bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-plasmodial, Cytotoxic and Antioxidant Activities of Selected Ghanaian Medicinal Plants
Authors: Appiah-Opong Regina , Agyemang Kojo , Dotse Eunice , Atchoglo Philip , Owusu Kofi Baffour-Awuah , Aning Abigail , Sakyiamah Maxwell , Adegle Richard , Ayertey Frederick , Appiah Alfred Ampomah , Nyarko Alexander K.
Published: January 2022

Malaria affects about half of the world's population. The sub-Saharan African region is the most affected. Plant natural products have been a major source of antimalarial drugs; the first (quinine) and present (artemisinin) antimalarials are of natural product origin. Some secondary metabolites demonstrate adjuvant antioxidant effects and selective activity. The focus of this study was to investigate the anti-plasmodial activity, cytotoxicities and antioxidant properties of eight (8) Ghanaian medicinal plants. The anti-plasmodial activity was determined using the SYBR green assay and the tetrazolium-based colorimetric assay (MTT) was employed to assess cytotoxicity of extracts to human RBCs and HL-60 cells. Antioxidant potential of plant extracts was evaluated using Folin-Ciocalteu and superoxide dismutase assays. Phytochemical contstituents of the plant extracts were also assessed. All the extracts demonstrated anti-plasmodial activities at concentrations <50 μg/ml. Parkia clappertoniana and Terminalia ivorensis elicited the strongest anti-plasmodial activities with 50% inhibitory concentrations (IC50) of 1.13 μg/ml and 0.95 μg/ml, respectively. This is the first report on anti-plasmodial activities of Baphia nitida, Tabernaemontana crassa and Treculia Africana. T. Africana showed moderate anti-plasmodial activity with IC50 value of 6.62 µg/mL. Extracts of P. clappertoniana, T. Africana and T. ivorensis (0.4 mg/mL) showed >50% antioxidant effect (SOD). The extracts were not cytotoxicity towards RBCs at the concentration tested (200 μg/ml) but were weakly cytotoxic to HL-60 cell. Selectivity indices of most of the extracts were greater than 10. Our results suggest that most of the plant extracts have strong anti-plasmodial activity and antioxidant activity which warrants further investigations.
Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC)
Authors: Shaffer Rebecca , Thurman Angela John , Ronco Lucienne , Cadavid Diego , Raines Shane , Kim So Hyun
Published: January 2022

Background

Social communication is a key area of difficulty in fragile X syndrome (FXS) and there are not yet adequate outcome measurement tools. Appropriate outcome measures for FXS have been identified as a key area of research interest in order to evaluate future therapeutic trials. The Brief Observation of Social Communication Change-Minimally Verbal (BOSCC-MV), an outcome measure with strong psychometrics developed for autism spectrum disorder, has promise as an outcome measure to assess social communication change with FXS participants.

Methods

We examined the BOSCC-MV via central coders in this multi-site-trial to assess its appropriateness for FXS. Eighteen minimally verbal males ages 3–12 years were enrolled and assessed on two consecutive days and 7 participants completed a third visit 6 months later. We examined test-retest reliability, inter-rater reliability, and both convergent and divergent validity with standard clinical measures including the Autism Diagnostic and Observation Schedule-2, Vineland 3, Social Responsiveness Scale, and the Aberrant Behavior Checklist.

Results

The BOSCC-MV in FXS demonstrated strong inter-rater and test-retest reliability, comparable to previous trials in idiopathic ASD. Strong convergent validity was found with Autism Diagnostic Observation Schedule-2 and Vineland-3. Divergent validity was demonstrated between BOSCC-MV and unrelated measures.

Conclusions

The BOSCC-MV shows promise as a FXS social communication outcome measure, warranting further large-scale evaluation.
Molecular mechanism of mulberry response to drought stress revealed by complementary transcriptomic and iTRAQ analyses
Authors: Li Ruixue , Su Xueqiang , Zhou Rong , Zhang Yuping , Wang Taichu
Published: January 2022

Background

The use of mulberry leaves has long been limited to raising silkworms, but with the continuous improvement of mulberry (Morus alba) resource development and utilization, various mulberry leaf extension products have emerged. However, the fresh leaves of mulberry trees have a specific window of time for picking and are susceptible to adverse factors, such as drought stress. Therefore, exploring the molecular mechanism by which mulberry trees resist drought stress and clarifying the regulatory network of the mulberry drought response is the focus of the current work.

Results

In this study, natural and drought-treated mulberry grafted seedlings were used for transcriptomic and proteomic analyses (CK vs. DS9), aiming to clarify the molecular mechanism of the mulberry drought stress response. Through transcriptome and proteome sequencing, we identified 9889 DEGs and 1893 DEPs enriched in stress-responsive GO functional categories, such as signal transducer activity, antioxidant activity, and transcription regulator activity. KEGG enrichment analysis showed that a large number of codifferentially expressed genes were enriched in flavonoid biosynthesis pathways, hormone signalling pathways, lignin metabolism and other pathways. Through subsequent cooperation analysis, we identified 818 codifferentially expressed genes in the CK vs. DS9 comparison group, including peroxidase (POD), superoxide dismutase (SOD), aldehyde dehydrogenase (ALDHs), glutathione s-transferase (GST) and other genes closely related to the stress response. In addition, we determined that the mulberry geneMaWRKYIII8(XP_010104968.1) underwent drought- and abscisic acid (ABA)-induced expression, indicating that it may play an important role in the mulberry response to drought stress.

