

Conclusion

Our findings indicate how directional sexual selection may drive sex-biased gene expression and genome architecture along the path to trait exaggeration and sexual dimorphism.
Sensory adaptations reshaped intrinsic factors underlying morphological diversification in bats
Authors: Arbour J. H. , Curtis A. A. , Santana S. E.
Published: April 2021

Background

Morphological evolution may be impacted by both intrinsic (developmental, constructional, physiological) and extrinsic (ecological opportunity and release) factors, but can intrinsic factors be altered by adaptive evolution and, if so, do they constrain or facilitate the subsequent diversification of biological form? Bats underwent deep adaptive divergences in skull shape as they evolved different sensory modes; here we investigate the potential impact of this process on two intrinsic factors that underlie morphological variation across organisms, allometry, and modularity.

Results

We use comparative phylogenetic and morphometric approaches to examine patterns of evolutionary allometry and modularity across a 3D geometric morphometric dataset spanning all major bat clades. We show that allometric relationships diverge between echolocators and visually oriented non-echolocators and that the evolution of nasal echolocation reshaped the modularity of the bat cranium.

Conclusions

Shifts in allometry and modularity may have significant consequences on the diversification of anatomical structures, as observed in the bat skull.
Evaluation of digital thermography imaging to assess and monitor treatment of police working dogs with naturally occurring hip osteoarthritis
Authors: Alves J. C. , Santos A. , Jorge P. , Lavrador C. , Carreira L. Miguel
Published: May 2021

Background

In dogs, thermal imaging has been documented only recently, but a growing interest in this modality has led to studies using thermography to assess pathologies in the canine hip, stifle, elbow, intervertebral disc, and bone neoplasia. This study aimed to evaluate the use of digital thermography in assessing and evaluating treatment response in dogs with hip osteoarthritis (OA) and comparing its results with an objective measure and two clinical metrology instruments. In an experimental, randomized, double-blinded study, one hundred hip joints of fifty police working dogs with bilateral hip OA were evaluated. A dorsoventral and lateral thermographic image were obtained on days 0, 8, 15, 30, 90, and 180. Mean and maximal temperatures were determined. Additionally, the animal’s weight-bearing distribution and radiographic examination of the hip joint (extended legs ventrodorsal view) were performed. Copies of the Canine Brief Pain Inventory (CBPI) and Canine Orthopaedic Index (COI) were obtained. Results were analyzed by ANOVA, followed by an LSD post-hoc test, and correlations were assessed with Spearman correlation coefficient, with p < 0.05.

Results

Values recorded on the lateral view were higher than those on the dorsoventral view. No differences or correlations were found between Orthopedic Foundation for Animals hip grades and temperature. Digital thermographic images showed a weak significant correlation with weight-bearing evaluations (r = 0.13, p < 0.01) and different clinical metrology instruments scores (r = − 0.25, p < 0.01 for pain severity score, and r = − 0.21, p = 0.04 for gait). It also correlated with radiographic findings, specifically the circumferential femoral head osteophyte and caudolateral curvilinear osteophyte.

Conclusion

To our knowledge, this is the first study presenting the digital thermography assessment of Police working dogs submitted to treatment for hip OA. Digital thermography, mainly based on a lateral view evaluation, showed a weak significant correlation with stance analysis and clinical metrology instruments scores.
Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection
Authors: Malgarin Carolina M. , Moser Fiona , Pasternak J. Alex , Hamonic Glenn , Detmer Susan E. , MacPhee Daniel J. , Harding John C. S.
Published: May 2021

Background

Mechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC).

Results

In experiment 1, paraffin embedded fetal tissues collected 21 days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses.

Conclusions

There is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.
qPCR assays with dual-labeled probes for genotyping honey bee variants associated with varroa resistance
Authors: Claeys Boúúaert David , Van Poucke Mario , De Smet Lina , Verbeke Wim , de Graaf Dirk C. , Peelman Luc
Published: April 2021

Background

The varroa mite is one of the main causes of honey bee mortality. An important mechanism by which honey bees increase their resistance against this mite is the expression of suppressed mite reproduction. This trait describes the physiological inability of mites to produce viable offspring and was found associated with eight genomic variants in previous research.

