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AnteayerPLOS ONE Medicine&Health

On-line parameter identification of the lumped arterial system model: A simulation study

by Feng Huang, Shunv Ying

A lumped model of the arterial system has been used in constructing a hybrid mock loop due to its real-time response. However, the parameters of the model are always from a general case and not adapted to a specific patient. In this study, we focused on on-line parameter identification of the lumped model of the arterial system that could be used for a specific patient. A five-element lumped arterial model is adopted in this study, in which the five parameters are to be determined. The aortic flow rate and the venous pressure are chosen as the inputs of the model, and aortic pressure as the output. An iterative optimization based on the established state space equations of the five-element model is used to seek the best parameter values by minimizing the difference between the model prediction and the previously obtained aortic pressure. The method is validated using simulated data from a complete numerical cardiovascular model. Results show that the method can track the dynamic variation of the parameters very well. Finally, a sensitivity analysis of the model parameters is conducted to interpret the effect of parameter changes. The good performance of the identification demonstrates the potential application of this method to customize a hybrid mock loop for a specific patient or clinically monitor the arterial vessel characteristics in real time.

Characterising the influence of cerebellum on the neuroplastic modulation of intracortical motor circuits

by George M. Opie, John G. Semmler

The cerebellum (CB) has extensive connections with both cortical and subcortical areas of the brain, and is known to strongly influence function in areas it projects to. In particular, research using non-invasive brain stimulation (NIBS) has shown that CB projections to primary motor cortex (M1) are likely important for facilitating the learning of new motor skills, and that this process may involve modulation of late indirect (I) wave inputs in M1. However, the nature of this relationship remains unclear, particularly in regards to how CB influences the contribution of the I-wave circuits to neuroplastic changes in M1. Within the proposed research, we will therefore investigate how CB effects neuroplasticity of the I-wave generating circuits. This will be achieved by downregulating CB excitability while concurrently applying a neuroplastic intervention that specifically targets the I-wave circuitry. The outcomes of this study will provide valuable neurophysiological insight into key aspects of the motor network, and may inform the development of optimized interventions for modifying motor learning in a targeted way.

Association between tooth loss and handgrip strength in a general adult population

by Ziqi Zhou, Yeqing Gu, Qing Zhang, Li Liu, Hongmei Wu, Ge Meng, Xue Bao, Shunming Zhang, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Yue Zhao, Kaijun Niu

Tooth loss is a prevailing condition in China due to the high prevalence of oral diseases. Since previous studies explored the association between tooth loss and handgrip strength showed incongruous results, the aim of this study was to investigate the association between tooth loss and handgrip strength in Tianjin, China. Cross-sectional data in the present study used baseline data of Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study during 2013–2016. Eligible adults (n = 26275) were classified into four groups depending on the number of missing teeth (excluding third molars): 0, 1–2, 3–5 and ≥6. Handgrip strength was measured using a handheld type dynamometer. Analysis of covariance was used to examine the relationships between tooth loss and handgrip strength and handgrip strength per body weight according to gender. After adjustment for potential confounders, the relationships existed between increasing categories of tooth loss and handgrip strength, as well as handgrip strength per weight. The data of stratified analysis showed that there was a trending association between decreased handgrip strength and fewer retained teeth both in males and females less than 60 years of age (P for trend P

