bluuebunny/crossref_metadata_2025 huggingface dataset:
The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial
Authors: Ndhlovu Chiratidzo E. , Kouamou Vinie , Nyamayaro Primrose , Dougherty Leanne , Willis Nicola , Ojikutu Bisola O. , Makadzange A. Tariro
Published: June 2021

Background

Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF).

Methods

We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing.

Results

The participants’ median (interquartile range (IQR)) age was 18.1 (IQR: 15.1–20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146).

Conclusion

A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART.

Trial registration: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441
Women’s voices on social media: the advent of feminist epidemiology?
Authors: Miani Céline , Namer Yudit
Published: June 2021

Background

Social media have in recent years challenged the way in which research questions are formulated in epidemiology and medicine, and in particular when it comes to women’s health. They have contributed to the emergence of ‘new’ public health topics (e.g. gynaecological and obstetric violence, long-Covid), the unearthing of testimonials of medical injustice, and in some cases, the creation of new evidence and changes in medical practice.

Main text

From a theoretical and methodological perspective, we observe two powerful mechanisms at play on social media, which can facilitate the implementation of feminist epidemiological research and address so-called anti-feminist bias: social media as a ‘third’ space and the power of groups. Social media posts can be seen as inhabiting a third space, akin to what is said off the record or in-between doors, at the end of a therapy session. Researchers somehow miss the opportunity to use the third spaces that people occupy. Similarly, another existing space that researchers are seldom interested in are peer-groups. Peer-groups are the ideal terrain to generate bottom-up research priorities. To some extent, their on-line versions provide a safe and emancipatory space, accessible, transnational, and inclusive. We would argue that this could bring feminist epidemiology to scale.

Conclusion

Given the emancipatory power of social media, we propose recommendations and practical implications for leveraging the potential of online-sourced feminist epidemiology at different stages of the research process (from design to dissemination), and for increasing synergies between researchers and the community. We emphasise that attention should be paid to patriarchal sociocultural contexts and power dynamics, the mitigation of risks for political recuperation and stigmatisation, and the co-production of respectful discourse on studied populations.
Malondialdehyde concentrations in obsessive–compulsive disorder: a systematic review and meta-analysis
Authors: Mohammadi Amir Hossein , Balandeh Ebrahim , Milajerdi Alireza
Published: June 2021

Background

This meta-analysis aimed to investigate serum and plasma malondialdehyde (MDA) levels in patients with obsessive–compulsive disorder (OCD) in comparison to healthy controls.

Methods

Following the PRISMA protocol, we searched for the relevant studies through the databases of Scopus, PubMed, Google Scholar, and web of science until September 2019 with no time restriction. Overall, nine studies were included in the current meta-analysis. Data were pooled using a random-effects model; in addition, standard mean difference (SMD) and/or weight mean difference (WMD) was calculated. Cochran’s Q test and I-square (I2) statistics were used to evaluate between-study heterogeneity. The Newcastle–Ottawa scale (NOS) was used to evaluate the quality of the included studies. Statistical analyses were done using the STATA version 14.

Results

Our systematic review included nine case–control studies (including 367 cases and 337 controls). Pooling findings from these studies showed a significantly higher MDA level in OCD patient compared to control groups (SMD = 1.62; 95% CI [0.53, 2.72]; I2 = 96.9%; Pheterogeneity (Ph) < 0.001). This finding remained unchanged among studies which reported MDA in the same unit (WMD = 1.93; 95% CI [0.27, 3.59]; I2 = 99.2%; Ph < 0.001). Subgroup analysis by the study location and sample size revealed findings that were also significant.

Conclusion

We found that MDA levels are higher in OCD patients than healthy controls. This finding highlights the importance of inflammatory responses in OCD patients that should be considered for future investigations. Further studies are recommended to expand current knowledge on this issue.
Rapid identification of mutations caused by fast neutron bombardment in Medicago truncatula
Authors: Du Huan , Jiao Zhicheng , Liu Junjie , Huang Wei , Ge Liangfa
Published: June 2021

Background

Fast neutron bombardment (FNB) is a very effective approach for mutagenesis and has been widely used in generating mutant libraries in many plant species. The main type of mutations of FNB mutants are deletions of DNA fragments ranging from few base pairs to several hundred kilobases, thus usually leading to the null mutation of genes. Despite its efficiency in mutagenesis, identification of the mutation sites is still challenging in many species. The traditional strategy of positional cloning is very effective in identifying the mutation but time-consuming. With the availability of genome sequences, the array-based comparative genomic hybridization (CGH) method has been developed to detect the mutation sites by comparing the signal intensities of probes between wild-type and mutant plants. Though CGH method is effective in detecting copy number variations (CNVs), the resolution and coverage of CGH probes are not adequate to identify mutations other than CNVs.