Results

This paper presents the development and validation of high-throughput qPCR assays with dual-labeled probes for discriminating these eight single-nucleotide variants. Amplicon sequences used for assay validation revealed additional variants in the primer/probe binding sites in four out of the eight assays. As for two of these the additional variants interfered with the genotyping outcome supplementary primers and/or probes were developed. Inclusion of these primers and probes in the assay mixes allowed for the correct genotyping of all eight variants of interest within our bee population.

Conclusion

These outcomes underline the importance of checking for interfering variants in designing qPCR assays. Ultimately, the availability of this assay allows genotyping for the suppressed mite reproduction trait and paves the way for marker assisted selection in breeding programs.
Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON
Authors: Lorenzatti Alberto J. , Monsalvo Maria Laura , López J. Antonio G. , Wang Huei , Rosenson Robert S.
Published: May 2021

Background

Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM.

Methods

This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD.

Results

In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12.

Conclusions

Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.
Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma
Authors: Weinman Marcus A. , Ramsey Stephen A. , Leeper Haley J. , Brady Jacqueline V. , Schlueter Andrew , Stanisheuski Stanislau , Maier Claudia S. , Miller Tasha , Ruby Carl E. , Bracha Shay
Published: May 2021

Background

Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized.

Methods

In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy.

Results

Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of > 300 days, and dogs with < 100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient’s exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared.

Conclusions

The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.
Knockdown of MCM8 inhibits development and progression of bladder cancer in vitro and in vivo
Authors: Zhu Wei , Gao Fei , Zhou Hongyi , Jin Ke , Shao Jianfeng , Xu Zhuoqun
Published: April 2021

Background

Bladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Unfortunately, little is known concerning the roles of MCM8 in bladder cancer.

Methods

The present study, we aimed at probing into the impacts and detailed mechanisms of MCM8 in bladder cancer progression. In this study, MCM8 expression level was detected through immunohistochemistry staining (IHC), qRT-PCR and Western blot assay. Silenced MCM8 cell models were constructed by lentivirus transfection. In vitro, the cell proliferation was evaluated by the MTT assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were determined by flow cytometry. Moreover, the Human Apoptosis Antibody Array assay was performed to analyze the alterations of apoptosis-related proteins. The in vivo experiments were conducted to verify the effects of MCM8 knockdown on the tumor growth of bladder cancer.

Results

The results demonstrated that compared with normal adjacent tissues, MCM8 expression in bladder cancer tissues was strongly up-regulated. The up-regulation of MCM8 expression in bladder cancer may be a valuable independent prognostic indicator. Of note, MCM8 inhibition modulated the malignant phenotypes of bladder cancer cells. In terms of mechanism, it was validated that MCM8 knockdown made Akt, P-Akt, CCND1 and CDK6 levels down-regulated, as well as MAPK9 up-regulated.

Conclusions

Taken together, our study demonstrated an important role of MCM8 in bladder cancer and created a rationale for the therapeutic potential of MCM8 inhibition in human bladder cancer therapy.
Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer
Authors: Cui Yuxin , Li Liting , Li Zhilei , Yin Jie , Lane Jane , Ji Jiafu , Jiang Wen G.
Published: April 2021

Background

S100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised.

Methods

Transcript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer.

Results

High expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin.

Conclusion

The present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.
Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017
Authors: Rouamba Toussaint , Samadoulougou Sékou , Ouédraogo Mady , Hien Hervé , Tinto Halidou , Kirakoya-Samadoulougou Fati
Published: May 2021

Background

Malaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level.

Methods

Data of 1751 pregnant women from October 2013 to March 2014 and 1931 pregnant women from April 2017 to June 2017 were drawn from two cross-sectional household surveys conducted in 24 health districts of Burkina Faso. Pregnant women were tested for malaria in their household after consenting. Asymptomatic carriage was defined as a positive result from malaria rapid diagnostic tests in the absence of clinical symptoms of malaria. Anaemia was defined as haemoglobin level less than 11 g/dL in the first and third trimester and less than 10.5 g/dL in the second trimester of pregnancy.

Results

Prevalence of asymptomatic malaria in pregnancy was estimated at 23.9% (95% CI 20.2–28.0) during the high transmission season (October–November) in 2013. During the low transmission season, it was 12.7% (95% CI 10.9–14.7) between December and March in 2013–2014 and halved (6.4%; 95% CI 5.3–7.6) between April and June 2017. Anaemia prevalence was estimated at 59.4% (95% CI 54.8–63.8) during the high transmission season in 2013. During the low transmission season, it was 50.6% (95% CI 47.7–53.4) between December and March 2013–2014 and 65.0% (95% CI 62.8–67.2) between April and June, 2017.

