bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodontal effect of augmented corticotomy-assisted orthodontics versus conventional orthodontics in treatment of adult patients with bialveolar protrusion
Authors: Wang Bing , Xi WenQiong , Chen Hui , Shao Jinlong , Song Aimei , Zhang Fan
Published: March 2022

Background

The patients of bialveolar protrusion always demonstrate thin anterior alveoli which may aggravate subsequent gingival recession and bone loss during retraction. This study aimed to investigate the periodontal changes, including alveolar height, thickness, and area, and the width of keratinized gingiva, in mandibular anterior teeth after augmented corticotomy-assisted orthodontics (ACAO) compared with traditional orthodontics.

Methods

Twenty adult patients with skeletal class I bialveolar protrusion were selected from two groups: ACAO group (augmented corticotomy on the labial side of the anterior mandibular teeth, n = 10) and control group (conventional orthodontics, n = 10). In all patients, four first premolars were extracted and the incisors were retracted under the maximum anchorage. The measurements included the labial alveolar bone area, vertical alveolar bone height, alveolar bone thickness surrounding the mandibular anterior teeth, root length, gingival recession and width of keratinized gingiva after alignment (T0) and 3 months after space closure (T1).

Results

The labial alveolar height, area, and thicknesses all decreased after space closure in the control group but significantly increased in the ACAO group. The decrease in the lingual alveolar height was statistically less in the ACAO group than that in the control group. Besides, the width of keratinized gingiva increased in the ACAO group but decreased in the control group. There was no significant difference in the changes of root length between groups. The dentoalveolar changes between anterior teeth were consistent but with different scales. The lateral incisors gained the most labial bone height and area.

Conclusion

Compared to conventional orthodontics, ACAO provided a more favorable effect of improving periodontal status surrounding the mandibular anterior teeth for Class I maxillary protrusion patients.
Assessment of chemical, ultrasonic, diode laser, and Er:YAG laser application on debonding of ceramic brackets
Authors: Khalil Ahmed S. , Tamish Nazla M. , Elkalza Ahmed R.
Published: March 2022

Background

Risk of enamel damage that often accompanies ceramic brackets debonding raises the demand of finding an optimal method for debonding of them without adverse effects. Different techniques were proposed in an attempt to facilitate their debonding. Comparison of these techniques is crucial. The aim of this study was to evaluate and compare different techniques for debonding of ceramic brackets in terms of shear bond strength and adhesive remnant index.

Materials and methods

A total of 100 extracted premolars were randomly allocated into 5 groups. Ceramic brackets were then bonded to teeth using light cure composite resin. Among test groups; group I: served as control, group II: chemical aided debonding via peppermint oil, group III: ultrasonic aided debonding, group IV: diode laser aided debonding, and group V: Er:YAG laser aided debonding. Brackets were shear tested using universal testing machine followed by ARI assessment and evaluation of enamel microstructure was performed using scanning electron microscopy.

Results

A significantly lower shear bond strength was found in ultrasonic, diode, and Er:YAG laser groups. However, no significant difference was found in the chemical group. A significantly higher adhesive remnant index was found solely in Er:YAG laser group with minimal enamel microstructure alterations.

Conclusions

Er:YAG laser is a promising tool in debonding ceramic brackets. Ultrasonic and diode laser significantly reduced shear bond strength. Yet, adhesive remnant index in both groups revealed no difference. Chemical aided debonding had little effect and hence, it cannot be recommended without further development.
Prevalence of dysmenorrhea among reproductive age group in Saudi Women
Authors: Bakhsh Hanadi , Algenaimi Eatedal , Aldhuwayhi Raghad , AboWadaan Maha
Published: March 2022

Background

The condition of recurrent, crampy, lower abdominal pain during menses is defined as dysmenorrhea. The study aims to assess the factors affecting the prevalence of primary and secondary dysmenorrhea among Saudi women from the reproductive age group.

Methods

A cross-sectional survey-based study recruited 1199 participants through a systematic random sampling technique. The study was carried out among the reproductive age group in Saudi women (total number of 1199) who are more than 18-year-old and less than 45-year-old in Riyadh, King Dom of Saudi Arabia, using an electronic questionnaire.

Results

The observed dysmenorrhea in the study; 1107 (92.3%) women had non-pathological dysmenorrhea (primary) while 92 (7.7%) women had pathological dysmenorrhea (secondary) respectively.

Conclusion

In the present study, the prevalence of dysmenorrhea was high among the recruited Saudi women. The study suggests the inclusion of health education programs for students at the school and university level to deal with problems associated with dysmenorrhea that limit their interference with the student’s life.
Antimicrobial activity of Bacillus sp. isolated strains of wild honey
Authors: Hallaj-Nezhadi Somayeh , Hamdipour Rasoul , Shahrvirani Mohamad , Zare tin Roya , Chapeland-leclerc Florence , Ruprich-Robert Gwenael , Esnaashari Solmaz , Elyasi Far Babak , Dilmaghani Azita
Published: March 2022

Background

Multi-drug resistant bacteria hazards to the health of humans could be an agent in the destruction of human generation. Natural products of Bacillus species are the main source to access progressive antibiotics that can be a good candidate for the discovery of novel antibiotics. Wild honey as a valuable food has been used in medicine with antimicrobial effects.

Objective

Bacillus strains isolated from wild honey were evaluated for the potential antimicrobial activity against human and plant bacterial and fungal pathogens.

Methods

Three bacterial isolates were identified as strain Khuz-1 (98.27% similarity with Bacillus safensis subsp. Safensis strain FO-36bT), strain Khuz-2 (99.18% similarity with Bacillus rugosus strain SPB7T), and strain Khuz-3 (99.78% similarity with Bacillus velezensis strain CR-502 T) by 16S rRNA gene sequences. The strains were characterized by their ability to inhibit the growth of human and phytopathogenic fungi.