Results

We report a new strategy and pipeline to sensitively identify the mutation sites of FNB mutants by combining deep-coverage whole-genome sequencing (WGS), polymorphism calling, and customized filtering in Medicago truncatula. Initially, we performed a bulked sequencing for a FNB white nodule (wn) mutant and its wild-type like plants derived from a backcross population. Following polymorphism calling and filtering, validation by manual check and Sanger sequencing, we identified that SymCRK is the causative gene of white nodule mutant. We also sequenced an individual FNB mutant yellow leaves 1 (yl1) and wild-type plant. We identified that ETHYLENE-DEPENDENT GRAVITROPISM-DEFICIENT AND YELLOW-GREEN 1 (EGY1) is the candidate gene for M. truncatula yl1 mutant.

Conclusion

Our results demonstrated that the method reported here is rather robust in identifying the mutation sites for FNB mutants.
68Ga-NOTA-Evans Blue PET/CT findings in lymphangioleiomyomatosis compared with 99mTC-ASC lymphoscintigraphy: a prospective study
Authors: Hou Guozhu , Jiang Yuanyuan , Xu Wenshuai , Zhu Zhaohui , Huo Li , Chen Xiaoyuan , Li Fang , Xu Kai-Feng , Cheng Wuying
Published: June 2021

Background

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease characterized by cystic lung disease and extrapulmonary manifestations, including lymphatic system disorder. The objective of this study was to investigate the findings of 68Ga-NOTA-Evans Blue (NEB) PET/CT in LAM and compare it with that of 99mTc-ASC lymphoscintigraphy.

Methods

Ten patients diagnosed with LAM according to the American Thoracic Society/Japanese Respiratory Society guidelines for LAM were recruited in this study. PET/CT acquisition was performed at 20 to 40 min after subcutaneous injection of 68Ga-NEB into the first interdigital spaces of both feet (0.3 ml, 37 MBq/foot). All subjects also underwent 99mTc-antimony sulfide colloid (ASC) lymphoscintigraphy within a week for comparison.

Results

68Ga-NEB PET/CT displayed various lymphatic system abnormalities in 10 (100%) of 10 patients. These included pulmonary lymphatic abnormalities in 10 (100%) of 10 patients, enlarged lymph nodes in 5 (50%), lymphangioleiomyomas in 2 (20%), dilation of the lumbar trunk and/or iliac lymph vessels in 5 (50%), thoracic duct dilation in 2 (20%), chylous effusion in 1 (10%). For pulmonary lymphatic abnormalities, the positive rates of 68Ga-NEB PET/CT and 99mTc-ASC lymphoscintigraphy were 100% (10/10) and 10% (1/10), respectively (P < 0.001). As for the 7 patients with extrapulmonary lymphatic manifestations, 68Ga-NEB PET/CT also presented more information than 99mTc-ASC lymphoscintigraphy.

Conclusion

68Ga-NEB PET/CT visualized pulmonary lymphatic abnormality and displayed extrapulmonary lymphatic system disorders of LAM, and might play a role in the diagnosis and evaluation of the disease. 68Ga-NEB PET/CT is advantageous over conventional 99mTc-ASC lymphoscintigraphy in LAM by providing more detailed information of lymphatic dysfunction.
Reducing the diagnostic delay in Antiphospholipid Syndrome over time: a real world observation
Authors: Radin Massimo , Foddai Silvia Grazietta , Barinotti Alice , Cecchi Irene , Rubini Elena , Sciascia Savino , Roccatello Dario
Published: June 2021

Background

Antiphospholipid Syndrome (APS) is a rare autoimmune disorder with an estimated prevalence of 40–50 cases per 100.000 persons. Patients suffering from low prevalence diseases are more likely to face diagnostic challenges, given the limited knowledge of most clinicians. The main aim of this study was to investigate the time between symptoms occurrence and the diagnosis of APS patients using the Piedmont and Aosta Valley Rare Disease Registry. Secondly, to evaluate the individual impact of the diagnostic gap by gathering patients’ personal experiences through a self-administered questionnaire.