Conclusion

This study revealed that the prevalence of malaria asymptomatic carriage and anaemia among pregnant women at the community level remain high throughout the year. Thus, more efforts are needed to increase prevention measures such as IPTp–SP coverage in order to reduce anaemia and contribute to preventing low birth weight and poor pregnancy outcomes.
Molecular surveillance of anti-malarial resistance pfcrt, pfmdr1, and pfk13 polymorphisms in African Plasmodium falciparum imported parasites to Wuhan, China
Authors: Cheng Weijia , Song Xiaonan , Tan Huabing , Wu Kai , Li Jian
Published: May 2021

Background

Imported malaria parasites with anti-malarial drug resistance (ADR) from Africa is a serious public health challenge in non-malarial regions, including Wuhan, China. It is crucial to assess the ADR status in African Plasmodium falciparum isolates from imported malaria cases, as this will provide valuable information for rational medication and malaria control.

Methods

During 2017–2019, a cross-sectional study was carried out in Wuhan, China. Peripheral blood 3 ml of returned migrant workers from Africa was collected. The target fragments from pfcrt, pfmdr1, and k13 propeller (pfk13) genes were amplified, sequenced, and analysed.

Results

In total, 106 samples were collected. Subsequently, 98.11% (104/106), 100% (106/106), and 86.79% (92/106) of these samples were successfully amplified and sequenced for the pfcrt (72–76), pfmdr1, and pfk13 genes, respectively. The prevalence of the pfcrt 76 T, pfmdr1 86Y, and pfmdr1 184F mutations was 9.62, 4.72, and 47.17%, respectively. At codons 72–76, the pfcrt locus displayed three haplotypes, CVMNK (wild-type), CVIET (mutation type), CV M/I N/E K/T (mixed type), with 87.50%, 9.62%, and 2.88% prevalence, respectively. For the pfmdr1 gene, NY (wild type), NF and YF (mutant type), N Y/F, Y Y/F, and N/Y Y/F (mixed type) accounted for 34.91, 43.40, 3.77, 15.09, 0.94, and 1.89% of the haplotypes, respectively. A total of 83 isolates with six unique haplotypes were found in pfcrt and pfmdr1 combined haplotypes, of which NY-CVMNK and NF-CVMNK accounted for 40.96% (34/83) and 43.37% (36/83), respectively. Furthermore, 90 cases were successfully sequenced (84.91%, 90/106) at loci 93, 97, 101, and 145, and 78 cases were successfully sequenced (73.58%, 78/106) at loci 343, 353, and 356 for pfcrt. However, the mutation was observed only in locus 356 with 6.41%. For pfk13, mutations reported in Southeast Asia (at loci 474, 476, 493, 508, 527, 533, 537, 539, 543, 553, 568, 574, 578, and 580) and Africa (at loci 550, 561, 575, 579, and 589) were not observed.

Conclusions

The present data from pfcrt and pfmdr1 demonstrate that anti-malarial drugs including chloroquine, amodiaquine, and mefloquine, remain effective against malaria treatment in Africa. The new mutations in pfcrt related to piperaquine resistance remain at relatively low levels. Another source of concern is the artemether-lumefantrine resistance-related profiles of N86 and 184F of pfmdr1. Although no mutation in pfk13 is detected, molecular surveillance must continue.
A multi-center longitudinal study on responsive breastfeeding in China from the perspective of health equity: research protocol
Authors: Shu Wen , Li Menglong , Amaerjiang Nubiya , Fan Xin , Lin Shunna , Segura-Pérez Sofia , Pérez-Escamilla Rafael , Hu Yifei
Published: May 2021

Background

Socio-economic inequities can strongly influence suboptimal infant feeding outcomes. Factors such as lack of knowledge about breastfeeding, low family income, low educational attainment, social and economic status, cultural norms and ethnicity may negatively affect success with offering breastfeeding following a responsive feeding approach (ie. responsive breastfeeding). Such inequities can indeed shorten breastfeeding duration, and negatively affect behavioral and cognitive infant outcomes. In China, there is a dearth of studies focusing on breastfeeding from the responsive and health equity perspective.

Objective

The aim of this article is to present a protocol of an ongoing longitudinal cohort study investigating factors associated with responsive breastfeeding behaviors, and the child’s behavioral and cognitive development from birth to12 months post-partum in five centers in China. The study seeks to identify breastfeeding barriers and facilitators from a health equity perspective.