Effect of optical correction by fully corrected glasses on postural stability

by Ji In Bae, Dong-Sik Yu, Sang-Yeob Kim

Although various previous studies have reported that the experimentally induced refractive errors interfered with postural control, few studies have demonstrated the optical correction effect of wearing glasses. The purpose of this study was to investigate whether wearing full corrected glasses to correct myopia and hyperopia can have a positive effect on postural stability. To this end, a total of 34 subjects (19 males and 15 females) of an average age of 22.38 ± 2.41-years-old participated in this study. After measuring the full corrected powers of refractive errors of subjects through subjective refraction, updated glasses were provided to 17 myopic subjects and first time glasses were provided to 17 hyperopic subjects as full corrected glasses, respectively. Postural evaluation was carried out using the TETRAX biofeedback system, after which we compared and analyzed the postural instability index and sway power index before and after wearing full corrected glasses. When updated and old glasses for correcting myopia were worn, the postural instability index was significantly reduced, and the sway power index was statistically decreased only in the mid-high frequency region associated with the somatic system, compared to the no glasses state, respectively. However, after wearing first time glasses for hyperopia correction, no significant difference was found in the postural instability index or sway power index. We suggest that providing optimal visual information through the optical correction of myopic refractive error is a useful approach that can lead to synergistic effects of somatic functions involved in postural control. Consequently, we demonstrated that wearing glasses to fully correct the refractive errors has a positive effect on increasing postural control in static posture. Our results may have important clinical implications in the field of optometry and balance evaluation.

Intra-session and inter-rater reliability of spatial frequency analysis methods in skeletal muscle

by Scott K. Crawford, Kenneth S. Lee, Greg R. Bashford, Bryan C. Heiderscheit

Spatial frequency analysis (SFA) is a quantitative ultrasound (US) method originally developed to assess intratendinous tissue structure. This method may also be advantageous in assessing other musculoskeletal tissues. Although SFA has been shown to be a reliable assessment strategy in tendon tissue, its reliability in muscle has not been investigated. The purpose of this study was to examine the reliability of spatial frequency parameter measurement for a large muscle group within a healthy population. Ten participants with no history of lower extremity surgery or hamstring strain injury volunteered. Longitudinal B-mode images were collected in three different locations across the hamstring muscles. Following a short rest, the entire imaging procedure was repeated. B-mode images were processed by manually drawing a region of interest (ROI) about the entire muscle thickness. Four spatial frequency parameters of interest were extracted from the image ROIs. Intra- and inter-rater reliabilities of extracted SFA parameters were performed. Test-retest reliability of the image acquisition procedure was assessed between repeat trials. Intraclass correlation coefficients showed high intra- and inter-rater reliability (ICC(3,1) > 0.9 for all parameters) and good to moderate test-retest reliability (ICC(3,1) > 0.50) between trials. No differences in parameter values were observed between trials across all muscles and locations (p > 0.05). The high reliability metrics suggest that SFA will be useful for future studies assessing muscle tissue structure, and may have value in assessing muscular adaptations following injury and during recovery.

Impact of old age on the association between in-center extended-hours hemodialysis and mortality in patients on incident hemodialysis

by Masaki Okazaki, Daijo Inaguma, Takahiro Imaizumi, Manabu Hishida, Shimon Kurasawa, Yoko Kubo, Sawako Kato, Yoshinari Yasuda, Takayuki Katsuno, Fumika Kaneda, Shoichi Maruyama

With the global problem of aging, it has become more difficult to improve the prognosis of older dialysis patients. Extended-hours hemodialysis offers longer treatment time compared to conventional hemodialysis regimen and provides favorable metabolic status, hemodynamic stability, and increased dietary intake. Despite prior studies reporting that in-center extended-hours hemodialysis can reduce the mortality rate, the treatment impact on elderly patients remains unclear. Therefore, we examined the association between extended-hours hemodialysis compared to conventional hemodialysis and all-cause mortality. Survival analyses using Cox proportional hazard model with multivariable adjustments and propensity-score based method were performed to compare mortality risk between 198 consecutive patients who started in-center extended-hours hemodialysis (Extended-HD) and 1407 consecutive patients who initiated conventional hemodialysis. The median age was 67.1 years in the Extended-HD group and 70.7 years in the conventional hemodialysis group. Extended-HD was associated with lower all-cause mortality in overall patients and the subgroup >70 years (adjusted hazard ratios of 0.60 [95% CI, 0.39–0.91] and 0.35 [95% CI, 0.18–0.69], respectively). There was a significant interaction between age >70 years and Extended-HD. In conclusion, extended-hours hemodialysis was associated with a lower mortality rate, especially in elderly patients.