Results

Data from the Piedmont and Aosta Valley Rare Disease Registry was used. In addition, personal experiences were analyzed through a self-administered questionnaire. A total of 740 APS patients included in the Piedmont and Aosta Valley Rare Disease Registry were analyzed. Diagnostic delay (as defined by time between symptoms’ occurrence and the diagnosis of APS) was significantly reduced over time. In particular, when comparing the diagnostic delay between patients diagnosed between 1983 and 1999 and patients diagnosed between 2000 and 2015, we found a significant statistical difference (Mann-Whithey U Test; mean rank 1216.6 vs. 1066.9, respectively; p < 0.0001). When analyzing the self-administered questionnaires, patients with a perception of having suffered for a diagnostic delay had a higher prevalence of symptoms suggestive of an autoimmune condition but not highly suggestive of APS (45%), followed by “extra criteria” APS manifestation (30%) and by thrombotic events (25%). The first clinical manifestation of patients who did not have the perception of having suffered a diagnostic delay was thrombotic events (45.5%), followed by autoimmune manifestation not linked to APS (45.5%), and “extra criteria” APS manifestations (9%).

Conclusions

While the diagnostic delay of APS has been reduced during the last years, the time between symptoms occurrence and the diagnosis of rare diseases still represents a critical issue to be addressed in order to prevent major complications.
Recruiting hard-to-reach pregnant women at high psychosocial risk: strategies and costs from a randomised controlled trial
Authors: MacLachlan Alice , Crawford Karen , Shinwell Shona , Nixon Catherine , Henderson Marion
Published: June 2021

Background

Recruiting participants to randomised controlled trials (RCTs) is often challenging, particularly when working with socially disadvantaged populations who are often termed ‘hard-to-reach’ in research. Here we report the recruitment strategies and costs for the Trial for Healthy Relationship Initiatives in the Very Early years (THRIVE), an RCT evaluating two group-based parenting interventions for pregnant women.

Methods

THRIVE aimed to recruit 500 pregnant women with additional health and social care needs in Scotland between 2014 and 2018. Three recruitment strategies were employed: (1) referrals from a health or social care practitioner or voluntary/community organisation (practitioner-led referral), (2) direct engagement with potential participants by research staff (researcher-led recruitment) and (3) self-referral in response to study advertising (self-referral). The number of referrals and recruited participants from each strategy is reported along with the overall cost of recruitment. The impact of recruitment activities and the changes in maternity policy/context on recruitment throughout the study are examined.

Results

THRIVE received 973 referrals: 684 (70%) from practitioners (mainly specialist and general midwives), 273 (28%) from research nurses and 16 (2%) self-referrals. The time spent in antenatal clinics by research nurses each month was positively correlated with the number of referrals received (r = 0.57; p < 0.001). Changes in maternity policies and contexts were reflected in the number of referrals received each month, with both positive and negative impacts throughout the trial. Overall, 50% of referred women were recruited to the trial. Women referred via self-referral, THRIVE research nurses and specialist midwives were most likely to go on to be recruited (81%, 58% and 57%, respectively). Key contributors to recruitment included engaging key groups of referrers, establishing a large flexible workforce to enable recruitment activities to adapt to changes in context throughout the study and identifying the most appropriate setting to engage with potential participants. The overall cost of recruitment was £377 per randomised participant.

Conclusions

Recruitment resulted from a combination of all three strategies. Our reflections on the successes and challenges of these strategies highlight the need for recruitment strategies to be flexible to adapt to complex interventions and real-world challenges. These findings will inform future research in similar hard-to-reach populations.

Trial registration

International Standard Randomised Controlled Trials Number Registry ISRCTN21656568. Retrospectively registered on 28 February 2014
Indoor residual spraying practices against Triatoma infestans in the Bolivian Chaco: contributing factors to suboptimal insecticide delivery to treated households
Authors: Gonçalves Raquel , Logan Rhiannon A. E. , Ismail Hanafy M. , Paine Mark J. I. , Bern Caryn , Courtenay Orin
Published: June 2021

Background

Indoor residual spraying (IRS) of insecticides is a key method to reduce vector transmission of Trypanosoma cruzi, causing Chagas disease in a large part of South America. However, the successes of IRS in the Gran Chaco region straddling Bolivia, Argentina, and Paraguay, have not equalled those in other Southern Cone countries.

Aims

This study evaluated routine IRS practices and insecticide quality control in a typical endemic community in the Bolivian Chaco.

Methods

Alpha-cypermethrin active ingredient (a.i.) captured onto filter papers fitted to sprayed wall surfaces, and in prepared spray tank solutions, were measured using an adapted Insecticide Quantification Kit (IQK™) validated against HPLC quantification methods. The data were analysed by mixed-effects negative binomial regression models to examine the delivered insecticide a.i. concentrations on filter papers in relation to the sprayed wall heights, spray coverage rates (surface area / spray time [m2/min]), and observed/expected spray rate ratios. Variations between health workers and householders’ compliance to empty houses for IRS delivery were also evaluated. Sedimentation rates of alpha-cypermethrin a.i. post-mixing of prepared spray tanks were quantified in the laboratory.