Methods

We are enrolling 700 women and their singleton full term infants in Chongqing, Huizhou and Guangzhou urban and rural areas. The study questionnaires will be administrated within 72 h, 30 days, 3, 6, 9, and 12 months post-partum during the baby’s vaccination visits. We will investigate the difference between urban and rural areas sociodemographic characteristics, breastfeeding knowledge, attitudes and practice, postnatal depression, maternal emotion regulation and parenting stress, and anthropometric and cognitive development indicators of the infants at each time-point.

Conclusion

Our article illustrates how a cohort study can be designed to understand the barriers and facilitators of responsive breastfeeding taking equity principles into account to help promote infants’ growth and development in China.
Innovations in the national household random sampling in Brazilian National Health Survey: results from Starfield and Shi’s adult primary care assessment tool (PCAT)
Authors: Pinto Luiz Felipe , D’Avila Otavio Pereira , Hauser Lisiane , Harzheim Erno
Published: May 2021

Background

Several middle and upper income countries carry out household surveys that seek to trace the profile of access and use of health services. Probably one of the most ambitious examples is Brazil, with its National Health Survey (PNS-2019). We evaluated PNS-2019, presenting in an unprecedented way, one of its innovations, which refer to Starfield and Shi’s adult Primary Care Assessment Tool (PCAT).

Methods

Based on a cross-sectional study, we evaluated Module H of the PNS-2019, which interviewed a probabilistic sample of about 10,000 adults in 2019 in all 27 Brazilian states. According to the PCAT methodology, an average score equal to or above 6.6 indicates a greater orientation and quality of the evaluated primary care services.

Results

Brazilian overall PCAT score [5, 9] reveals the need to improve primary health care services across the country. There were no statistically significant differences in the scores by sex (men and women, 5.9), and race (whites 5.9 [5.7; 6.0] and brown / black 5.9 [5.8; 6.0]). On the other hand, there was a difference in terms of age. The elderly evaluated the services in a more positive way (score = 6.1 [6.0; 6.2]), when compared to those aged 40–59 years (5.9 [5.7; 6.0]) and 18 to 39 years (5.6 [5.5; 5.8]). First results of PNS-2019 show that the population that most needs primary care services in SUS is the one with the best perception and the most positive evaluation of the actions and procedures offered in health facilities.

Discussion

During 2019, Brazil undertook important structural reforms in PHC based on a new financing model with the aim of inducing an improvement in efficiency and strengthening its attributes. It is essential that countries with universal health coverage (UHC) guarantee access to their population and, especially, the most vulnerable, seek better efficiency of these services and regularly assess PHC based on the population’s perception, through an independent methodology that monitor the quality of services and the strength of PHC, generating value for public resources applied to health services.
Feelings of safety during daytime walking: associations with mental health, physical activity and cardiometabolic health in high vacancy, low-income neighborhoods in Detroit, Michigan
Authors: Pearson Amber L. , Clevenger Kimberly A. , Horton Teresa H. , Gardiner Joseph C. , Asana Ventra , Dougherty Benjamin V. , Pfeiffer Karin A.
Published: May 2021

Introduction

Individuals living in low-income neighborhoods have disproportionately high rates of obesity, Type-2 diabetes, and cardiometabolic conditions. Perceived safety in one’s neighborhood may influence stress and physical activity, with cascading effects on cardiometabolic health.

Methods

In this study, we examined relationships among feelings of safety while walking during the day and mental health [perceived stress (PSS), depression score], moderate-to-vigorous physical activity (PA), Body Mass Index (BMI), and hemoglobin A1C (A1C) in low-income, high-vacancy neighborhoods in Detroit, Michigan. We recruited 69 adults who wore accelerometers for one week and completed a survey on demographics, mental health, and neighborhood perceptions. Anthropometrics were collected and A1C was measured using A1CNow test strips. We compiled spatial data on vacant buildings and lots across the city. We fitted conventional and multilevel regression models to predict each outcome, using perceived safety during daytime walking as the independent variable of interest and individual or both individual and neighborhood-level covariates (e.g., number of vacant lots). Last, we examined trends in neighborhood features according to perceived safety.