Isolation and diversity of sediment bacteria in the hypersaline aiding lake, China

by Tong-Wei Guan, Yi-Jin Lin, Meng-Ying Ou, Ke-Bao Chen

Halophiles are relatively unexplored as potential sources of novel species. However, little is known about the culturable bacterial diversity thrive in hypersaline lakes. In this work, a total of 343 bacteria from sediment samples of Aiding Lake, China, were isolated using nine different media supplemented with 5% or 15% (w/v) NaCl. The number of species and genera of bacteria recovered from the different media varied, indicating the need to optimize the isolation conditions. The results showed an unexpected level of bacterial diversity, with four phyla (Actinobacteria, Firmicutes, Proteobacteria, and Rhodothermaeota), fourteen orders (Actinopolysporales, Alteromonadales, Bacillales, Balneolales, Chromatiales, Glycomycetales, Jiangellales, Micrococcales, Micromonosporales, Oceanospirillales, Pseudonocardiales, Rhizobiales, Streptomycetales, and Streptosporangiales), including 17 families, 43 genera (including two novel genera), and 71 species (including four novel species). The predominant phyla included Actinobacteria and Firmicutes and the predominant genera included Actinopolyspora, Gracilibacillus, Halomonas, Nocardiopsis, and Streptomyces. To our knowledge, this is the first time that members of phylum Rhodothermaeota were identified in sediment samples from a salt lake.

A molecular and epidemiological study of <i>Vibrio cholerae</i> isolates from cholera outbreaks in southern Ghana

by Emelia Konadu Danso, Prince Asare, Isaac Darko Otchere, Lorenzo Moses Akyeh, Adwoa Asante-Poku, Samuel Yaw Aboagye, Stephen Osei-Wusu, David Opare, Francine Ntoumi, Alimuddin Zumla, Samuel Duodu, Dorothy Yeboah-Manu

Cholera remains a major global public health threat and continuous emergence of new Vibrio cholerae strains is of major concern. We conducted a molecular epidemiological study to detect virulence markers and antimicrobial resistance patterns of V. cholerae isolates obtained from the 2012–2015 cholera outbreaks in Ghana. Archived clinical isolates obtained from the 2012, 2014 and 2015 cholera outbreaks in Ghana were revived by culture and subjected to microscopy, biochemical identification, serotyping, antibiotic susceptibility testing, molecular detection of distinct virulence factors and Multi-Locus Variable-Number of Tandem-Repeat Analysis (MLVA). Of 277 isolates analysed, 168 (60.6%) were confirmed to be V. cholerae and 109 (39.4%) isolates constituted other bacteria (Escherichia coli, Aeromonas sobria, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococci faecalis). Serotyping the V. cholerae isolates identified 151 (89.9%) as Ogawa, 3 (1.8%) as Inaba and 14 (8.3%) as non-O1/O139 serogroup. The O1 serogroup isolates (154/168, 91.7%) carried the cholera toxin ctxB gene as detected by PCR. Additional virulence genes detected include zot, tcpA, ace, rtxC, toxR, rtxA, tcpP, hlyA and tagA. The most common and rare virulence factors detected among the isolates were rtxC (165 isolates) and tcpP (50 isolates) respectively. All isolates from 2014 and 2015 were multidrug resistant against the selected antibiotics. MLVA differentiated the isolates into 2 large unique clones A and B, with each predominating in a particular year. Spatial analysis showed clustering of most isolates at Ablekuma sub-district. Identification of several virulence genes among the two different genotypes of V. cholerae isolates and resistance to first- and second-line antibiotics, calls for scaleup of preventive strategies to reduce transmission, and strengthening of public health laboratories for rapid antimicrobial susceptibility testing to guide accurate treatment. Our findings support the current WHO licensed cholera vaccines which include both O1 Inaba and Ogawa serotypes.

Managing hypertension in frail oldest-old—The role of guideline use by general practitioners from 29 countries

by Céline Roulet, Zsofia Rozsnyai, Katharina Tabea Jungo, Milly A. van der Ploeg, Carmen Floriani, Donata Kurpas, Shlomo Vinker, Sanda Kreitmayer Pestic, Ferdinando Petrazzuoli, Kathryn Hoffmann, Rita P. A. Viegas, Christian Mallen, Athina Tatsioni, Hubert Maisonneuve, Claire Collins, Heidrun Lingner, Rosy Tsopra, Yolanda Mueller, Rosalinde K. E. Poortvliet, Jacobijn Gussekloo, Sven Streit


The best management of hypertension in frail oldest-old (≥80 years of age) remains unclear and we still lack guidelines that provide specific recommendations. Our study aims to investigate guideline use in general practitioners (GPs) and to examine if guideline use relates to different decisions when managing hypertension in frail oldest-old.