Results

Substantial variations were observed in the alpha-cypermethrin a.i. concentrations delivered; only 10.4% (50/480) of filter papers and 8.8% (5/57) of houses received the target concentration of 50 mg ± 20% a.i./m2. The delivered concentrations were not related to those in the matched spray tank solutions. The sedimentation of alpha-cypermethrin a.i. in the surface solution of prepared spray tanks was rapid post-mixing, resulting in a linear 3.3% loss of a.i. content per minute and 49% loss after 15 min. Only 7.5% (6/80) of houses were sprayed at the WHO recommended rate of 19 m2/min (± 10%), whereas 77.5% (62/80) were sprayed at a lower than expected rate. The median a.i. concentration delivered to houses was not significantly associated with the observed spray coverage rate. Householder compliance did not significantly influence either the spray coverage rates or the median alpha-cypermethrin a.i. concentrations delivered to houses.

Conclusions

Suboptimal delivery of IRS is partially attributable to the insecticide physical characteristics and the need for revision of insecticide delivery methods, which includes training of IRS teams and community education to encourage compliance. The IQK™ is a necessary field-friendly tool to improve IRS quality and to facilitate health worker training and decision-making by Chagas disease vector control managers.

Graphical Abstract
Effects of task difficulty during practice on learning a dynamic balance task in healthy young adults: An intervention study
Authors: Schedler Simon , Leifeld Pascal , Seidel Tim , Brueckner Dennis , Muehlbauer Thomas
Published: June 2021

Objective

Cross-sectional studies reported increased postural sway during balance tasks with a high (e.g., unipedal stance on foam ground) compared to a low (e.g., unipedal stance on firm ground) level of task difficulty. Therefore, practicing/training balance tasks using high compared to low stimuli seems to be beneficial as it addresses larger adaptive reserves. Thus, the present study was performed to investigate the role of task difficulty during practice on learning a dynamic balance task in healthy young adults.

Results

During acquisition, both practice groups (“Easy” or “Difficult” task condition) significantly improved their performance (i.e., time in balance). Further, the statistical analysis of post-practice performance revealed a significant main effect of test (i.e., better performance under easy compared to difficult test conditions, irrespective of group) but not of group. Additionally, the Group × Test interaction did not reach the level of significance, indicating that learning a dynamic balance task did not depend on the practiced task condition.
The expression of miRNA-152-3p and miRNA-185 in tumor tissues versus margin tissues of patients with chemo-treated breast cancer
Authors: Safi Asma , Delgir Soheila , Ilkhani Khandan , Samei Azam , Mousavi Seyyed Reza , Zeynali-Khasraghi Zahra , Bastami Milad , Alivand Mohammad Reza
Published: June 2021

Objective

Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways.

Results

Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC (p-value ≥ 0.04407 and fold change = − 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.
Horn bud size of dairy-bred and suckler-bred calves at time of disbudding
Authors: Marquette Gabriela A. , McGee Mark , Fisher Andrew D. , Stanger Kelly , Argüello Anastasio , Earley Bernadette
Published: June 2021

Background

Hot-iron disbudding is a common management procedure to prevent horn growth in calves. The study objective was to examine effect of age, breed and sex on horn bud size of dairy-bred and suckler-bred calves at time of disbudding.

Results

The left and right horn bud size (diameter and height in mm) of 279 calves, including dairy-bred Holstein-Friesian (Male (M) = 88) and 191 suckler-bred (86 Charolais, CH; (M = 39, Female (F) = 47), 67 Limousin, LM; (M = 32, F = 35) and 38 Simmental, SI; (M = 22, F = 16) sired)) was measured using a digital calliper at time of disbudding. Calves were retrospectively assigned to two age categories at time of disbudding: 1), 14 to 28 days (d) old and 2), 29 to 60 d old. Holstein-Friesian M calves had a greater horn bud diameter (16.97 v.14.45 mm) and height (7.79 v. 5.00 mm) compared to suckler-bred M calves (P < 0.01), with no difference (P > 0.05) among the suckler-bred calves. Suckler-bred M calves had a greater horn bud diameter (14.46 vs 13.29 mm) and height (5.01 vs 3.88 mm) compared to suckler-bred F calves (P < 0.05).

The slopes of the lines of best fit show that horn bud diameter and height increased with age (P < 0.05) for HF, SI male and CH female calves while there was no relationship with age (P > 0.05) for CH and LM male calves, or for SI and LM female calves. Linear regression of age with diameter and with height for each breed and sex showed high variability in the data as indicated by R-squared values ranging from 0.003–0.41 indicating that in the case of the diameter and the height, the weight of the fitting effect was poor.

