bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of diet and radiation on the bacterial symbiome of the melon fly, Zeugodacus cucurbitae (Coquillett)
Authors: Asimakis Elias D. , Khan Mahfuza , Stathopoulou Panagiota , Caceres Carlos , Bourtzis Kostas , Tsiamis George
Published: December 2019

Background

Symbiotic bacteria contribute to a multitude of important biological functions such as nutrition and reproduction and affect multiple physiological factors like fitness and longevity in their insect hosts. The melon fly,Zeugodacus cucurbitae(Coquillett), is an important agricultural pest that affects a variety of cultivated plants belonging mostly to the Cucurbitaceae family. It is considered invasive and widespread in many parts of the world. Several approaches are currently being considered for the management of its populations including the environmentally friendly and effective sterile insect technique (SIT), as a component of an integrated pest management (IPM) strategy. In the present study, we examined the effect of diet and radiation on the bacterial symbiome ofZ.cucurbitaeflies with the use of Next Generation Sequencing technologies.

Results

Melon flies were reared on two diets at the larval stage, an artificial bran-based diet and on sweet gourd, which affected significantly the development of the bacterial profiles. Significant differentiation was also observed based on gender. The effect of radiation was mostly diet dependent, with irradiated melon flies reared on the bran diet exhibiting a significant reduction in species diversity and richness compared to their non-irradiated controls. Changes in the bacterial symbiome of the irradiated melon flies included a drastic reduction in the number of sequences affiliated with members ofCitrobacter,Raoultella, and Enterobacteriaceae. At the same time, an increase was observed for members ofEnterobacter,ProvidenciaandMorganella. Interestingly, the irradiated male melon flies reared on sweet gourd showed a clear differentiation compared to their non-irradiated controls, namely a significant reduction in species richness and minor differences in the relative abundance for members ofEnterobacterandProvidencia.

Conclusions

The two diets in conjunction with the irradiation affected significantly the formation of the bacterial symbiome. Melon flies reared on the bran-based artificial diet displayed significant changes in the bacterial symbiome upon irradiation, in all aspects, including species richness, diversity and composition. When reared on sweet gourd, significant changes occurred to male samples due to radiation, only in terms of species richness.
A walk on the wild side: gut bacteria fed to mass-reared larvae of Queensland fruit fly [Bactrocera tryoni (Froggatt)] influence development
Authors: Shuttleworth Lucas Alexander , Khan Mohammed Abul Monjur , Osborne Terrence , Collins Damian , Srivastava Mukesh , Reynolds Olivia Louise
Published: December 2019

Background

The Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera, Tephritidae) is the most significant insect pest of Australian horticulture. Bactrocera tryoni is controlled using a range of tools including the Sterile Insect Technique (SIT). Mass-rearing and irradiation of pupae in SIT can reduce the fitness and quality of the released sterile insects. Studies have also showed reduced microbial gut diversity in domesticated versus wild tephritids.

Results

Transmission electron microscopy confirmed the presence of the bacterial isolates in the mid-gut of mass-reared larvae, and plate counts from individual larval guts showed increased numbers of bacteria in supplemented larvae. Several developmental and fitness parameters were tested including larval development time (egg-hatch to pupation), pupal weight, emergence, flight ability, sex-ratio, and time to adult eclosion (egg-hatch to adult eclosion). Enterobacter sp. and Asaia sp. shortened larval development time, while this was delayed by Lactobacillus sp., Leuconostoc sp. and a blend of all four bacteria. The mean time from egg hatch to adult eclosion was significantly reduced by Leuconostoc sp. and the blend for males and females, indicating that the individual bacterium and consortium affect flies differently depending on the life stage (larval or pupal). There was no impact of bacterial supplemented larvae on pupal weight, emergence, flight ability, or sex ratio.

Conclusions

Our findings show that bacteria fed to the larval stage of B. tryoni can impart fitness advantages, but the selection of probiotic strains (individual or a consortium) is key, as each have varying effects on the host. Bacteria added to the larval diet particularly Leuconostoc sp. and the blend have the capacity to reduce costs and increase the number of flies produced in mass-rearing facilities by reducing time to adult eclosion by 1.3 and 0.8 mean days for males, and 1.2 and 0.8 mean days for females.
The oesophageal diverticulum of Dirioxa pornia studied through micro-CT scan, dissection and SEM studies
Authors: Bhandari Kala , Crisp Peter , Keller Michael A.
Published: December 2019

Background

Dirioxa pornia (Diptera, Tephritidae) (Island fly) is an Australian native species related to a number of pestiferous fruit flies but, unlike many of the pest species, has not been studied extensively due to its non-pest status. However, due to D. pornia’s apparent reliance on the bacteria for survival it is an ideal species to undertake studies into interaction between Tephritid species and bacteria associated with the intestinal tract. The oesophageal diverticulum, which is a blind-ended protrusion of the oesophagus, has been studied, described and characterised in many other Tephritid species. Unlike many other species where the oesophageal diverticulum has been observed the organ was only observed in male D. pornia. It is speculated that this sexual dimorphism the organ may be the primary location to host beneficial bacteria in the involved in the production of the nuptial gift and the mating success of this Tephritid species. In case of D. pornia, however, no study on any area of the digestive system has been conducted. This study was conducted to locate and characterize the oesophageal diverticulum in D. pornia. A virtual dissection of the alimentary tract was made through micro-computer tomography studies. These studies were followed by dissection and scanning microscopy studies to elucidate the presence of bacteria.