Cross-sectional study among currently active GPs from 29 countries using a case-vignettes survey.


GPs participated in a survey with case-vignettes of frail oldest-olds varying in systolic blood pressure (SBP) levels and cardiovascular disease (CVD). GPs from 26 European countries and from Brazil, Israel and New Zealand were invited. We compared the percentage of GPs reporting using guidelines per country and further stratified on the most frequently mentioned guidelines. To adjust for patient characteristics (SBP, CVD and GPs’ sex, years of experience, prevalence of oldest-old and location of their practice), we used a mixed-effects regression model accounting for clustering within countries.


Overall, 2,543 GPs from 29 countries were included. 59.4% of them reported to use guidelines. Higher guideline use was found in female (p = 0.031) and less-experienced GPs (p Conclusion

Many GPs reported using guidelines to manage hypertension in frail oldest-old patients, however guideline users did not decide differently from non-users concerning hypertension treatment decisions. Instead of focusing on the fact if GPs use guidelines or not, we as a scientific community should put an emphasis on what guidelines suggest in frail and oldest-old patients.

Quality of medicines for life-threatening pregnancy complications in low- and middle-income countries: A systematic review

by Maria Regina Torloni, Mercedes Bonet, Ana Pilar Betrán, Carolina C. Ribeiro-do-Valle, Mariana Widmer


There are concerns about the quality of medicines available in low- and middle-income countries (LMIC) to manage hemorrhage, pre-eclampsia/eclampsia and sepsis. We aimed to identify, critically appraise, and synthesize the findings of studies on the quality of these three types of medicines available in LMIC.


This systematic review searched Medline, EMBASE and LILACS (from inception to 25 May 2020) for studies on the quality of selected medicines available in LMIC that provided at least the amount of active pharmaceutical ingredient. We contacted study authors for additional information. We excluded simulation studies. We used the MEDQUARG tool to assess study quality. The main outcome was the prevalence of failed samples.


We identified 9699 unique citations and included 34 studies (3159 samples from 40 countries) in the review. Most studies (65%) had low quality (scores Conclusions

There is a widespread problem with the quality of medicines used to manage life-threatening maternal conditions in LMIC. This can be a contributing factor to high maternal mortality rates in these regions.

Inflammation changes the expression of neuropeptide Y receptors in the pig myometrium and their role in the uterine contractility

by Barbara Jana, Jarosław Całka, Katarzyna Palus

In the experiment the influence of inflammation on neuropeptide Y (NPY) receptor subtype 1 (Y1Rs) and 2 (Y2Rs) expression pattern in the gilt myometrium and NPY effect alone or with Y1Rs and Y2Rs antagonists on contractility of an inflamed uterus were recognized. On Day 3 of the estrous cycle, either E.coli suspension (E.coli group) or saline (SAL group) were administered into uterine horns. In the control gilts (CON group), only laparotomy was carried out. Eight days later, E.coli treatment evoked severe acute endometritis, significantly reduced Y1Rs mRNA and protein expression and increased Y2Rs protein expression in myometrium in relation to the CON and SAL groups. Compared to period before NPY application, NPY (10−7 M) significantly reduced amplitude in myometrium and endometrium/myometrium and frequency in myometrium of the CON and SAL groups and amplitude in endometrium/myometrium and frequency in strips of the E.coli group. In this group, after using NPY (10−7 M), the amplitude rose significantly in both kinds of strips, while frequency fell in endometrium/myometrium in relation to the SAL group. In the CON and SAL groups, NPY (10−7 M) with Y1Rs antagonist significantly increased the amplitude in endometrium/myometrium, while with Y2Rs antagonist caused a rise in myometrium. In the E.coli group after using Y1Rs or Y2Rs antagonist and NPY (10−7 M) amplitude did not significantly change in endometrium/myometrium, and this parameter was significantly lower after using the NPY and Y1Rs antagonist than in other groups. Y1Rs antagonist and NPY (10−8, 10−7 M) significantly increased frequency in endometrium/myometrium of the CON and SAL groups. In the E.coli group, Y1Rs or Y2Rs antagonists and NPY (10−7 M) significantly increased frequency in myometrium and it was significantly higher than in the CON group. Inflammation changes Y1Rs and Y2Rs expression in myometrium of the inflamed pig uterus and NPY reduces this organ contractility by Y1Rs and Y2Rs.