Conclusions

Calf age is not a good predictor of horn bud size and recommendations for the disbudding of calves should be based on horn bud size and not on age. The implications of these findings are that calves should be disbudded while horn development is still at the bud stage and when the bud is large enough to be easily palpable/visible, but not so large that disbudding could lead to severe tissue trauma.
Free convection inside a porous square cavity with convective boundary condition using spline functions
Authors: Micula Sanda , Pop Ioan
Published: June 2021

In this paper, we consider the problem of free convection in a square cavity filled with a porous medium with convective boundary condition on the left wall of the cavity. We first transform the governing equations transformed in terms of dimensionless variables and then solve them numerically using a cubic spline colocation method. We discuss the effects of two very important parameters, the Biot (Bi) and Rayleigh (Ra) numbers. We perform a comparison of the average Nusselt number $\overline{Nu}$

N
u

‾

at the hot wall with results from the open literature. We can notice that the comparison is very good, which gives us strong confidence that this cubic spline collocation method works very efficiently for such problems. We also state that the present problem has not been considered before by any researcher.
Construct new type solutions for the fractional Schrödinger equation
Authors: Lin Yuan , Liu Weiming
Published: June 2021

This paper is devoted to studying the following nonlinear fractional problem: $$ \textstyle\begin{cases} (-\Delta )^{s}u+u=K( \vert x \vert )u^{p},\quad u>0, x\in {\mathbb{R}}^{N}, \\ u(x)\in H^{s}({\mathbb{R}}^{N}), \end{cases} $$

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Handrub dispensers per acute care hospital bed: a study to develop a new minimum standard
Authors: Kuster Sabine , Roth Jan A. , Frei Reno , Meier Christoph A. , Dangel Marc , Widmer Andreas F.
Published: June 2021

Background

Accessibility to alcohol-based handrub (ABHR) dispenser is crucial to improve compliance to hand hygiene (HH), being offered as wall-mounted dispensers (ABHR-Ds), and/or pocket bottles. Nevertheless, information on the distribution and density of ABHR-Ds and their impact on HH have hardly been studied. Institutions such as the World Health Organisation or the Centers for Disease Control and Prevention do not provide guidance. The Robert-Koch-Institute (RKI) from Germany recommends an overall density of > 0.5 dispensers per patient bed. We aimed to investigate current conditions in hospitals to develop a standard on the minimal number of ABHR-D.

Methods

Between 07 and 09/2019, we applied a questionnaire to 178 hospitals participating in the Swissnoso National Surveillance Network to evaluate number and location of ABHR-Ds per bed in acute care hospitals, and compared the data with consumption and compliance with HH.

Results

110 of the 178 (62%) hospitals provided data representing approximately 20,000 hospital beds. 83% hospitals provided information on both the total number of ABHR-Ds and patient beds, with a mean of 2.4 ABHR-Ds per bed (range, 0.4–22.1). While most hospitals (84%) had dispensers located at the room entrance, 47% reported also locations near or at the bed. Additionally, pocket-sized dispensers (100 mL) are available in 97% of hospitals.

Conclusions

Swiss hospitals provide 2.4 dispensers per bed, much more than governmental recommendation. The first study on the number of ABHR-Ds in hospitals may help to define a minimal standard for national and international recommendations
Investigation of antibiotic susceptibilities of Brucella Strains isolated from various clinical samples in eastern Turkey
Authors: Gültekin Esra , Uyanık Muhammet Hamidullah , Albayrak Ayşe , Kılıç Selçuk
Published: June 2021

Background

Brucellosis is a worldwide zoonotic disease that causes serious public health problems. This study aimed to identify Brucella strains isolated from various clinical samples by conventional and molecular methods and to determine antimicrobial susceptibilities against doxycycline (DOX), streptomycin (STR), ciprofloxacin (CIP) and rifampicin (RIF) by the gradient strip (E test) test method.

Methods

A total of 87 Brucella strains isolated from various clinical specimens between 2004 and 2018 were included in this study. While four of the 87 strains included in the study were identified only at the genus level, the remaining 83 strains were identified at the species level by the Real-Time Multiplex PCR (M-RT-PCR) method and conventional methods were used for biotyping.

Results

According to molecular identification results, 83 strains were identified as B. melitensis by the M-RT-PCR method, with 82 strains identified as Brucella melitensis biovar (bv) 3 and one as B. melitensis bv 1 according to the conventional biotyping method. Among the antibiotics studied, CIP was found to be the most active agent according to the minimum inhibitory concentrations (MIC)90 values. This was followed by DOX and STR, respectively. While all of the isolates were sensitive to CIP, DOX and STR, 18 (20.7%) strains were found to be moderately susceptible to RIF, with the highest values of MIC50 and MIC90.