Conclusions

Our research shows that mulberry can activate proline and ABA biosynthesis pathways and produce a large amount of proline and ABA, which improves the drought resistance of mulberry.MaWRKYIII8was up-regulated and induced by drought and exogenous ABA, indicating thatMaWRKYIII8may be involved in the mulberry response to drought stress. These studies will help us to analyse the molecular mechanism underlying mulberry drought tolerance and provide important gene information and a theoretical basis for improving mulberry drought tolerance through molecular breeding in the future.
Safe birth in cultural safety in southern Mexico: a pragmatic non-inferiority cluster-randomised controlled trial
Authors: Sarmiento Iván , Paredes-Solís Sergio , de Jesús García Abraham , Maciel Paulino Nadia , Serrano de los Santos Felipe René , Legorreta-Soberanis José , Zuluaga Germán , Cockcroft Anne , Andersson Neil
Published: January 2022

Background

Available research on the contribution of traditional midwifery to safe motherhood focuses on retraining and redefining traditional midwives, assuming cultural prominence of Western ways. Our objective was to test if supporting traditional midwives on their own terms increases cultural safety (respect of Indigenous traditions) without worsening maternal health outcomes.

Methods

Pragmatic parallel-group cluster-randomised controlled non-inferiority trial in four municipalities in Guerrero State, southern Mexico, withNahua,Na savi,Me’phaaandNancue ñomndaaIndigenous groups. The study included all pregnant women in 80 communities and 30 traditional midwives in 40 intervention communities. Between July 2015 and April 2017, traditional midwives and their apprentices received a monthly stipend and support from a trained intercultural broker, and local official health personnel attended a workshop for improving attitudes towards traditional midwifery. Forty communities in two control municipalities continued with usual health services. Trained Indigenous female interviewers administered a baseline and follow-up household survey, interviewing all women who reported pregnancy or childbirth in all involved municipalities since January 2016. Primary outcomes included childbirth and neonatal complications, perinatal deaths, and postnatal complications, and secondary outcomes were traditional childbirth (at home, in vertical position, with traditional midwife and family), access and experience in Western healthcare, food intake, reduction of heavy work, and cost of health care.

Results

Among 872 completed pregnancies, women in intervention communities had lower rates of primary outcomes (perinatal deaths or childbirth or neonatal complications) (RD -0.06 95%CI − 0.09 to − 0.02) and reported more traditional childbirths (RD 0.10 95%CI 0.02 to 0.18). Among institutional childbirths, women from intervention communities reported more traditional management of placenta (RD 0.34 95%CI 0.21 to 0.48) but also more non-traditional cold-water baths (RD 0.10 95%CI 0.02 to 0.19). Among home-based childbirths, women from intervention communities had fewer postpartum complications (RD -0.12 95%CI − 0.27 to 0.01).

Conclusions

Supporting traditional midwifery increased culturally safe childbirth without worsening health outcomes. The fixed population size restricted our confidence for inference of non-inferiority for mortality outcomes. Traditional midwifery could contribute to safer birth among Indigenous communities if, instead of attempting to replace traditional practices, health authorities promoted intercultural dialogue.

Trial registration

Retrospectively registeredISRCTN12397283. Trial status: concluded.
Laparoscopic versus open reduction of idiopathic intussusception in children: an updated institutional experience
Authors: Zhao Jian , Sun Jun , Li Deyu , Xu Wei Jue
Published: January 2022

Background

In the reduction of intussusception, due to the lack of randomized, controlled, and prospective clinical trials to confirm the superiority of the laparoscopic approach over open surgery, more evidence was needed. This study aimed to compare the results of laparoscopy and open reduction of idiopathic intussusception in children as well as to illustrate some skills for the reduction of intussusception laparoscopically.

Methods

A retrospective review was performed to evaluate outcomes for patients with idiopathic intussusception who were treated laparoscopically (LAP group) from January 2015 to December 2019 and to compare the outcomes with laparotomy (OPEN group) during the same period.

Results

During the period studied, there were 162 patients treated surgically for intussusception: 62 LAP and 100 OPEN. No statistical differences were found in demographic data, clinical symptoms and signs, duration of symptoms, location and types of intussusception between the two groups. Conversion to open procedure was required for 11 patients in the LAP group. The operation time and time to oral intake were shorter in the LAP group while the difference was not significant. If the 11 conversion cases were excluded, the operation time and time to oral intake were significantly shorter (P < 0.05) in the LAP group. The length of stay was significantly shorter in the LAP group (P < 0.05). Intraoperative and postoperative complication rates between the two groups were comparable (P = 1.0).