Results

The oesophageal diverticulum of D. pornia is part of the foregut and distends from the oesophagus within the head of the fly. The shape of the oesophageal diverticulum corresponds with the Ceratitis type. Scanning microscopy studies of the oesophageal diverticulum show rod-shaped bacterial cells residing along with yeast cells in the lumen. The organ was only observed in male specimens.

Conclusions

This study classifies the oesophageal diverticulum of D. pornia under the “Ceratitis type” of oesophageal diverticula in Tephritid species. The study also proves that micro-CT scanning is possible to locate soft tissues in Tephritid species and the Avizo® Fire software can be successfully used to visualize 3 dimensional (3D) images from x-rays. The methods used in this experiment can be used in future studies for visualising soft tissues of adult Tephritid species through micro tomography. There is sexual dimorphism with the organ only found in males. Finally this study shows that bacteria are present in the oesophageal diverticulum of D. pornia.
Medfly-Wolbachia symbiosis: genotype x genotype interactions determine host’s life history traits under mass rearing conditions
Authors: Kyritsis Georgios A. , Augustinos Antonios A. , Livadaras Ioannis , Cáceres Carlos , Bourtzis Kostas , Papadopoulos Nikos T.
Published: December 2019

Background

Wolbachia pipientisis a widespread, obligatory intracellular and maternally inherited bacterium, that induces a wide range of reproductive alterations to its hosts. Cytoplasmic Incompatibility (CI) is causing embryonic lethality, the most common of them. Despite thatWolbachia-borne sterility has been proposed as an environmental friendly pest control method (Incompatible Insect Technique, IIT) since 1970s, the fact thatWolbachiamodifies important fitness components of its hosts sets severe barriers to IIT implementation. Mass rearing of Mediterranean fruit fly,Ceratitis capitata(medfly), is highly optimized given that this pest is a model species regarding the implementation of another sterility based pest control method, the Sterile Insect Technique (SIT). We used the medfly-Wolbachiasymbiotic association, as a model system, to study the effect of two differentWolbachiastrains, on the life history traits of 2C. capitatalines with different genomic background.

Results

Wolbachiaeffects are regulated by bothC. capitatagenetic background and theWolbachiastrain.Wolbachiainfection reduces fertility rates in bothC. capitatagenetic backgrounds and shortens the pre-pupa developmental duration in the GSS strain. On the other hand, regardless of the strain ofWolbachia(wCer2,wCer4) infection does not affect either the sex ratio or the longevity of adults.wCer4 infection imposed a reduction in females’ fecundity butwCer2 did not. Male mating competitiveness, adults flight ability and longevity under water and food deprivation were affected by both the genetic background of medfly and the strain ofWolbachia(genotype by genotype interaction).

Conclusion

Wolbachiainfection could alter important life history traits of mass-rearedC. capitatalines and therefore the response of each genotype on theWolbachiainfection should be considered toward ensuring the productivity of theWolbachia-infected insects under mass-rearing conditions.
The effects of occupational pollutants on the reproductive health of female informal street traders in Warwick junction, Durban, South Africa – a cross-sectional study
Authors: Hariparsad Sujatha , Naidoo Rajen N.
Published: December 2019

Background

Informal street traders are exposed on a daily basis to traffic emissions and biomass fuel smoke containing a variety of pollutants. These exposures are likely to place the female traders at increased risk for adverse reproductive outcomes.

Aim

The aim of this study was to compare the reproductive outcomes among street traders exposed to pollutants from their work-related activities and traders without such exposure.

Methods

A cross-sectional study was conducted among 305 female traders selected from exposed and non-exposed areas within the Warwick Junction trading hub, located in Durban, South Africa. Validated reproductive questionnaires and clinical assessments were conducted on all participants. Adverse reproductive outcomes such as low birth weight, spontaneous abortions and infertility were assessed.

Results

The mean age of the traders was 43.6 years (SD:12.1), mostly single (63%) and worked in trading hub for an average of 14 years. There were 876 pregnancies reported in the total sample. Traders pregnant while working in this location accounted for 120 pregnancies There was an increased risk of exposed traders having a low birth weight infant as compared to non-exposed traders (OR = 3.7; CI: 1.8, 7.6). Exposed traders were also almost 3 times more likely to be infertile as compared to non-exposed traders (OR = 2.6; CI: 1.6, 4.3).

Conclusions

This study has demonstrated that female street traders working within a trading hub in KwaZulu-Natal, South Africa; exposed to occupational pollutants show an association with developing infertility and low birth weight infants. Recommendations to mitigate adverse exposures have been suggested which include short term safety interventions and better cooking practices and future long term policy interventions.
Access to specialty healthcare in urban versus rural US populations: a systematic literature review
Authors: Cyr Melissa E. , Etchin Anna G. , Guthrie Barbara J. , Benneyan James C.
Published: December 2019

Background

Access to healthcare is a poorly defined construct, with insufficient understanding of differences in facilitators and barriers between US urban versus rural specialty care. We summarize recent literature and expand upon a prior conceptual access framework, adapted here specifically to urban and rural specialty care.