Conclusions

In our study, all strains were identified as B. melitensis. DOX, STR, CIP and RIF used in the treatment of brucellosis were found to be effective.
A systematic review on the implication of Candida in peri-implantitis
Authors: Lafuente-Ibáñez de Mendoza Irene , Cayero-Garay Amaia , Quindós-Andrés Guillermo , Aguirre-Urizar José Manuel
Published: June 2021

Background

Candidais a heterogeneous fungal genus. Subgingival sulcus is a refuge forCandida, which has already been related to the pathogenic inflammation of periodontitis. This work aims to review the presence ofCandidain the sulcular fluid surrounding dental implants and discuss its potential role in peri-implantitis.

Results

A bibliographical research was performed in PubMed, Scopus and Web of Science databases, with the keywordscandida, peri-implantitis, periimplantitis, “dental implant” and implant. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. At the end, nine observational studies were included, which analysed 400 dental implants with PI and 337 without peri-implantitis. Presence ofCandidawas assessed by traditional microbiological culture in blood agar or/and CHROMagar, though identification was also detected by quantitative real-time PCR, random amplified polymorphic DNA or ATB ID 32C. Dentate individuals and implants with peri-implantitis (range, 3–76.7%) had a bigger presence ofCandida.C.albicanswas the most isolated species, followed byCandida parapsilosis,Candida tropicalis, andCandida dubliniensis.

Conclusion

Candidais part of the microbiological profile of the peri-implant sulcular fluid. More studies are needed to compare the link betweenCandidaand other microorganisms and to discover the true role of these fungi in peri-implantitis.
A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering
Authors: Thitiset Thakoon , Damrongsakkul Siriporn , Yodmuang Supansa , Leeanansaksiri Wilairat , Apinun Jirun , Honsawek Sittisak
Published: June 2021

Background

A novel biodegradable scaffold including gelatin (G), chitooligosaccharide (COS), and demineralized bone matrix (DBM) could play a significant part in bone tissue engineering. The present study aimed to investigate the biological characteristics of composite scaffolds in combination of G, COS, and DBM for in vitro cell culture and in vivo animal bioassays.

Methods

Three-dimensional scaffolds from the mixture of G, COS, and DBM were fabricated into 3 groups, namely, G, GC, and GCD using a lyophilization technique. The scaffolds were cultured with mesenchymal stem cells (MSCs) for 4 weeks to determine biological responses such as cell attachment and cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, cell morphology, and cell surface elemental composition. For the in vivo bioassay, G, GC, and GCD, acellular scaffolds were implanted subcutaneously in 8-week-old male Wistar rats for 4 weeks and 8 weeks. The explants were assessed for new bone formation using hematoxylin and eosin (H&E) staining and von Kossa staining.

Results

The MSCs could attach and proliferate on all three groups of scaffolds. Interestingly, the ALP activity of MSCs reached the greatest value on day 7 after cultured on the scaffolds, whereas the calcium assay displayed the highest level of calcium in MSCs on day 28. Furthermore, weight percentages of calcium and phosphorus on the surface of MSCs after cultivation on the GCD scaffolds increased when compared to those on other scaffolds. The scanning electron microscopy images showed that MSCs attached and proliferated on the scaffold surface thoroughly over the cultivation time. Mineral crystal aggregation was evident in GC and greatly in GCD scaffolds. H&E staining illustrated that G, GC, and GCD scaffolds displayed osteoid after 4 weeks of implantation and von Kossa staining confirmed the mineralization at 8 weeks in G, GC, and GCD scaffolds.

Conclusion

The MSCs cultured in GCD scaffolds revealed greater osteogenic differentiation than those cultured in G and GC scaffolds. Additionally, the G, GC, and GCD scaffolds could promote in vivo ectopic bone formation in rat model. The GCD scaffolds exhibited maximum osteoinductive capability compared with others and may be potentially used for bone regeneration.
Stimulated Raman scattering simulation for imaging optimization
Authors: Zada Liron , Fokker Bart , Leslie Heather A. , Vethaak A. Dick , de Boer Johannes F. , Ariese Freek
Published: June 2021

Two simulation programs of a stimulated Raman scattering microscopy (SRS) imaging system with lock-in amplifier (LIA) detection were developed. SRS is an imaging technique based on the vibrational Raman cross-section as the contrast mechanism and enables fast, label-free imaging. Most SRS implementations are based on LIA detection of a modulated signal. However, building and operating such SRS set-ups still poses a challenge when selecting the LIA parameter settings for optimized acquisition speed or image quality. Moreover, the type of sample, e.g. a sparse sample vs. a densely packed sample, the required resolution as well as the Raman cross-section and the laser powers affect the parameter choice.