Conclusion

Laparoscopy was safe and effective in the treatment of pediatric idiopathic intussusceptions. Pediatric surgeons with sophisticated minimally invasive skills should choose laparoscopy as the first choice in the treatment of idiopathic intussusceptions.
Psychosocial impacts of home-schooling on parents and caregivers during the COVID-19 pandemic
Authors: Calear Alison L. , McCallum Sonia , Morse Alyssa R. , Banfield Michelle , Gulliver Amelia , Cherbuin Nicolas , Farrer Louise M. , Murray Kristen , Rodney Harris Rachael M. , Batterham Philip J.
Published: January 2022

Background

The COVID-19 pandemic has been highly disruptive, with the closure of schools causing sudden shifts for students, educators and parents/caregivers to remote learning from home (home-schooling). Limited research has focused on home-schooling during the COVID-19 pandemic, with most research to date being descriptive in nature. The aim of the current study was to comprehensively quantify the psychosocial impacts of home-schooling on parents and other caregivers, and identify factors associated with better outcomes.

Methods

A nationally representative sample of 1,296 Australian adults was recruited at the beginning of Australian COVID-19 restrictions in late-March 2020, and followed up every two weeks. Data for the current study were drawn from waves two and three. Surveys assessed psychosocial outcomes of psychological distress, work and social impairment, and wellbeing, as well as a range of home-schooling factors.

Results

Parents and caregivers who were home-schooling during the COVID-19 pandemic experienced significantly higher levels of psychological distress and work/social impairment compared to those who were not home-schooling or had no school-aged children. A current mental health diagnosis or lower levels of perceived support from their child’s school negatively affected levels of psychological distress, work and social impairment, and wellbeing in parents and caregivers involved in home-schooling.

Conclusions

The mental health impacts of home-schooling were high and may rise as periods of home-schooling increase in frequency and duration. Recognising and acknowledging the challenges of home-schooling is important, and should be included in psychosocial assessments of wellbeing during periods of school closure. Emotional and instrumental support is needed for those involved in home-schooling, as perceived levels of support is associated with improved outcomes. Proactive planning by schools to support parents may promote better outcomes and improved home-schooling experiences for students.
Recent UK retirees’ views about the work-related factors which influenced their decision to retire: a qualitative study within the Health and Employment After Fifty (HEAF) cohort
Authors: Stevens Martin J. , Barker Mary , Dennison Elaine , Harris E. Clare , Linaker Cathy , Weller Susie , Walker-Bone Karen
Published: January 2022

Background

Lower birth rates and increasing longevity have resulted in ageing populations in European countries. These demographic changes place challenges on pension provision as numbers of those who are economically inactive and retired increase relative to those in paid work. Therefore, governments need workers to postpone retirement and work to older ages. Whilst health and wealth are important in retirement decision-making, considerably less is known about the effects of workplace factors. The aim of this study was to explore the views of recent UK retirees about the role that work-related factors played in their decision to retire.

Methods

This qualitative study was nested within the Health and Employment After Fifty (HEAF) cohort. People who had retired 3-6 years previously (not for health reasons) were purposively sampled to obtain the views of men and women from a range of socio-economic backgrounds and jobs. Semi-structured interviews were carried out by telephone using a pre-defined topic guide. Interviews were audio-recorded, transcribed and analysed thematically.

Results

Seventeen interviews were conducted. Thematic analysis showed that retirement decisions were complex and multi-factorial but that work-related factors contributed to decision-making in two main ways. First, some work factors pushed participants towards retirement. These were perceptions that: workplace change had affected the way they were valued or increased pressure on them; work demands, including commuting, had intruded excessively on personal time, effects that were exacerbated by modern technology; work was draining, isolating or under-appreciated; and /or that work was causing physical strain or discomfort relative to their perception of their capacity. In contrast, work factors could also cause participants to pull back towards work, particularly: autonomy; supportive work colleagues; a sense of being appreciated; and perceived job flexibility.

Conclusions

Recent retirees explained that their decision to retire was multi-factorial but work-related factors contributed importantly. Potentially, employers could: review workers’ perceptions about their work; their capacity in relation to job demands; increase flexibility; and facilitate a supportive work community to encourage longer working lives.
Preoperative predictors of health-related quality of life changes (EQ-5D and EQ VAS) after total hip and knee replacement: a systematic review
Authors: Schatz Caroline , Klein Nina , Marx Antonia , Buschner Peter
Published: January 2022

Background

Patient-reported outcomes are of ever-increasing importance in medical decision-making. The EQ-5D is one of the generic instruments measuring health-related quality of life (HRQoL) in arthroplasty. This review aimed to identify possible predictors of HRQoL changes for patients undergoing total knee replacements (TKR) or total hip replacements (THR).

Methods

A systematic literature review according to the PRISMA guidelines was conducted, searching several databases. Preoperative to postoperative HRQoL changes were evaluated in patients undergoing THR or TKR, using the EQ-5D visual analog scale (VAS) or the preference-based EQ-5D Index were evaluated. Articles were considered with prospectively or retrospectively collected data, as well as registry data, each with statistical analyses of patient-related factors.