Methods

A systematic review was conducted of literature within the CINAHL, Medline, PubMed, PsycInfo, and ProQuest Social Sciences databases published between January 2013 and August 2018. Search terms targeted peer-reviewed academic publications pertinent to access to US urban or rural specialty healthcare. Exclusion criteria produced 67 articles. Findings were organized into an existing ten-dimension care access conceptual framework where possible, with additional topics grouped thematically into supplemental dimensions.

Results

Despite geographic and demographic differences, many access facilitators and barriers were common to both populations; only three dimensions did not contain literature addressing both urban and rural populations. The most commonly represented dimensions were availability and accommodation, appropriateness, and ability to perceive. Four new identified dimensions were: government and insurance policy, health organization and operations influence, stigma, and primary care and specialist influence.

Conclusions

While findings generally align with a preexisting framework, they also suggest several additional themes important to urban versus rural specialty care access.
Relationship between pharmaceutical pricing strategies with price, availability, and affordability of cardiovascular disease medicines: surveys in Qatar and Lebanon
Authors: Abdel Rida N. , Mohamed Ibrahim M. I. , Babar Z. U. D.
Published: December 2019

Background

Cardiovascular diseases are the leading cause of death in Lebanon and Qatar. When lifestyle modifications prove insufficient, medication becomes a cornerstone in controlling such diseases and saving lives. Price, availability, and affordability hinder the equitable access to medicines. The study aimed to assess prices, availability, and affordability of essential cardiovascular disease medicines in relation to pricing strategies in Qatar and Lebanon.

Methods

A cross-sectional survey using a variant of the World Health Organization and Health Action International (WHO/HAI) methodology as outlined in “Measuring medicine prices, availability, affordability and price components” (2008), second edition, was adopted. Prices and availability of 27 cardiovascular medicines were collected from public and private dispensing outlets. For international comparison, prices were adjusted to purchasing power parity. Data was analyzed across multiple sectors, within and across countries.

Results

A total of 15 public and private outlets were surveyed in each country. Prices were more uniform in Qatar than in Lebanon. In the public sector, medicines were free-of-charge in Lebanon and priced lower than the international reference prices in Qatar. The ratio of medicine unit price to international reference price in the private sectors surveyed are significantly higher than the acceptable threshold of 4. This ratio of originator brands and lowest priced generics in Qatar were up to two and five times those in Lebanon, respectively, even after adjusting for purchasing power parity. However, prices of lowest priced generics in the private sector were at least 35% cheaper in Qatar and 65% cheaper in Lebanon than their comparative originator brands. Medicines were more available in the private sector in Lebanon than in Qatar, but only the originator brand availability in the public sector in Qatar exceeded the WHO target of more than 80%. While affordable in the public sector in Qatar, four out of thirteen medicines exceeded the threshold in all private sectors covered. Hence, only the public sector in Qatar had a satisfying level of availability and affordability.

Conclusions

Except for the Qatari public sector, medicine prices, availability, and affordability are falling short from targets. Key policy decisions should be implemented to improve access to medicines.
Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel ring-stage survival assay
Authors: Walz Annabelle , Leroy Didier , Andenmatten Nicole , Mäser Pascal , Wittlin Sergio
Published: December 2019

Background

Drug efficacy against kelch 13 mutant malaria parasites can be determined in vitro with the ring-stage survival assay (RSA). The conventional assay protocol reflects the exposure profile of dihydroartemisinin.

Methods

Taking into account that other anti-malarial peroxides, such as the synthetic ozonides OZ439 (artefenomel) and OZ609, have different pharmacokinetics, the RSA was adjusted to the concentration–time profile of these ozonides in humans and a novel, semi-automated readout was introduced.

Results

When tested at clinically relevant parameters, it was shown that OZ439 and OZ609 are active against the Plasmodium falciparum clinical isolate Cam3.IR539T.

Conclusion

If the in vitro RSA does indeed predict the potency of compounds against parasites with increased tolerance to artemisinin and its derivatives, then the herein presented data suggest that following drug-pulses of at least 48 h, OZ439 and OZ609 will be highly potent against kelch 13 mutant isolates, such as P. falciparum Cam3.IR539T.
Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties
Authors: Camara Aissata , Haddad Mohamed , Reybier Karine , Traoré Mohamed Sahar , Baldé Mamadou Aliou , Royo Jade , Baldé Alpha Omar , Batigne Philippe , Haidara Mahamane , Baldé Elhadj Saidou , Coste Agnès , Baldé Aliou Mamadou , Aubouy Agnès
Published: December 2019

Background

The development of Plasmodium resistance to the last effective anti-malarial drugs necessitates the urgent development of new anti-malarial therapeutic strategies. To this end, plants are an important source of new molecules. The objective of this study was to evaluate the anti-malarial effects of Terminalia albida, a plant used in Guinean traditional medicine, as well as its anti-inflammatory and antioxidant properties, which may be useful in treating cases of severe malaria.