A simulation program was used to find these optimal parameters. The focal spot diameters of the individual lasers (pump and Stokes) were used to estimate the effective SRS signal focal spot and the (optical) spatial resolution. By calibrating the signal and noise propagation through an SRS system for a known molecule, we estimated the signal and noise input to the LIA. We used a low pass filter model to simulate the LIA behavior in order to find the optimal parameters (i.e. filter order and time constant).

Optimization was done for either image quality (expressed as contrast to noise ratio) or acquisition time. The targeted object size was first determined as a measure for the required resolution. The simulation output consisted of the LIA parameters, pixel dwell time and contrast to noise ratio.

In a second simulation we evaluated SRS imaging based on the same principles as the optimal setting simulation, i.e. the signals were propagated through an imaging system and LIA detection. The simulated images were compared to experimental SRS images of polystyrene beads.

Finally, the same software was used to simulate multiplexed SRS imaging. In this study we modeled a six-channel frequency-encoded multiplexed SRS system demodulated with six LIA channels. We evaluated the inter-channel crosstalk as a function of chosen LIA parameters, which in multiplex SRS imaging also needs to be considered.

These programs to optimize the contrast to noise ratio, acquisition speed, resolution and crosstalk will be useful for operating stimulated Raman scattering imaging setup, as well as for designing novel setups.
A single robust stability-indicating RP-HPLC analytical tool for apigenin quantification in bulk powder and in nanoliposomes: a novel approach
Authors: Shetti Priya , Jalalpure Sunil S.
Published: June 2021

Background

Apigenin (4′, 5, 7-trihydroxyflavone), a flavonoid, is present usually in fruits and vegetables possessing numerous biological properties like antioxidant, anti-viral, antibacterial, anti-inflammatory, and chemoprevention activity. So present study was aimed to prepare and characterize nanoliposomes of apigenin and estimate its encapsulation efficiency by stability-assisted reverse-phase (RP)-HPLC method.

Results

The stability indication of the RP-HPLC method developed for apigenin-loaded nanoliposomes was successfully demonstrated and parameters were mainly the retention time which was 4.21 min, limit of detection (LOD) 0.49 μg/mL, limit of quantification (LOQ) 1.48 μg/mL, and %relative standard deviation (RSD) less than 2%. Therefore, the stability indication of the developed reverse-phase HPLC method for apigenin-loaded nanoliposomes was demonstrated successfully and parameters like accuracy, linearity, LOD, LOQ, precision, and %RSD were within the limit range and found to be satisfactory.

Conclusion

The developed RP-HPLC method was found to be suitable for the quantification or estimation of apigenin with its stability in apigenin-loaded nanoliposomes, and this method will be a powerful tool in the future for the estimation of apigenin present in any pharmaceutical preparations.
Therapeutic Implications of Germline Testing in Patients With Advanced Cancers
Authors: Stadler Zsofia K. , Maio Anna , Chakravarty Debyani , Kemel Yelena , Sheehan Margaret , Salo-Mullen Erin , Tkachuk Kaitlyn , Fong Christopher J. , Nguyen Bastien , Erakky Amanda , Cadoo Karen , Liu Ying , Carlo Maria I. , Latham Alicia , Zhang Hongxin , Kundra Ritika , Smith Shaleigh , Galle Jesse , Aghajanian Carol , Abu-Rustum Nadeem , Varghese Anna , O'Reilly Eileen M. , Morris Michael , Abida Wassim , Walsh Michael , Drilon Alexander , Jayakumaran Gowtham , Zehir Ahmet , Ladanyi Marc , Ceyhan-Birsoy Ozge , Solit David B. , Schultz Nikolaus , Berger Michael F. , Mandelker Diana , Diaz Luis A. , Offit Kenneth , Robson Mark E.
Published: June 2021

PURPOSE

Tumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with advanced cancer.

METHODS

Patients with cancer undergoing tumor genomic profiling were prospectively consented for germline cancer predisposition gene analysis (2015-2019). In patients harboring germline likely pathogenic or pathogenic (LP/P) alterations, therapeutic actionability was classified using a precision oncology knowledge base. Patients with metastatic or recurrent cancer receiving germline genotype–directed therapy were determined.