Results

Eight hundred eighty-two articles were found, of which 21 studies met the inclusion criteria. Predictors were distinguished in alterable and non-alterable ones. The EQ-5D Index indicated a tendency towards beneficial improvements for patients with a high body mass index (BMI) (> 40) and no significant results for the VAS. Additionally, one study found that patient education and preoperative physiotherapy appeared to enhance HRQoL. Some evidence indicated that male gender was negatively associated with changes in the VAS and the EQ-5D Index, but one study reported the opposite. Changes in VAS and EQ-5D Index were lower for older patients, whereas a higher educational level seemed to be advantageous. A high Charnley class led to deteriorating changes in VAS, although a high Kellgren Lawrence classification was positively associated with the EQ-5D Index, in a limited number of studies. For all results, clinical relevance was calculated differently and mainly reported as uncertain or small.

Conclusions

The literature on this topic was weak and offers only limited guidance. Results for alterable predictors, such as the BMI, indicated valuable improvements for highly obese patients. Further, high-quality research is required to support medical decision-making.

Level of evidence

Level IV, according to the OCEBM Levels of Evidence Working Group.
Decrease in incidence of proximal femur fractures in the elderly population during the Covid-19 pandemic: a case–control study
Authors: Oulianski Maria , Rosinsky Philip J. , Fuhrmann Ariel , Sokolov Ruslan , Arriola Roberto , Lubovsky Omri
Published: January 2022

Background

The World Health Organization classified Covid-19 as a pandemic during the first months of 2020 as lockdown measures were implemented globally to mitigate the increasing incidence of Covid-19-related morbidity and mortality. The purpose of this study was to evaluate the effect of national lockdown measures on proximal femur fracture epidemiology. Our hypothesis was that due to the prolonged period of stay-at-home orders, we would observe a decrease in the incidence of proximal femur fractures during the years 2020–21.

Methods

A retrospective case–control study of 2784 hip fractures admitted to the emergency department at one hospital between January 1, 2010, and March 31, 2021, was conducted. Cases were stratified weekly, and an analysis was conducted comparing cases occurring during government-imposed lockdown periods of 2020–21 to corresponding periods during 2010–2019. Furthermore, the trend of cases throughout the year of 2020 was observed.

Results

Of all proximal femur fracture cases included, 2522 occurred between 2010–2019 and 261 during the Covid-19 period. There was no significant difference in age (81.95 vs. 82.09; P = 0.78) or gender (P = 0.12). There was a total decrease of 21.64% in proximal femur fracture per week during the entirety of the Covid-19 pandemic period compared to the previous years (3.64 ± 1.99 vs. 4.76 ± 0.83; P = 0.001). During all three lockdown periods, there was a significant decrease in proximal femur fracture cases per week (3.55 ± 2.60 vs. 4.87 ± 0.95; P = 0.04), and the most pronounced decrease occurred during the third lockdown period (2.89 ± 1.96 vs. 5.23 ± 1.18; P = 0.01).

Conclusion

We observed a total decrease in the number of proximal femur fractures occurring during the Covid-19 era compared to previous years and specifically a decrease of cases occurring during the government-imposed lockdown periods. The decrease in cases was more pronounced during the second and third lockdown periods.
What is the relationship between the breech presentation and femoral trochlear dysplasia? An experimental study of the breech presentation model in neonatal rats
Authors: Li Weifeng , Wang Shengjie , Tang Shiyu , Dong Zhenyue , Wang Fei
Published: January 2022

Background

The relationship between breech presentation and trochlear dysplasia has been confirmed. However, the pathological process of breech-related trochlear dysplasia remains unclear. This study aimed to establish an animal model to simulate breech presentation and to analyze the pathological process of the femoral trochlea.

Materials and Methods

One hundred and twenty neonatal rats were randomly assigned into a control group and two experimental groups that were swaddled (using surgical tape) to keep the hip flexed and knees extended to simulate human breech presentation for the 5 days (short Swaddling) and the 10 days (prolonged Swaddling) of life. Gross and cross-sectional observation, histological staining measurement in two experimental time points (5 and 10 days after birth) were conducted to evaluate the morphological changes of the femoral trochlea.

Results

The incidence of trochlear dysplasia increased with the Swaddling time. Rats in the prolonged Swaddling group had the high prevalence of trochlea dysplasia (52 of 60), followed by short Swaddling group (42 of 60). Gross and cross-sectional observation showed a shallower trochlea groove in two experimental groups. Histologicalstaining measurement indicated that the trochlear sulcus angle and trochlear sulcus depth were significantly different between the experimental group and the control group since day 5 and day 10.

Conclusion

In this model, breech presentation had an adverse effect on neonatal knees and could induce trochlear dysplasia. In addition, this study also showed that the more time in breech presentation, the more incidence of trochlear dysplasia.
Exploring research capacity and culture of allied health professionals: a mixed methods evaluation
Authors: Cordrey Terry , King Elizabeth , Pilkington Emma , Gore Katie , Gustafson Owen
Published: January 2022

Background

Despite the myriad benefits of research to patients, professionals, and organisations, fewer than 0.1% of the Allied Health Professions workforce are employed in clinical academic roles. Identified barriers include a lack of role modelling, management support, funding, and availability of clinical academic roles. Research capacity building is critical to improving Allied Health Professional research capability. The aim of this evaluation was to explore the current research capacity and culture of Allied Health Professionals to inform future tailored research capacity building strategies at a local level.