Methods

In vitro antiplasmodial activity was evaluated on a chloroquine-resistant strain of Plasmodium falciparum (K-1). In vivo efficacy of the plant extract was measured in the experimental cerebral malaria model based on Plasmodium berghei (strain ANKA) infection. Mice brains were harvested on Day 7–8 post-infection, and T cells recruitment to the brain, expression levels of pro- and anti-inflammatory markers were measured by flow cytometry, RT-qPCR and ELISA. Non-malarial in vitro models of inflammation and oxidative response were used to confirm Terminalia albida effects. Constituents of Terminalia albida extract were characterized by ultra‐high performance liquid chromatography coupled with high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation patterns.

Results

In vitro antiplasmodial activity of Terminalia albida was confirmed with an IC50 of 1.5 μg/mL. In vivo, Terminalia albida treatment greatly increased survival rates in P. berghei-infected mice. Treated mice were all alive until Day 12, and the survival rate was 50% on Day 20. Terminalia albida treatment also significantly decreased parasitaemia by 100% on Day 4 and 89% on Day 7 post-infection. In vivo anti-malarial activity was related to anti-inflammatory properties, as Terminalia albida treatment decreased T lymphocyte recruitment and expression of pro-inflammatory markers in brains of treated mice. These properties were confirmed in vitro in the non-malarial model. In vitro, Terminalia albida also demonstrated a remarkable dose-dependent neutralization activity of reactive oxygen species. Twelve compounds were putatively identified in Terminalia albida stem bark. Among them, several molecules already identified may be responsible for the different biological activities observed, especially tannins and triterpenoids.

Conclusion

The traditional use of Terminalia albida in the treatment of malaria was validated through the combination of in vitro and in vivo studies.
Widespread and widely widening? Examining absolute socioeconomic health inequalities in northern Sweden across twelve health indicators
Authors: Degerlund Maldi Kinza , San Sebastian Miguel , Gustafsson Per E. , Jonsson Frida
Published: December 2019

Background

Socioeconomic inequalities in health is a widely studied topic. However, epidemiological research tends to focus on one or a few outcomes conditioned on one indicator, overlooking the fact that health inequalities can vary depending on the outcome studied and the indicator used. To bridge this gap, this study aims to provide a comprehensive picture of the patterns of socioeconomic health inequalities in Northern Sweden over time, across a range of health outcomes, using an ‘outcome-wide’ epidemiological approach.

Method

Cross-sectional data from three waves of the ‘Health on Equal Terms’ survey, distributed in 2006, 2010 and 2014 were used. Firstly, socioeconomic inequalities by income and education for twelve outcomes (self-rated health, self-rated dental health, overweight, hypertension, diabetes, long-term illness, stress, depression, psychological distress, smoking, risky alcohol consumption, and physical inactivity) were examined by calculating the Slope Index of Inequality. Secondly, time trends for each outcome and socioeconomic indicator were estimated.

Results

Income inequalities increased for psychological distress and physical inactivity in men as well as for self-rated health, overweight, hypertension, long-term illness, and smoking among women. Educational inequalities increased for hypertension, long-term illness, and stress (the latter favouring lower education) in women. The only instance of decreasing income inequalities was seen for long-term illness in men, while education inequalities decreased for long-term illness in men and poor self-rated health, poor self-rated dental health, and smoking in women.

Conclusion

Patterns of absolute socioeconomic inequalities in health vary by health and socioeconomic indicator, as well as between men and women. Overall, trends appear more stagnant in men while they fluctuate in women. Income inequalities seem to be generally greater than educational inequalities when looking across several different health indicators, a message that can only be derived from this type of outcome-wide study. These disparate findings suggest that generalised and universal statements about the development of health inequalities can be too simplistic and potentially misleading. Nonetheless, despite inequalities being complex, they do exist and tend to increase. Thus, an outcome-wide approach is a valuable method which should be utilised to generate evidence for prioritisations of policy decisions.
Socio-economic inequality and inequity in use of health care services in Kenya: evidence from the fourth Kenya household health expenditure and utilization survey
Authors: Ilinca Stefania , Di Giorgio Laura , Salari Paola , Chuma Jane
Published: December 2019

Background

Kenya is experiencing persistently high levels of inequity in health and access to care services. In 2018, decades of sustained policy efforts to promote equitable, affordable and quality health services have culminated in the launch of a universal health coverage scheme, initially piloted in four Kenyan counties and planned for national rollout by 2022. Our study aims to contribute to monitoring and evaluation efforts alongside policy implementation, by establishing a detailed, baseline assessment of socio-economic inequality and inequity in health care utilization in Kenya shortly before the policy launch.

Methods

We use concentration curves and corrected concentration indexes to measure socio-economic inequality in care use and the horizontal inequity index as a measure of inequity in care utilization for three types of care services: outpatient care, inpatient care and preventive and promotive care. Further insights into the individual and household level characteristics that determine observed inequality are derived through decomposition analysis.