Analysis of the fetal cardio-electrohysterographic coupling at the third trimester of gestation in healthy women by Bivariate Phase-Rectified Signal Averaging

by José Eduardo Montero-Nava, Adriana Cristina Pliego-Carrillo, Claudia Ivette Ledesma-Ramírez, Miguel Ángel Peña-Castillo, Juan Carlos Echeverría, Gustavo Pacheco-López, José Javier Reyes-Lagos


The fetal cardio-electrohysterographic coupling (FCEC) is defined as the influence of the uterine electrical activity on fetal heart rate. FCEC has been mainly evaluated by visual analysis of cardiotocographic data during labor; however, this physiological phenomenon is poorly explored during the antenatal period. Here we propose an approach known as Bivariate Phase-Rectified Signal Averaging analysis (BPRSA) to assess such FCEC in the late third trimester of low-risk pregnancies. We hypothesized that BPRSA is a more reliable measure of FCEC than visual analysis and conventional measures such as cross-correlation, coherence, and cross-sample entropy. Additionally, by using BPRSA it is possible to detect FCEC even from the third trimester of pregnancy.

Material and methods

Healthy pregnant women in the last third trimester of pregnancy (36.6 ± 1.8 gestational weeks) without any clinical manifestation of labor were enrolled in the Maternal and Childhood Research Center (CIMIGen), Mexico City (n = 37). Ten minutes of maternal electrohysterogram (EHG) and fetal heart rate (FHR) data were collected by a transabdominal non-invasive device. The FCEC was quantified by the coefficient of coherence, the maximum normalized cross-correlation, and the cross-sample entropy obtained either from the EHG and FHR raw signals or from the corresponding BPRSA graphs.


We found that by using BPRSA, the FCEC was detected in 92% cases (34/37) compared to 48% cases (18/37) using the coefficient of coherence between the EHG and FHR raw signals. Also, BPRSA indicated FCEC in 82% cases (30/37) compared to 30% cases (11/37) using the maximum normalized cross-correlation. By comparing the analyses, the BPRSA evidenced higher FCEC in comparison to the coupling estimated from the raw EHG and FHR signals.


Our results support the consideration that in the third trimester of pregnancy, the fetal heart rate is also influenced by uterine activity despite the emerging manifestation of this activity before labor. To quantify FCEC, the BPRSA can be applied to FHR and EHG transabdominal signals acquired in the third trimester of pregnancy.

Age-related differences in correction behavior for unintended acceleration

by Kunihiro Hasegawa, Motohiro Kimura, Yuji Takeda

Although unintended acceleration caused by pedal misapplication is a cause of traffic accidents, fatal accidents may be avoided if drivers realize their error immediately and quickly correct how they are stepping on the pedal. This correction behavior may decline with age because the rate of fatal accidents is fairly higher for older adults than for younger adults. To investigate this possibility, the present study recruited older adults (n = 40, age range = 67–81 years) as well as younger adults (n = 40, age range = 18–32 years). In this study, they performed a pedal stepping task during which they were required to stop the simulated vehicle as quickly as possible when a red signal was presented on a monitor. During most trials, the vehicle decelerated/stopped when the brake pedal was applied in a normal manner. In a few trials, however, stepping on the brake pedal resulted in sudden acceleration of the vehicle (i.e., the occurrence of the unintended acceleration); when this occurred, the participants had to release the pedal and re-step on another pedal to decelerate/stop the vehicle as quickly as possible. We focused on the age-related differences of the reaction latencies during three time periods: from the appearance of the red signal on the screen until stepping on the pedal (Period 1), from stepping on the pedal until the release of the pedal (Period 2), and from the release of the pedal until re-stepping of another pedal (Period 3). The results showed that there was no age-related difference in the latency of Period 1, p = .771, whereas those of Periods 2 and 3 were longer for the older adults (ps