Methods

A mixed methods evaluation of research capacity and culture was conducted within the Allied Health Professions department of a large National Health Service Foundation Trust using an online research capacity and culture questionnaire, followed by focus groups. Staff were recruited using a purposive method with the questionnaire and subsequent focus groups completed between July and September 2020. Data from the questionnaire was analysed using simple descriptive statistics and after inductive coding, focus group data was analysed thematically.

Results

93 out of 278 staff completed the questionnaire and 60 staff members attended seven focus groups. The research capacity and culture survey reported the department’s key strength as promoting clinical practice based on evidence (median=8, range=6-9). A key reported weakness of the department was insufficient resources to support staff research training (med=4, 3-6). Respondents considered themselves most skilled in finding relevant literature (med=6, 5-8) and least skilled at securing research funding (med=1, 1-2). Greater than half of the respondents (n=50) reported not currently being involved with research. Five themes were identified from the focus groups: empowerment; building research infrastructure; fostering research skills; access for all; and positive research culture.

Conclusions

Allied Health Professionals recognise the benefits of research at teams and departmental level, but marginally at an individual level. Local research capacity building strategies should aim to address the role, responsibilities and barriers to Allied Health Profession research development at an individual level. To ensure all staff can engage, research infrastructure and empowerment are essential.
Mitonuclear incompatibility as a hidden driver behind the genome ancestry of African admixed cattle
Authors: Kwon Taehyung , Kim Kwondo , Caetano-Anolles Kelsey , Sung Samsun , Cho Seoae , Jeong Choongwon , Hanotte Olivier , Kim Heebal
Published: January 2022

Background

Africa is an important watershed in the genetic history of domestic cattle, as two lineages of modern cattle,Bos taurusandB. indicus, form distinct admixed cattle populations. Despite the predominantB. indicusnuclear ancestry of African admixed cattle,B. indicusmitochondria have not been found on the continent. This discrepancy between the mitochondrial and nuclear genomes has been previously hypothesized to be driven by male-biased introgression of AsianB. indicusinto ancestral AfricanB. taurus. Given that this hypothesis mandates extreme demographic assumptions relying on random genetic drift, we propose a novel hypothesis of selection induced by mitonuclear incompatibility and assess these hypotheses with regard to the current genomic status of African admixed cattle.

Results

By analyzing 494 mitochondrial and 235 nuclear genome sequences, we first confirmed the genotype discrepancy between mitochondrial and nuclear genome in African admixed cattle: the absence ofB. indicusmitochondria and the predominantB. indicusautosomal ancestry. We applied approximate Bayesian computation (ABC) to assess the posterior probabilities of two selection hypotheses given this observation. The results of ABC indicated that the model assuming both male-biasedB. indicusintrogression and selection induced by mitonuclear incompatibility explains the current genomic discrepancy most accurately. Subsequently, we identified selection signatures at autosomal loci interacting with mitochondria that are responsible for integrity of the cellular respiration system. By contrast withB. indicus-enriched genome ancestry of African admixed cattle, local ancestries at these selection signatures were enriched withB. taurusalleles, concurring with the key expectation of selection induced by mitonuclear incompatibility.

Conclusions

Our findings support the current genome status of African admixed cattle as a potential outcome of male-biasedB. indicusintrogression, where mitonuclear incompatibility exerted selection pressure againstB. indicusmitochondria. This study provides a novel perspective on African cattle demography and supports the role of mitonuclear incompatibility in the hybridization of mammalian species.
Short structural variants as informative genetic markers for ALS disease risk and progression
Authors: Theunissen Frances , Flynn Loren L. , Anderton Ryan S. , Akkari P. Anthony
Published: January 2022

There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms and can explain, in part, the phenotypic variability in ALS patients. Here, we discuss SSVs recently characterized by our laboratory and how these discoveries integrate into the current literature on ALS, particularly in the context of application to future clinical trials. These markers may help to identify and differentiate patients for clinical trials that have a similar ALS disease mechanism(s), thereby reducing the impact of participant heterogeneity. As evidence accumulates for the genetic markers discovered in SQSTM1, SCAF4, and STMN2, we hope to improve the outcomes of future ALS clinical trials.
Percutaneous ruminostomy guided by rumenoscopy: study in an experimental model in bovine fetus
Authors: dos Santos Gabriela Melo Alves , Borges Luisa Pucci Bueno , de Morais Hanna Lyce Magno , da Conceição Guilherme Barbara , dos Santos Albuquerque Rodrigo , Rossy Kayan Cunha , Gurgel Heytor Jales , do Espirito Santo Fernandes Camila , Barroso João Pedro Monteiro , do Santos Ribas Priscila , de Oliveira Monteiro Francisco Décio , Ferreira Chayanne Silva , Teixeira Pedro Paulo Maia
Published: January 2022

Background

Endosurgery is a surgical subspecialty that has been widely used in production animals, because it enables good visualization of abdominal organs and the diagnosis and treatment of several conditions in a minimally invasive manner, while preserving the animal’s well-being and causing a lower impact on animal production. Rumenostomy is one of the most common surgical procedures in ruminants. This procedure is used to allow access to the rumen for various purposes, especially nutritional and therapeutic studies, and it can be performed either in a conventional way or in a minimally invasive video-assisted manner. Another possibility of access to ruminants is through the rumenoscopy technique. The objective of this study is to describe a minimally invasive technique for rumenostomy using an endoscope, working on a bovine fetal corpse as an experimental model.