Results

We find significant inequality and inequity in the use of all types of care services favouring richer population groups, with particularly pronounced levels for preventive and inpatient care services. These are driven primarily by differences in living standards and educational achievement, while the region of residence is a key driver for inequality in preventive care use only. Pro-rich inequalities are particularly pronounced for care provided in privately owned facilities, while public providers serve a much larger share of individuals from lower socio-economic groups.

Conclusions

Through its focus on increasing affordability of care for all Kenyans, the newly launched universal health coverage scheme represents a crucial step towards reducing disparities in health care utilization. However in order to achieve equity in health and access to care such efforts must be paralleled by multi-sectoral approaches to address all key drivers of inequity: persistent poverty, disparities in living standards and educational achievement, as well as regional differences in availability and accessibility of care.
p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
Authors: Moles Ramona , Sarkis Sarkis , Galli Veronica , Omsland Maria , Purcell Damian F. J. , Yurick David , Khoury Georges , Pise-Masison Cynthia A. , Franchini Genoveffa
Published: December 2019

The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus’s most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly splicedTax-orf IImRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.
Linezolid versus daptomycin treatment for periprosthetic joint infections: a retrospective cohort study
Authors: Sawada Masahiro , Oe Kenichi , Hirata Masayuki , Kawamura Hiroshi , Ueda Narumi , Nakamura Tomohisa , Iida Hirokazu , Saito Takanori
Published: December 2019

Background

Linezolid (LZD) and daptomycin (DAP) are predominantly used to target gram-positive pathogens; however, treatment effectiveness and adverse reactions for periprosthetic joint infections (PJIs) remain unknown. The aim of this study was to compare the effectiveness and adverse reactions of LZD and DAP for PJIs.

Methods

This study retrospectively evaluated 82 patients between June 2009 and December 2017, to compare the effectiveness of LZD (group L, n = 39) and DAP (group D, n = 43) for treatment of PJIs harboring gram-positive microorganisms. Surgical options used with LZD or DAP therapy included implant retention, implant removal, and a shift to another appropriate antibiotic. Infection control was defined as not requiring implant removal after the final treatment.

Results

Gram-positive pathogens were isolated from 72% of group L and 70% of group D patients, respectively. Whole infection control rates against gram-positive pathogens in groups L and D were 79% and 77%, respectively. Furthermore, infection control rates were 94% and 58% in group L and 75% and 80% in group D, without and with implant removal, respectively. Significantly higher clinical success rates and lower adverse event rates were observed in group D, including higher red blood cell and platelet counts and lower C-reactive protein (CRP) levels.

Conclusions

Although the effectiveness of LZD and DAP was equivalent in terms of infection control rates for refractory PJIs with gram-positive pathogens, DAP therapy significantly decreased CRP levels and caused fewer adverse events than LZD treatment.
Therapeutic effect of percutaneous kyphoplasty combined with anti-osteoporosis drug on postmenopausal women with osteoporotic vertebral compression fracture and analysis of postoperative bone cement leakage risk factors: a retrospective cohort study
Authors: Huang Shuaihao , Zhu Xiaowen , Xiao Dan , Zhuang Jianxiong , Liang Guoyan , Liang Changxiang , Zheng Xiaoqing , Ke Yuhong , Chang Yunbing
Published: December 2019

Background

The purpose of this study is to explore the therapeutic effect of percutaneous kyphoplasty (PKP) combined with anti-osteoporosis drug, zoledronic acid, on postmenopausal women with osteoporotic vertebral compression fracture (OVCF) and to perform an analysis of postoperative bone cement leakage risk factors.

Methods

A total of 112 OVCF patients, according to therapeutic regimens, were divided into control group (n = 52, treated with PKP) and observation group (n = 60, treated with PKP and zoledronic acid injection).

Results

Postoperative tumor necrosis factor-α and interleukin-6 levels were significantly decreased in the two groups, compared with those before treatment (both P < 0.05); bone mineral density (BMD), serum bone gla protein (BGP), and vertebral height ratio of injured vertebrae were significantly increased, and procollagen type I N-terminal propeptide (PINP), Cobb angle, visual analogue scale/score (VAS), and Oswestry disability index (ODI) were significantly decreased compared with those before treatment (all P < 0.05). There were significantly higher changes in difference value of BMD, PINP, BGP, vertebral height ratio of injured vertebrae, Cobb angle, VAS, and ODI levels and significantly better therapeutic effect in the observation group than those in the control group (all P < 0.05). Multivariate logistic regression analysis showed that the use of zoledronic acid, vertebral height ratio of injured vertebrae, and ODI were independent factors affecting the therapeutic effect, and that the dosage of bone cement, and peripheral vertebrae wall damage were independent risk factors causing postoperative bone cement leakage. There were no significant differences in postoperative bone cement leakage rate between the two groups.