Maternal, paternal, and other caregivers’ stimulation in low- and- middle-income countries

by Jorge Cuartas, Joshua Jeong, Catalina Rey-Guerra, Dana Charles McCoy, Hirokazu Yoshikawa

Background and objectives

Globally, studies have shown associations between maternal stimulation and early child development. Yet, little is known about the prevalence of paternal and other caregivers’ stimulation practices, particularly in low- and- middle-income countries (LMICs).


Data from the Multiple Indicators Cluster Survey (MICS) and the Demographic and Health Survey (DHS) were combined across 62 LMICs (2010–2018). The sample included 205,150 mothers of children aged 3 and 4 years. High levels of stimulation were defined as caregiver engagement in at least 4 out of 6 possible activities with the child. The proportion of mothers, fathers, and other caregivers providing high levels of stimulation was calculated by country, region, and for the whole sample. Socioeconomic disparities within and between countries were estimated.


On average, 39.8% (95% CI 37.4 to 42.2) of mothers, 11.9% (95% CI 10.1 to 13.8) of fathers, and 20.7% (95% CI 18.4 to 23.0) of other adult caregivers provided high levels of stimulation. Stimulation varied by region, country income group, and Human Development Index (HDI), with higher levels of maternal and paternal–but not other caregivers’–stimulation in high-income and high-HDI countries. Within countries, stimulation levels were, on average, lower in the poorest relative to the richest households, and some but not all countries exhibited differences by child sex (i.e., boys vs. girls) or area (i.e., urban vs. rural).


Results suggest a need for intervention efforts that focus on increasing caregiver stimulation in LMICs, particularly for fathers and in low-income contexts.

Feasibility and acceptability of a milk and resistance exercise intervention to improve muscle function in community-dwelling older adults (MIlkMAN): Pilot study

by Antoneta Granic, Christopher Hurst, Lorelle Dismore, Emma Stevenson, Avan A. Sayer, Terry Aspray


Dietary protein supplementation combined with resistance exercise (RE) may counteract declines in muscle strength, mass, and function (sarcopenia), but the role of whole foods rich in protein, such as milk, is less well understood. In the MIlkMAN study, we aimed to examine the feasibility and acceptability of milk+RE as an intervention for muscle function in community-dwelling older adults, and provide exploratory pilot data for future substantive research in population at risk of sarcopenia.


In a parallel groups design, 30 older adults (71.7±3.6 years; 12 women) were randomised into three groups: WM (whole milk 3.6% fat)+RE, SM (skimmed milk 0.3% fat)+RE, and C (isocaloric carbohydrate drink)+RE. RE was performed twice-weekly over 6 weeks in a community gym, followed by the consumption of 500 ml of milk (~20 g protein) or carbohydrate drink immediately after exercise and a further 500 ml at home within the following 4–5 hours. The feasibility and acceptability of the study was determined by calculating recruitment and attendance rates, compliance with the intervention, rating participants’ experiences, and recording adverse health events.


The response rate was 49% (out of 400 invitations sent), and the recruitment rate was 73.2% (30 participants recruited out of 41 screened for eligibility). Twenty-nine participants completed the intervention—an attendance rate of 97.1%; 89.7% rated their experience as ‘excellent’/very good’. Compliance with taking the drinks was 97.1% (WM), 98.3% (SM), and 95.0% (C); 93.1% rated their drink intake as ‘easy’/’very easy’ with no adverse effects. Collection of exploratory pilot data to inform future trials was successful. Mean change in grip strength, 5-chair rises, and gait speed were 0.9±3.4 kg, 1.8±2.2 s, 0.1±0.1 m/s, respectively with no differences between the groups.