Results

The execution of the endoscopy-guided rumenostomy technique was simple and did not present major difficulties. The endoscope, its lighting and air pump, and the decubitus used provided a good anatomical visualization of the rumen, and it was possible to evaluate several regions of the organ. The mean duration of the procedure was 11.15 min.

Conclusions

The endoscopic rumenostomy technique using anatomical pieces of calves was shown to be feasible. It was performed in a simple and efficient way, particularly regarding the premise of preserving the animal’s well-being, due to its minimally invasive nature.
A comparative, observational study evaluating dosing characteristics and ovarian response using the recombinant human follicle-stimulating hormone pen injector with small-dose dial in assisted reproductive technologies treatment in Asia: IMPROVE study
Authors: Choi Bum Chae , Zhou Canquan , Ye Hong , Sun Yun , Zhong Ying , Gong Fei , Sini Ivan , Abramova Nadezda , Longobardi Salvatore , Hickey Miranda , D’Hooghe Thomas
Published: January 2022

Background

Ovarian stimulation during medically assisted reproduction treatment should be individualized to optimize outcomes and reduce complications. This study assessed whether use of the recombinant human follicle-stimulating hormone (r-hFSH) pen injector allowing small 12.5 IU dose increments resulted in lower r-hFSH dose per oocyte retrieved in a subgroup of patients at risk of OHSS, compared with r-hFSH injection devices allowing only 37.5 IU increments.

Methods

This multicenter, comparative, observational study evaluated patients from a prospective (study group) and historical (control group) cohort. The study group enrolled 1783 patients using the redesigned r-hFSH pen injector (GONAL-f®, Merck Healthcare KGaA, Darmstadt, Germany) from a prospective phase IV, non-interventional, open-label study, conducted in Korea, Vietnam, Indonesia, and China. The control group consisted of 1419 patients from a historical study using r-hFSH devices allowing 37.5 IU increments. In the study group, 397 patients were considered at risk of OHSS; this information was unavailable for the control group, so biomarkers and patient characteristics were used to match 123 patients from the study group and control group. Each center adhered to standard practice; starting dose and intra-cycle dose adjustments were allowed at any point. The primary endpoint, amount of r-hFSH (IU) administered per oocyte retrieved, was assessed in matched patients only. Additional outcomes and safety were assessed in the overall populations.

Results

Baseline characteristics were comparable between groups. Mean (SD) total dose of r-hFSH administered per oocyte retrieved in patients at risk of OHSS, was significantly lower in the study group compared with the control group (132.5 [85.2] vs. 332.7 [371.6] IU, P < 0.0001, n = 123). Implantation rate, clinical pregnancy rate, and live birth rates in the overall study and control groups were 30.0 vs. 20.6%, 50.3 vs. 40.7%, and 43.8 vs. 34.0%, respectively. OHSS incidence was significantly lower in the study group compared with the control group (27/1783 [1.5%] vs. 57/1419 [4.0%] patients, P < 0.0001). AEs were reported by 5.0% of patients in the study group.

Conclusions

A significantly lower r-hFSH dose per oocyte retrieved and lower OHSS incidence were observed in patients using the redesigned injector compared with patients using other injection devices.
Radiotherapy-induced toxicity in prostate cancer patients with hip prostheses
Authors: Fischer Andrea M. , Hoskin Peter J.
Published: January 2022

Introduction

Acute and late toxicity was analysed for prostate cancer patients with bilateral hip prostheses, who received fixed field intensity modulated radiotherapy (IMRT). The aims were (1) to establish whether toxicity rates differed from those of a control group with normal hips, (2) to develop a volumetric modulated arc therapy (VMAT) approach for patients with prostheses and (3) to compare doses to bladder and rectum for the control group, prostheses group and VMAT replans for the prostheses group.

Methods

Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using Common Terminology Criteria for Adverse Events version 5.0. The incidence of grade 2 or worse (G2+) toxicity was compared using Fisher’s exact test. Dose volume histograms (DVHs) and mean doses to organs at risk (OARs) were compared using signed rank tests.

Results

There were 17 patients in the prostheses group and 50 in the control group. Acute and late GU toxicity was similar. G2+ late GI toxicity incidence was 31% for the prostheses group and 14% for the control group (p = 0.14). Significant differences (p < 0.05) were seen between the OAR DVHs of the prostheses group who had IMRT and the control group for a range of intermediate doses. The rectum mean dose was significantly different (p < 0.001), but no difference was seen for the bladder mean dose (p = 0.08).