RESULTS

Among 11,947 patients across > 50 malignancies, 17% (n = 2,037) harbored a germline LP/P variant. By oncology knowledge base classification, 9% (n = 1042) had an LP/P variant in a gene with therapeutic implications (4% level 1; 4% level 3B; < 1% level 4). BRCA1/2 variants accounted for 42% of therapeutically actionable findings, followed by CHEK2 (13%), ATM (12%), mismatch repair genes (11%), and PALB2 (5%). When limited to the 9,079 patients with metastatic or recurrent cancer, 8% (n = 710) harbored level 1 or 3B genetic findings and 3.2% (n = 289) received germline genotype–directed therapy. Germline genotype–directed therapy was received by 61% and 18% of metastatic cancer patients with level 1 and level 3B findings, respectively, and by 54% of BRCA1/2, 75% of mismatch repair, 43% of PALB2, 35% of RAD51C/D, 24% of BRIP1, and 19% of ATM carriers. Of BRCA1/2 patients receiving a poly(ADP-ribose) polymerase inhibitor, 45% (84 of 188) had tumors other than breast or ovarian cancer, wherein the drug, at time of delivery, was delivered in an investigational setting.

CONCLUSION

In a pan-cancer analysis, 8% of patients with advanced cancer harbored a germline variant with therapeutic actionability with 40% of these patients receiving germline genotype–directed treatment. Germline sequence analysis is additive to tumor sequence analysis for therapy selection and should be considered for all patients with advanced cancer.
Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants
Authors: Steffens Kristina E. , Wagner Karl G.
Published: June 2021

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.
Avidity and Outcomes of Radioiodine Therapy for Distant Metastasis of Distinct Types of Differentiated Thyroid Cancer
Authors: Simões-Pereira Joana , Mourinho Nádia , Ferreira Teresa C , Limbert Edward , Cavaco Branca Maria , Leite Valeriano
Published: June 2021

Context

The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response.

Objective

This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease.

Methods

A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response.

Results

RAIT avidity was independently associated with histology (P < .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (P = .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (P = .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS.

Conclusion

DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.
Hyperinsulinemic Compensation for Insulin Resistance Occurs Independent of Elevated Glycemia in Male Dogs
Authors: Ader Marilyn , Bergman Richard N
Published: June 2021

Insulin resistance engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of type 2 diabetes. The signal that heralds developing insulin resistance and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n = 58) were fed a hypercaloric, fat-supplemented diet for 6 weeks. Dogs underwent magnetic resonance imaging to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and insulin resistance at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6 to 8 pm) or nocturnal glycemia (2 to 4 am). Insulin resistance and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.
Heart rate and startle responses in diving, captive harbour porpoises (Phocoena phocoena) exposed to transient noise and sonar
Authors: Elmegaard Siri L. , McDonald Birgitte I. , Teilmann Jonas , Madsen Peter T.
Published: June 2021

Anthropogenic noise can alter marine mammal behaviour and physiology, but little is known about cetacean cardiovascular responses to exposures, despite evidence that acoustic stressors, such as naval sonars, may lead to decompression sickness. Here, we measured heart rate and movements of two trained harbour porpoises during controlled exposure to 6–9 kHz sonar-like sweeps and 40 kHz peak-frequency noise pulses, designed to evoke acoustic startle responses. The porpoises initially responded to the sonar sweep with intensified bradycardia despite unaltered behaviour/movement, but habituated rapidly to the stimuli. In contrast, 40 kHz noise pulses consistently evoked rapid muscle flinches (indicative of startles), but no behavioural or heart rate changes. We conclude that the autonomous startle response appears decoupled from, or overridden by, cardiac regulation in diving porpoises, whereas certain novel stimuli may motivate oxygen-conserving cardiovascular measures. Such responses to sound exposure may contribute to gas mismanagement for deeper-diving cetaceans.
The road to generating transplantable organs: from blastocyst complementation to interspecies chimeras
Authors: Zheng Canbin , Ballard Emily B. , Wu Jun
Published: June 2021

Growing human organs in animals sounds like something from the realm of science fiction, but it may one day become a reality through a technique known as interspecies blastocyst complementation. This technique, which was originally developed to study gene function in development, involves injecting donor pluripotent stem cells into an organogenesis-disabled host embryo, allowing the donor cells to compensate for missing organs or tissues. Although interspecies blastocyst complementation has been achieved between closely related species, such as mice and rats, the situation becomes much more difficult for species that are far apart on the evolutionary tree. This is presumably because of layers of xenogeneic barriers that are a result of divergent evolution. In this Review, we discuss the current status of blastocyst complementation approaches and, in light of recent progress, elaborate on the keys to success for interspecies blastocyst complementation and organ generation.