Results

In this predominantly African American sample (91%), 47% felt unsafe during daytime walking. Feelings of perceived safety significantly predicted PSS (β = − 2.34, p = 0.017), depression scores (β = − 4.22, p = 0.006), and BMI (β = − 2.87, p = 0.01), after full adjustment. For PA, we detected a significant association for sex only. For A1C we detected significant associations with blighted lots near the home. Those feeling unsafe lived in neighborhoods with higher park area and number of blighted lots.

Conclusion

Future research is needed to assess a critical pathway through which neighborhood features, including vacant or poor-quality green spaces, may affect obesity—via stress reduction and concomitant effects on cardiometabolic health.
Paradigm shift: the primary function of the “Adiponectin Receptors” is to regulate cell membrane composition
Authors: Pilon Marc
Published: April 2021

The ADIPOR1 and ADIPOR2 proteins (ADIPORs) are generally considered as adiponectin receptors with anti-diabetic properties. However, studies on the yeast and C. elegans homologs of the mammalian ADIPORs, and of the ADIPORs themselves in various mammalian cell models, support an updated/different view. Based on findings in these experimental models, the ADIPORs are now emerging as evolutionarily conserved regulators of membrane homeostasis that do not require adiponectin to act as membrane fluidity sensors and regulate phospholipid composition. More specifically, membrane rigidification activates ADIPOR signaling to promote fatty acid desaturation and incorporation of polyunsaturated fatty acids into membrane phospholipids until fluidity is restored. The present review summarizes the evidence supporting this new view of the ADIPORs, and briefly examines physiological consequences.
Influence of uric acid on the correlation between waist circumference and triglyceride glucose index: an analysis from CHARLS
Authors: Zheng Jia , Jiang Min , Xie Yanxia
Published: April 2021

Background

Waist circumference (WC) and uric acid (UA) are significantly related. Still, their temporal sequence and how the sequence works on future risk of triglyceride glucose (TyG) are unknown, especially in the Chinese population.

Methods

Cross-lagged panel model was used to analyze the reciprocal, longitudinal relationships among a set of interrelated variables. The mediation model was constructed to test the effect of the relationship between WC and UA on TyG.

Results

A total of 5727 subjects were enrolled in our study population, of which 53.5% were women, and the mean age was 59.0 (standard deviation, 8.62) years. After adjusting for traditional confounding factors, the results showed that a higher level of baseline WC was significantly associated with a higher level of follow-up UA (β = 0.003, P = 0.031) and follow-up TyG (β = 0.003, P < 0.001);. Simultaneously, there was no statistical association between the level of baseline UA and the level of follow-up WC (β = − 0.009, P = 0.951). The mediation effects of UA on WC-TyG were estimated to be 18.1% in adults, and 36.2% in women.

Conclusions

The current study demonstrated that higher baseline level of WC probably preceded UA’ level in general population. In addition, UA mediated the relationship of WC to TyG, especially in females. And the possible mechanism would require further clarification.
The extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau
Authors: Balmik Abhishek Ankur , Sonawane Shweta Kishor , Chinnathambi Subashchandrabose
Published: May 2021

Background

Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein.

Methods

Here, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization.

Results

HDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3β increases without any change in total GSK-3β level.

Conclusions

HDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.
Poorer mental health and sleep quality are associated with greater self-reported reward-related eating during pregnancy and postpartum: an observational cohort study
Authors: Betts Grace M. , Lipsky Leah M. , Temmen Chelsie D. , Siega-Riz Anna Maria , Faith Myles S. , Nansel Tonja R.
Published: May 2021

Background

Depression, stress, and poor-quality sleep are common during pregnancy and postpartum, but the relationship of these factors with reward-related eating is not well understood. This observational cohort study examines associations of depression, stress, and sleep quality with self-reported reward-related eating in pregnancy and postpartum.

Methods

Participants were enrolled at < 12 weeks gestation and followed through 1 year postpartum. Self-reported measures obtained at baseline and 23–31 weeks postpartum included the Edinburgh Postnatal Depression Scale, Perceived Stress Scale, Pittsburgh Sleep Quality Index; reward-related eating measures included the Power of Food Scale (assessing hedonic hunger), modified Yale Food Addiction Scale (assessing addictive-like eating), and frequency and intensity of cravings. Linear and logistic regression models estimated associations of depressive symptoms, stress, and sleep quality with reward-related eating during pregnancy and postpartum, as well as change in each predictor with change in outcome.