Conclusions

No significant differences were seen in GU and GI toxicity incidence between patients with bilateral hip prostheses and a control group. The DVHs for bladder and rectum were significantly higher for patients with prostheses planned with IMRT. Replanning using a VMAT technique significantly reduced doses to the OARs, whilst maintaining good planning target volume coverage.
Comparison of blood tonic efficacy and chemical constituents of Kadsura interior A.C. Smith and its closely related species
Authors: Xu Jing , Liu Jiushi , Li Bin , Wei Xueping , Qi Yaodong , Zhang Bengang , Liu Haitao , Xiao Peigen
Published: January 2022

Background

The stems of Kadsura interior A. C. Smith are used as traditional Chinese medicine (TCM) Kadsurae Caulis, with the traditional efficacy of tonifying and invigorating the blood, therefore being favored to treat blood deficiency (BD) widely. However, the stems of K. interior and its closely related species are morphologically similar and they may readily be misused as Kadsurae Caulis, thus likely to exert negative effects on clinical efficacy and clinical medication safety.

Methods

Firstly, blood tonic efficacies of the stems of K. interior (KIS) and its closely related species were compared using BD mouse model induced by 1-acetyl-2-phenylhydrazine (APH) and cyclophosphamide (CTX). Secondly, the chemical constituents from the stems of K. interior and its closely related species were evaluated and compared using a plant metabolomics approach. Plant metabolomics in this study aims at discovering differential metabolites and comprehensively assessing the chemical constituents by combining state-of-the-art high-resolution UPLC-Q/TOF–MS/MS technique and multivariate data analysis. Finally, based on the pharmacological data and the chemical constituents in UPLC-Q/TOF–MS fingerprints, the potential blood tonic active markers were screened by the spectrum-effect relationship analysis and quantified by UPLC-UV-DAD.

Results

The ethanol extract of the stems of K. interior significantly increased the levels of hematocrit (HCT), hemoglobin (HGB), and red blood cells (RBC) in BD mice. In addition, it significantly increased the serum levels of interleukin 3 (IL-3), granulocyte–macrophage colony-stimulating factor (GM-CSF), and macrophage-stimulating factor (M-CSF) in BD mice (P < 0.01). The blood tonic efficacy of the stems of K. interior was superior to those of its closely related species, especially at the dose of 200 mg/kg. Six differential compounds in the stems of K. interior were screened out to distinguish it from its closely related species. In combination with the results of the spectrum-effect relationship analysis, heteroclitin D, interiorin C, and heteroclitin G were identified as potential bioactive markers. The contents of heteroclitin D and heteroclitin G in the freeze-dried powder of KIS were 15.90 and 3.74 μg/mg.

Conclusions

This study illustrated the differences in the blood tonic efficacies and the chemical constituents of the stems of K. interior and its closely related species, and pinpointed the potential bioactive markers of K. interior.
Metabolic synthetic lethality by targeting NOP56 and mTOR in KRAS-mutant lung cancer
Authors: Yang Zhang , Liang Shun-Qing , Zhao Liang , Yang Haitang , Marti Thomas M. , Hegedüs Balazs , Gao Yanyun , Zheng Bin , Chen Chun , Wang Wenxiang , Dorn Patrick , Kocher Gregor J. , Schmid Ralph A. , Peng Ren-Wang
Published: January 2022

Background

Oncogenic KRAS mutations are prevalent in human cancers, but effective treatment of KRAS-mutant malignancies remains a major challenge in the clinic. Increasing evidence suggests that aberrant metabolism plays a central role in KRAS-driven oncogenic transformation. The aim of this study is to identify selective metabolic dependency induced by mutant KRAS and to exploit it for the treatment of the disease.

Method

We performed an integrated analysis of RNAi- and CRISPR-based functional genomic datasets (n = 5) to identify novel genes selectively required for KRAS-mutant cancer. We further screened a customized library of chemical inhibitors for candidates that are synthetic lethal with NOP56 depletion. Functional studies were carried out by genetic knockdown using siRNAs and shRNAs, knockout using CRISPR/Cas9, and/or pharmacological inhibition, followed by cell viability and apoptotic assays. Protein expression was determined by Western blot. Metabolic ROS was measured by flow cytometry-based quantification.

Results

We demonstrated that nucleolar protein 5A (NOP56), a core component of small nucleolar ribonucleoprotein complexes (snoRNPs) with an essential role in ribosome biogenesis, confers a metabolic dependency by regulating ROS homeostasis in KRAS-mutant lung cancer cells and that NOP56 depletion causes synthetic lethal susceptibility to inhibition of mTOR. Mechanistically, cancer cells with reduced NOP56 are subjected to higher levels of ROS and rely on mTOR signaling to balance oxidative stress and survive. We also discovered that IRE1α-mediated unfolded protein response (UPR) regulates this process by activating mTOR through p38 MAPK. Consequently, co-targeting of NOP56 and mTOR profoundly enhances KRAS-mutant tumor cell death in vitro and in vivo.