Conclusions

Peripheral vertebrae wall damage and the dosage of bone cement are independent risk factors causing bone cement leakage in OVCF patients treated with PKP. PKP combined with zoledronic acid has an improvement effect on the condition of postmenopausal women with OVCF and reduces the inflammation and pain in patients, which is beneficial to clinical treatment.
Elacestrant (RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors
Authors: Patel Hitisha K. , Tao Nianjun , Lee Kyung-Min , Huerta Mariela , Arlt Heike , Mullarkey Tara , Troy Steven , Arteaga Carlos L. , Bihani Teeru
Published: December 2019

Background

Addition of CDK4/6 inhibitors (CDK4/6i) to endocrine therapy significantly increased progression-free survival, leading to their approval and incorporation into the metastatic breast cancer treatment paradigm. With these inhibitors being routinely used for patients with advanced estrogen receptor-positive (ER+) breast cancer, resistance to these agents and its impact on subsequent therapy needs to be understood. Considering the central role of ER in driving the growth of ER+ breast cancers, and thus endocrine agents being a mainstay in the treatment paradigm, the effects of prior CDK4/6i exposure on ER signaling and the relevance of ER-targeted therapy are important to investigate. The objective of this study was to evaluate the anti-tumor activity of elacestrant, a novel oral selective estrogen receptor degrader (SERD), in preclinical models of CDK4/6i resistance.

Methods

Elacestrant was evaluated as a single agent, and in combination with alpelisib or everolimus, in multiple in vitro models and patient-derived xenografts that represent acquired and “de novo” CDK4/6i resistance.

Results

Elacestrant demonstrated growth inhibition in cells resistant to all three approved CDK4/6i (palbociclib, abemaciclib, ribociclib) in both ESR1 wild-type and mutant backgrounds. Furthermore, we demonstrated that elacestrant, as a single agent and in combination, inhibited growth of patient-derived xenografts that have been derived from a patient previously treated with a CDK4/6i or exhibit de novo resistance to CDK4/6i. While the resistant lines demonstrate distinct alterations in cell cycle modulators, this did not affect elacestrant’s anti-tumor activity. In fact, we observe that elacestrant downregulates several key cell cycle players and halts cell cycle progression in vitro and in vivo.

Conclusions

We demonstrate that breast cancer tumor cells continue to rely on ER signaling to drive tumor growth despite exposure to CDK4/6i inhibitors. Importantly, elacestrant can inhibit this ER-dependent growth despite previously reported mechanisms of CDK4/6i resistance observed such as Rb loss, CDK6 overexpression, upregulated cyclinE1 and E2F1, among others. These data provide a scientific rationale for the evaluation of elacestrant in a post-CDK4/6i patient population. Additionally, elacestrant may also serve as an endocrine backbone for rational combinations to combat resistance.
Expression of a rK39 homologue from an Iranian Leishmania infantum isolate in Leishmania tarentolae for serodiagnosis of visceral leishmaniasis
Authors: Rezaei Zahra , Van Reet Nick , Pouladfar Gholamreza , Kühne Vera , Ramezani Amin , Sarkari Bahador , Pourabbas Bahman , Büscher Philippe
Published: December 2019

Background

Kinesin-related gene diversity among strains and species of Leishmania may impact the sensitivity and specificity of serodiagnostic tests for visceral leishmaniasis (VL).

Methods

In this study, we report on the recombinant expression of this novel Iranian Leishmania infantum (MCAN14/47) homologue of rK39 (Li-rK39), in L. tarentolae. The diagnostic potential of the Li-rK39 antigen was evaluated in an ELISA, using sera from 100 VL patients, 190 healthy endemic controls, 46 non-endemic healthy controls and 47 patients with other infections.

Results

The results showed a sensitivity of 96% and a specificity of 93.8%. A commercial rK39 immunochromatographic test (ICT) was 90% sensitive and 100% specific on the same cohort.

Conclusions

Here, we show that the K39 gene from an Iranian L. infantum isolate is heterozygous as compared to the sequence of the Brazilian L. infantum (former L. chagasi), whose antigen is incorporated in most rK39-based immunochromatographic tests. Therefore, Li-rK39 has the potential to be used as an alternative for VL diagnosis in Iran.
Biological motion perception in autism spectrum disorder: a meta-analysis
Authors: Todorova Greta Krasimirova , Hatton Rosalind Elizabeth Mcbean , Pollick Frank Earl
Published: December 2019

Background

Biological motion, namely the movement of others, conveys information that allows the identification of affective states and intentions. This makes it an important avenue of research in autism spectrum disorder where social functioning is one of the main areas of difficulty. We aimed to create a quantitative summary of previous findings and investigate potential factors, which could explain the variable results found in the literature investigating biological motion perception in autism.

Methods

A search from five electronic databases yielded 52 papers eligible for a quantitative summarisation, including behavioural, eye-tracking, electroencephalography and functional magnetic resonance imaging studies.

Results

Using a three-level random effects meta-analytic approach, we found that individuals with autism generally showed decreased performance in perception and interpretation of biological motion. Results additionally suggest decreased performance when higher order information, such as emotion, is required. Moreover, with the increase of age, the difference between autistic and neurotypical individuals decreases, with children showing the largest effect size overall.