Results

During pregnancy, greater depressive symptoms (β ± SE = 0.03 ± 0.01, p < .01), higher stress (0.03 ± 0.01, p < .01), and worse sleep quality (0.03 ± 0.01, p = 0.03) were associated with greater hedonic hunger. Similarly, greater depressive symptoms (OR = 1.08, 95% CI: 1.02, 1.14, p = .01), higher stress (OR = 1.09, 95% CI: 1.04, 1.14, p = <.01), and worse sleep quality (OR = 1.09, 95% CI: 1.00, 1.18, p = .04) were associated with greater odds of addictive-like eating. These associations were also significant in postpartum except that sleep quality was not associated with hedonic hunger. Greater depressive symptoms (β ± SE = 0.06 ± 0.02, p < .01; 0.08 ± 0.02, p = <.01), higher stress (0.04 ± 0.01, p < .01; 0.06 ± 0.02, p < .01), and worse sleep quality (0.11 ± 0.03, p < .01; 0.13 ± 0.03, p < .01) during pregnancy were associated with stronger and more frequent cravings, respectively. Increased depressive symptoms from pregnancy to postpartum was associated with increased hedonic hunger (β ± SE = 1.17 ± 0.57, p = 0.01) and addictive-like eating (0.88 ± 0.33, p = 0.01), and increased stress was associated with increased hedonic hunger (1.71 ± 0.76, p = 0.02). Change in stress was not associated with change in addictive-like eating and change in sleep quality was not associated with change in either hedonic hunger or addictive-like eating.

Conclusions

Greater depressive symptoms, perceived stress, and poorer sleep quality are associated with greater self-reported reward-related eating during pregnancy and postpartum, suggesting that efforts to improve diet during and after pregnancy may benefit from addressing mental health and sleep.

Trial registration

Clinicaltrials.gov

Registration ID – NCT02217462.

Date of registration – August 13, 2014
Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway
Authors: Long Shiqi , Gu Yangzhuo , An Yuanyuan , Lin Xiaojin , Chen Xiaoqing , Wang Xianyao , Liao Chunxiang , Ouyang Weiwei , Wang Nianxue , He Zhixu , Zhao Xing
Published: May 2021

Background

Cetuximab has been approved for use for first-line treatment of patients with wild-type KRAS metastatic colorectal cancer (CRC). However, treatment with cetuximab has shown limited efficacy as a CRC monotherapy. In addition, natural killer (NK) cell function is known to be severely attenuated in cancer patients. The goal of this study was to develop a new strategy to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, in combination with cetuximab against CRC cells.

Methods

Ex vivo expanded NK cells were stimulated with reovirus, and reovirus-activated NK cells mediated ADCC assay were performed on CRC cells in combination with cetuximab. The synergistic antitumor effects of reovirus-activated NK cells and cetuximab were tested on DLD-1 tumor-bearing mice. Finally, Toll-like receptor 3 (TLR3) knockdown in NK cells, along with chemical blockade of TLR3/dsRNA complex, and inhibition of the TLR3 downstream signaling pathway, were performed to explore the mechanisms by which reovirus enhances NK cell cytotoxicity.

Results

We first confirmed that exposure of NK cells to reovirus enhanced their cytotoxicity in a dose-dependent manner.We then investigated whether reovirus-activated NK cells exposed to cetuximab-bound CRC cells exhibited greater anti-tumor efficacy than either monotherapy. Co-culture of CRC cell lines with reovirus-activated NK cells indicated that NK cytotoxicity was significantly higher in combination with cetuximab, regardless of KRAS mutation status or EGFR expression level. We also found that reovirus activation of NK cells, in conjunction with cetuximab, resulted in significantly stronger anti-tumor efficacy.Finally, TLR3 knockdown, inhibition of TLR3/dsRNA complex or TBK1/IKKε demonstrated that activation of NK cells by reovirus was dependent on TLR3 and its downstream signaling pathway.

Conclusions

This study demonstrated that combination treatment of reovirus-activated NK cells with cetuximab synergistically enhances their anti-tumor cytotoxicity, suggesting a strong candidate strategy for clinical treatment of CRC.
A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells is associated with acute hepatic rejection: a case control study
Authors: Zhu Ji-Qiao , Wang Jing , Li Xian-Liang , Xu Wen-Li , Lv Shao-cheng , Zhao Xin , Lang Ren , He Qiang
Published: May 2021

Background

T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker.

Methods

Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort.

Results

Upon activation the expression of TGF-β and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885–0.964; p = 0.000).

Conclusions

A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.