Conclusions

Our findings reveal a previously unrecognized mechanism in which NOP56 and mTOR cooperate to play a homeostatic role in the response to oxidative stress and suggest a new rationale for the treatment of KRAS-mutant cancers.
The SF3B1R625H mutation promotes prolactinoma tumor progression through aberrant splicing of DLG1
Authors: Guo Jing , Li Chuzhong , Fang Qiuyue , Liu Yulou , Wang Dawei , Chen Yiyuan , Xie Weiyan , Zhang Yazhuo
Published: January 2022

Background

Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1R625H), but its functional effects and underlying molecular mechanisms remain largely unexplored.

Methods

Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA.

Results

Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1R625H allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1R625H promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1R625H and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway.

Conclusions

Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1R625H mutation.
Effects of the addition of transcutaneous electrical stimulation to non-pharmacological measures in labor pain: study protocol for a randomized controlled trial
Authors: Dias Naiara Toledo , Santos Patrícia Roberta , Cândido Thais Alves , Pinto Rogério de Melo Costa , Resende Ana Paula Magalhães , Pereira-Baldon Vanessa Santos
Published: January 2022

Background

Labor, although natural and physiological, is a period that can be marked by stress, pain, anxiety, suffering, fear, and anguish for a woman. Thus, non-pharmacological methods that reduce pain during labor are important to allow a better experience without the use of medications. Therefore, the aim of this study is to evaluate the effects of non-pharmacological pain relief methods, added or not to the application of transcutaneous electrical stimulation (TENS), on pain, satisfaction with the childbirth, duration of labor, and newborn conditions.

Methods

This is a randomized controlled clinical trial, with a non-probabilistic convenience sample, composed of women in the first active stage of labor, admitted to a public institution. The parturients will be divided into 3 groups: group 1 (n = 36) composed of parturients who will have continuous support and will be encouraged to walk, adopting different positions with the use of the Swiss ball and receiving back massage for 30 min; group 2 (n = 36) composed of parturients who will also have continuous support and will be encouraged to walk, adopt different positions using the Swiss ball, and will receive the application of TENS for 30 min; and group 3 (n = 36) composed of parturients who will have continuous support and will be encouraged to walk, adopting different positions with the use of the Swiss ball, and will receive placebo TENS application for 30 min. The outcomes evaluated in the study will be pain intensity assessed by the visual analog scale of pain applied before, immediately after, and 30 min and 1 h after the interventions; Experience and Satisfaction with Childbirth Questionnaire (QESP) applied 12 to 24 h after delivery; and data regarding delivery (type of delivery, total duration of labor, and possible obstetric complications) and neonate (weight, height, possible complications, Apgar score in the first and fifth minutes).

Discussion

With this research, it is expected to understand the effects of the intervention through TENS electrostimulation added to other non-pharmacological methods for pain management during labor.

Trial registration

Brazilian Registry of Clinical Trials (REBEC) RBR-68kh6j. Registered on March 17, 2020
Effectiveness of a high-intensive trauma-focused, family-based therapy for youth exposed to family violence: study protocol for a randomized controlled trial
Authors: Fictorie Valerie , Jonkman Caroline , Visser Margreet , Vandenbosch Marjolein , Steketee Majone , Schuengel Carlo
Published: January 2022

Background

Family violence is a common problem with direct adverse effects on children as well as indirect effects through disruption of parenting and parent-child relationships. The complex interrelationships between family violence, parenting, and relationships make recovery from psychological responses difficult. In more than half of the families referred to mental health care after family violence, the violence continues. Also, the effect sizes of “golden standard” treatments are generally lower for complex trauma compared to other forms of trauma. In the treatment of complex trauma, trauma-focused therapies including cognitive restructuring and imaginal exposure are most effective, and intensifying therapy results in faster symptom reduction. Furthermore, there is promising evidence that adding a parental component to individual trauma treatment increases treatment success. In family-based intensive trauma treatment (FITT), these factors are addressed on an individual and family level in a short period of time to establish long-term effects on the reduction of trauma symptoms and recovery of security in the family. This randomized controlled multicentre study tests if FITT is an effective treatment for concurrent reduction of trauma symptoms of children, improvement of parenting functioning, and increasing emotional and physical security in children, through the improvement of parent-child relationships.

Methods

The effectiveness of FITT will be tested by a RCT design. A total of 120 adolescents with a history of family violence and PTS symptoms will be randomized to (a) an intensive trauma treatment with a parent and systemic component (FITT), (b) an intensive trauma treatment without these components (ITT), and (c) treatment as usual (TAU, low-frequency trauma treatment with parent therapy and family sessions). Changes in children’s trauma symptoms, child and parent functioning, and emotional and physical security in the family will be monitored before, during, after, and at 3 months follow-up.

Discussion

Comparing these interventions with and without a high intensive frequency and parenting and family components can help to understand if and how these interventions work and can contribute to the ambition to recover from the impact of family violence and restore emotional and physical security for children and young people.

Trial registration

Netherlands Trial Register Trial NL8592. Registered on 4 May 2020