Conclusion

We highlight the need for methodological standards and clear distinctions between the age groups and paradigms utilised when trying to interpret differences between the two populations.
Advanced imaging in adult diffusely infiltrating low-grade gliomas
Authors: Bulakbaşı Nail , Paksoy Yahya
Published: December 2019

The adult diffusely infiltrating low-grade gliomas (LGGs) are typically IDH mutant and slow-growing gliomas having moderately increased cellularity generally without mitosis, necrosis, and microvascular proliferation. Supra-total resection of LGG significantly increases the overall survival by delaying malignant transformation compared with a simple debulking so accurate MR diagnosis is crucial for treatment planning. Data from meta-analysis support the addition of diffusion and perfusion-weighted MR imaging and MR spectroscopy in the diagnosis of suspected LGG. Typically, LGG has lower cellularity (ADCmin), angiogenesis (rCBVmax), capillary permeability (Ktrans), and mitotic activity (Cho/Cr ratio) compared to high-grade glioma. The identification of 2-hydroxyglutarate by MR spectroscopy can reflect the IDH status of the tumor. The initial low ADCmin, high rCBVmax, and Ktrans values are consistent with the poor prognosis. The gradual increase in intratumoral Cho/Cr ratio and rCBVmax values are well correlated with tumor progression. Besides MR-based technical artifacts, which are minimized by the voxel-based assessment of data obtained by histogram analysis, the problems derived from the diversity and the analysis of imaging data should be solved by using artificial intelligence techniques. The quantitative multiparametric MR imaging of LGG can either improve the diagnostic accuracy of their differential diagnosis or assess their prognosis.
MicroRNA-145 engineered bone marrow-derived mesenchymal stem cells alleviated erectile dysfunction in aged rats
Authors: Liu Qiwei , Cui Yubin , Lin Haojian , Hu Daoyuan , Qi Tao , Wang Bo , Huang Zhansen , Chen Jun , Li Ke , Xiao Hengjun
Published: December 2019

Background

Aging is one of the dominant factors contributing to erectile dysfunction (ED), and effective treatments for age-associated ED are urgently demanded. In this study, the therapeutic efficiency of bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing microRNA-145 (miR-145) was evaluated in ED.

Methods

Sixty male Sprague-Dawley rats (24 months old) were randomly divided into 4 treatment groups (n = 15/group): PBS (control), BMSCs, BMSCs transfected with a blank vector (vector-BMSCs), and BMSCs transfected with a lentivirus overexpressing miR-145 (OE-miR-145-BMSCs). Fourteen days after transplantation of BMSCs, erectile function was evaluated by measuring intra-cavernous pressure (ICP) and mean arterial pressure (MAP). Subsequently, penile erectile tissues were harvested and subjected to Masson staining, qRT-PCR, immunofluorescence staining, dual luciferase assay, and Western blot analysis.

Results

Fourteen days after transplantation, the ICP/MAP was 0.79 ± 0.05 in the OE-miR-145-BMSC group, 0.61 ± 0.06 in the BMSC group, 0.57 ± 0.06 in the vector-BMSC group, and 0.3 ± 0.01 in the PBS group. Treatment with OE-miR-145-BMSCs significantly improved ED (P < 0.05), and the treatment increased the smooth muscle content in the penis tissues of ED rats (P < 0.05). In the OE-miR-145-BMSC group, the expression levels of α-SMA, desmin, and SM-MHC were higher than they were in the other ED groups (P < 0.05). In addition, the levels of collagen 1, MMP2, and p-Smad2 in the BMSC-treated group, especially in the OE-miR-145-BMSC group, were lower than those in the control group (P < 0.05).

Conclusions

MicroRNA-145 engineered BMSCs effectively attenuate age-related ED. Transplantation of miR-145-overexpressing BMSCs may provide a promising novel avenue for age-associated ED therapy.
Solutions to Riemann–Liouville fractional integrodifferential equations via fractional resolvents
Authors: Ji Shaochun , Yang Dandan
Published: December 2019

This paper is concerned with the semilinear fractional integrodifferential system with Riemann–Liouville fractional derivative. Firstly, we introduce the suitable$C_{1-\alpha }$C1−α-solution to Riemann–Liouville fractional integrodifferential equations in the new frame of fractional resolvents. Some properties of fractional resolvents are given. Then we discuss the sufficient conditions for the existence of solutions without the Lipschitz assumptions to nonlinear item. Finally, an example on fractional partial differential equations is presented to illustrate our abstract results.
Antimicrobial Resistance in the Asia Pacific region: a meeting report
Authors: Yam Esabelle Lo Yan , Hsu Li Yang , Yap Eric Peng-Huat , Yeo Tsin Wen , Lee Vernon , Schlundt Joergen , Lwin May O. , Limmathurotsakul Direk , Jit Mark , Dedon Peter , Turner Paul , Wilder-Smith Annelies
Published: December 2019