This community-based milk+RE intervention was feasible and acceptable to older adults. The study successfully collected pilot data for future substantive research.

Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody

by Qing Lin, Shari A. Price, John T. Skinner, Bin Hu, Chunling Fan, Kazuyo Yamaji-Kegan, Roger A. Johns

Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies.

Using liquid chromatography mass spectrometry (LC-MS) to assess the effect of age, high-fat diet, and rat strain on the liver metabolome

by Greg Boyce, Mohammad Shoeb, Vamsi Kodali, Terence Meighan, Jenny R. Roberts, Aaron Erdely, Michael Kashon, James M. Antonini

The goal of this study was to use liquid chromatography mass spectrometry to assess metabolic changes of two different diets in three distinct rat strains. Sprague-Dawley, Fischer 344, and Brown-Norway male rats were maintained on a high-fat, or regular diet for 24 weeks. Liver tissue was collected at 4, 12, and 24 weeks to assess global small molecule metabolite changes using high resolution accurate mass spectrometry coupled to ultra-high-performance liquid chromatography. The results of the global metabolomics analysis revealed significant changes based on both age and diet within all three strains. Principal component analysis revealed that the influence of diet caused a greater variation in significantly changing metabolites than that of age for the Brown Norway and Fisher 344 strains, whereas diet had the greatest influence in the Sprague Dawley strain only at the 4-week time point. As expected, metabolites involved in lipid metabolism were changed in the animals maintained on a high fat diet compared to the regular diet. There were also significant changes observed in the concentration of Tri carboxylic acid cycle intermediates that were extracted from the liver of all three strains based on diet. The results of this study showed that a high fat diet caused significant liver and metabolic changes compared to a regular diet in multiple rat strains. The inbred Fisher 344 and Brown Norway rats were more metabolically sensitive to the diet changes than outbred Sprague Dawley strain. The study also showed that age, as was the case for Sprague Dawley, is an important variable to consider when assessing metabolic changes.

Prevalence of clinically manifested drug interactions in hospitalized patients: A systematic review and meta-analysis

by Tâmara Natasha Gonzaga de Andrade Santos, Givalda Mendonça da Cruz Macieira, Bárbara Manuella Cardoso Sodré Alves, Thelma Onozato, Geovanna Cunha Cardoso, Mônica Thaís Ferreira Nascimento, Paulo Ricardo Saquete Martins-Filho, Divaldo Pereira de Lyra Jr., Alfredo Dias de Oliveira Filho


This review aims to determine the prevalence of clinically manifested drug-drug interactions (DDIs) in hospitalized patients.


PubMed, Scopus, Embase, Web of Science, and Lilacs databases were used to identify articles published before June 2019 that met specific inclusion criteria. The search strategy was developed using both controlled and uncontrolled vocabulary related to the following domains: “drug interactions,” “clinically relevant,” and “hospital.” In this review, we discuss original observational studies that detected DDIs in the hospital setting, studies that provided enough data to allow us to calculate the prevalence of clinically manifested DDIs, and studies that described the drugs prescribed or provided DDI adverse reaction reports, published in either English, Portuguese, or Spanish.


From the initial 5,999 articles identified, 10 met the inclusion criteria. The pooled prevalence of clinically manifested DDIs was 9.2% (CI 95% 4.0–19.7). The mean number of medications per patient reported in six studies ranged from 4.0 to 9.0, with an overall average of 5.47 ± 1.77 drugs per patient. The quality of the included studies was moderate. The main methods used to identify clinically manifested DDIs were evaluating medical records and ward visits (n = 7). Micromedex® (27.7%) and Lexi-Comp® (27.7%) online reference databases were commonly used to detect DDIs and none of the studies evaluated used more than one database for this purpose.


This systematic review showed that, despite the significant prevalence of potential DDIs reported in the literature, less than one in ten patients were exposed to a clinically manifested drug interaction. The use of causality tools to identify clinically manifested DDIs as well as clinical adoption of DDI lists based on actual adverse outcomes that can be identified through the implementation of real DDI notification systems is recommended to reduce the incidence of alert fatigue, enhance decision-making for DDI prevention or resolution, and, consequently, contribute to patient safety.

Beak and feather disease virus (BFDV) prevalence, load and excretion in seven species of wild caught common Australian parrots

by Johanne M. Martens, Helena S. Stokes, Mathew L. Berg, Ken Walder, Shane R. Raidal, Michael J. L. Magrath, Andy T. D. Bennett

Pathogens pose a major risk to wild host populations, especially in the face of ongoing biodiversity declines. Beak and feather disease virus (BFDV) can affect most if not all members of one of the largest and most threatened bird orders world-wide, the Psittaciformes. Signs of disease can be severe and mortality rates high. Its broad host range makes it a risk to threatened species in particular, because infection can occur via spill-over from abundant hosts. Despite these risks, surveillance of BFDV in locally abundant wild host species has been lacking. We used qPCR and haemagglutination assays to investigate BFDV prevalence, load and shedding in seven abundant host species in the wild in south-east Australia: Crimson Rosellas (Platycercus elegans), Eastern Rosellas (Platycercus eximius), Galahs (Eolophus roseicapillus), Sulphur-crested Cockatoos (Cacatua galerita), Blue-winged Parrots (Neophema chrysostoma), Rainbow Lorikeets (Trichoglossus moluccanus) and Red-rumped Parrots (Psephotus haematonotus). We found BFDV infection in clinically normal birds in six of the seven species sampled. We focused our analysis on the four most commonly caught species, namely Crimson Rosellas (BFDV prevalence in blood samples: 41.8%), Sulphur-crested Cockatoos (20.0%), Blue-winged Parrots (11.8%) and Galahs (8.8%). Species, but not sex, was a significant predictor for BFDV prevalence and load. 56.1% of BFDV positive individuals were excreting BFDV antigen into their feathers, indicative of active viral replication with shedding. Being BFDV positive in blood samples predicted shedding in Crimson Rosellas. Our study confirms that BFDV is endemic in our study region, and can inform targeted disease management by providing comparative data on interspecies variation in virus prevalence, load and shedding.

Attitude and beliefs about the social environment associated with chemsex among MSM visiting STI clinics in the Netherlands: An observational study

by Ymke J. Evers, Jill J. H. Geraets, Geneviève A. F. S. Van Liere, Christian J. P. A. Hoebe, Nicole H. T. M. Dukers-Muijrers


Drug use during sex, ‘chemsex’, is common among men who have sex with men (MSM) and related to sexual and mental health harms. This study assessed associations between chemsex and a wide range of determinants among MSM visiting STI clinics to increase understanding of characteristics and beliefs of MSM practicing chemsex.


In 2018, 785 MSM were recruited at nine Dutch STI clinics; 368 (47%) fully completed the online questionnaire. All participants reported to have had sex in the past six months. Chemsex was defined as using cocaine, crystal meth, designer drugs, GHB/GBL, ketamine, speed or XTC/MDMA during sex in the past six months. Associations between chemsex and psychosocial determinants, socio-demographics, sexual behaviour and using tobacco or alcohol were assessed by multivariable logistic regression analyses.


Chemsex was reported by 44% of MSM (161/368) and was not associated with socio-demographics. Independent determinants were ‘believing that the majority of friends/sex partners use drugs during sex’ (descriptive norm) (aOR: 1.95, 95%CI: 1.43–2.65), ‘believing that sex is more fun when using drugs’ (attitude) (aOR: 2.06, 95%CI: 1.50–2.84), using tobacco (aOR: 2.65, 95%CI: 1.32–5.32), multiple sex partners (aOR: 2.69, 95%CI: 1.21–6.00), group sex (aOR: 4.65, 95%CI: 1.54–14.05) and using online dating platforms (aOR: 2.73, 95%CI: 1.13–6.62).


MSM are likely to find themselves in distinct social networks where it is the norm to use drugs when having sex and pleasure is linked to chemsex. Health services should acknowledge the social influence and pleasurable experiences to increase acceptability of strategies aimed at minimizing the possible harms of chemsex.