The Asia Pacific region, home to two-thirds of the world’s population and ten of the least developed countries, is considered a regional hot-spot for the emergence and spread of antimicrobial resistance (AMR). Despite this, there is a dearth of high-quality regional data on the extent of AMR. Recognising the urgency to close this gap, Singapore organised a meeting to discuss the problems in the region and frame a call for action. Representatives from across the region and beyond attended the meeting on the “Antimicrobial Resistance in the Asia Pacific & its impact on Singapore” held in November 2018. This meeting report is a summary of the discussions on the challenges and progress in surveillance, drivers and levers of AMR emergence, and the promising innovations and technologies that could be used to combat the increasing threat of AMR in the region. Enhanced surveillance and research to provide improved evidence-based strategies and policies are needed. The major themes that emerged for an action plan are working towards a tailored solution for the region by harnessing the One Health approach, enhancing inter-country collaborations, and collaboratively leverage upon new emerging technologies. A regionally coordinated effort that is target-driven, sustainable and builds on a framework facilitating communication and governance will strengthen the fight against AMR in the Asia Pacific region.
Successful conservative treatment of spontaneous intrathoracic esophageal perforation using a temporary covered esophageal stent with a check valve: a case report
Authors: Matsumoto Ryu , Sasaki Ken , Omoto Itaru , Noda Masahiro , Uchikado Yasuto , Arigami Takaaki , Kita Yoshiaki , Mori Shinichiro , Maemura Kosei , Natsugoe Shoji
Published: December 2019

Background

Spontaneous esophageal perforation is a potentially life-threatening condition with high morbidity and mortality rates. While surgical treatment has been employed for esophageal perforation, we have adopted conservative treatment with an esophageal stent for patients in a poor physical condition because we consider controlling sepsis and improving the physical status are the highest priorities; additionally, the surgical trauma could be fatal for these patients.

Case presentation

A 60-year-old male complaining of left chest and back pain after vomiting was transferred to a local hospital. Computed tomography and chest X-ray examinations showed left tension pneumothorax, pneumomediastinum, and bilateral pleural effusion suspicious of spontaneous intrathoracic esophageal perforation. He was transferred to our hospital for further treatment. After arrival, he developed septic shock with acute respiratory failure. We considered that surgical treatment was too invasive and chose conservative treatment with an esophageal stent. Under general anesthesia, we first inserted a 20-Fr. trocar in the left posterior pleural space, and a large volume of the dark pleural effusion was discharged. We then performed endoscopy and found a pinhole perforation in the left posterolateral wall of the lower esophagus. We inserted both a silicon-covered esophageal stent with a check valve and a double elemental diet (W-ED) tube. We then inserted an 18-Fr. trocar into the left anterior wall. These procedures were performed less than 24 h after onset. As intensive medical care, the patient was administered broad-spectrum antibiotics and catecholamine. The two trocars and the W-ED tube were under continuous suction at − 5 cmH2O and at − 20 cmH2O every 30 s. On the 6th day, we inserted an additional thoracic drainage tube into the left pleura under CT guidance. The patient was discharged from the ICU to the general ward on the 7th day. We removed the stent almost triweekly, and the esophageal perforation was completely healed on the 45th day. He was discharged home on the 70th day.

Conclusion

Conservative treatment with a temporary self-expanding covered stent with a check valve, sufficient drainage, and W-ED tube nutrition was useful and effective in this unstable case of spontaneous intrathoracic esophageal perforation.
Feasibility, user experiences, and preliminary effect of Conversation Cards for Adolescents© on collaborative goal-setting and behavior change: protocol for a pilot randomized controlled trial
Authors: Kebbe M. , Farmer A. , Dyson M. P. , Scott S. D. , McHugh T. L. F. , Lappa S. , Rajani H. , Ladha T. , Islam B. , Jacoby L. , Nasir F. , Talwar K. , Wincott J. L. , Zhang M. , Ball G. D. C.
Published: December 2019

Background

Adolescents and providers can benefit from practical tools targeting lifestyle modification for obesity prevention and management. We createdConversation Cards for Adolescents©(CCAs), a patient-centered communication and behavior change tool for adolescents and providers to use in clinical practice. The purpose of our study is to (i) assess the feasibility of CCAs in a real-world, practice setting to inform full-scale trial procedures, (ii) assess user experiences of CCAs, and (iii) determine the preliminary effect of CCAs on changing behavioral and affective-cognitive outcomes among adolescents.

Methods

Starting in early 2019, this prospective study is a nested mixed-methods, theory-driven, and pragmatic pilot randomized controlled trial with a goal to enroll 50 adolescents (13–17 years old) and 9 physicians practicing at the Northeast Community Health Centre in Edmonton, Alberta, Canada. Adolescents will collaboratively set one S.M.A.R.T. (specific, measurable, attainable, realistic, timely) goal with their physician to implement over a 3-week period; however, only those randomized to the experimental group will use CCAs to inform their goal. Outcome assessments at baseline and follow-up (3 weeks post-baseline) will include behavioral, affective-cognitive, and process-related outcomes.

Discussion

In examining the feasibility, user experiences, and preliminary effect of CCAs, our study will add contributions to the obesity literature on lifestyle modifications among adolescents in a real-world, practice setting as well as inform the scalability of our approach for a full-scale effectiveness randomized controlled trial on behavior change.

Trial registration

ClinicalTrials.gov Identifier:NCT03821896.