Results

The results indicated that B. rugosus strain Khuz-2 inhibited the growth of phytopathogenic and human fungal more effective than other ones. It seems that the strain Khuz-2 has a suitable antimicrobial and antifungal potential as a good candidate for further pharmaceutical research.

Conclusion

Based on the results of GC–MS, Pyrrolo [1,2-a] pyrazine-1,4-dion, hexahydro-3-(2-methylpropyle) (PPDHM) was the major compound for all strains which have a various pharmacological effect. Isolation and identification of beneficial bacteria from natural sources can play an important role in future pharmaceutical and industrial applications.
When medical trainees encountering a performance difficulty: evidence from pupillary responses
Authors: Liu Xin , Sanchez Perdomo Yerly Paola , Zheng Bin , Duan Xiaoqin , Zhang Zhongshi , Zhang Dezheng
Published: March 2022

Background

Medical trainees are required to learn many procedures following instructions to improve their skills. This study aims to investigate the pupillary response of trainees when they encounter moment of performance difficulty (MPD) during skill learning. Detecting the moment of performance difficulty is essential for educators to assist trainees when they need it.

Methods

Eye motions were recorded while trainees practiced the thoracostomy procedure in the simulation model. To make pupillary data comparable among trainees, we proposed the adjusted pupil size (APS) normalizing pupil dilation for each trainee in their entire procedure. APS variables including APS, maxAPS, minAPS, meanAPS, medianAPS, and max interval indices were compared between easy and difficult subtasks; the APSs were compared among the three different performance situations, the moment of normal performance (MNP), MPD, and moment of seeking help (MSH).

Results

The mixed ANOVA revealed that the adjusted pupil size variables, such as the maxAPS, the minAPS, the meanAPS, and the medianAPS, had significant differences between performance situations. Compared to MPD and MNP, pupil size was reduced during MSH. Trainees displayed a smaller accumulative frequency of APS during difficult subtask when compared to easy subtasks.

Conclusions

Results from this project suggest that pupil responses can be a good behavioral indicator. This study is a part of our research aiming to create an artificial intelligent system for medical trainees with automatic detection of their performance difficulty and delivering instructional messages using augmented reality technology.
Ethics education to support ethical competence learning in healthcare: an integrative systematic review
Authors: Andersson Henrik , Svensson Anders , Frank Catharina , Rantala Andreas , Holmberg Mats , Bremer Anders
Published: March 2022

Background

Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethical values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions.

Methods

In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms ‘health personnel’, ‘students’, ‘ethics’, ‘moral’, ‘simulation’, and ‘teaching’. In total, 40 articles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis.

Results

The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient’s best interests, along with making decisions about what needs to be done in a specific situation.

Conclusions

The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals’ and students’ readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.
Predicting miRNA-disease associations via layer attention graph convolutional network model
Authors: Han Han , Zhu Rong , Liu Jin-Xing , Dai Ling-Yun
Published: March 2022

Background

MiRNA is a class of non-coding single-stranded RNA molecules with a length of approximately 22 nucleotides encoded by endogenous genes, which can regulate the expression of other genes. Therefore, it is very important to predict the associations between miRNA and disease. Predecessors developed a new prediction method of drug-disease association, and it achieved good results.

Methods

In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. First, we integrate three associations into a heterogeneous network, such as the known miRNA-disease association, miRNA-miRNA similarities and disease-disease similarities, next we apply graph convolution network to learn the embedding of miRNA and disease. We use an attention mechanism to combine embedding from multiple convolution layers. Unobserved miRNA-disease associations are scored based on integrated embedding.

Results

After fivefold cross-validations, the value of AUC is reached 0.9091, which is higher than other prediction methods and baseline methods.

Conclusions

In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. LAGCN has achieved good performance in predicting miRNA-disease associations, and it is superior to other association prediction methods and baseline methods.
Impact of a system to assist in clinical decision-making in primary healthcare in Catalonia: prescription Self Audit
Authors: Pons-Mesquida M. Àngels , Oms-Arias Míriam , Figueras Albert , Diogène-Fadini Eduard
Published: March 2022

Background

In 2008, in the context of a complete computerisation of medical records, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a system in its electronic clinical workstation (ECW) to assist decision-making at the prescription level. This system is known as Self Audit, and it supports physicians in reviewing the medication of their patients. Self Audit provides lists of patients presenting medication-related problems (MRPs) that have potential for improvement, and provides therapeutic recommendations that are easy to apply from the system itself. The aim of this study was to analyse the main results derived from the use of Self Audit in primary care (PC) in Catalonia, and the effect of an incentive-based safety indicator on the results obtained.

Methods

A descriptive cross-sectional study was carried out to analyse variations in the MRPs detected by Self Audit during 2016, 2017, and 2018 in PC in Catalonia. The effect of a safety indicator on the results obtained was also studied. This safety indicator includes the most clinically relevant MRPs (i.e., therapeutic duplications, safety alerts from the Spanish Medicines Agency, and incidences of polymedication in patients over 65 years of age). Variation in the MRPs was measured using the differences between two evaluation points (initial and final). An MRP was considered resolved if the recommendation specified in the alert was followed. The prescriptions of 6411 PC doctors of the ICS who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed.

Results

Analysis of the total safety-based MRPs detected by Self Audit gave overall resolutions from April to December of 9% (21,547) in 2016, 7% (15,924) in 2017, and 1% (2392) in 2018 out of the total number of MRPs recorded in April each year. Examination of the 3 types of MRPs with the highest clinical relevance that were linked to the safety indicator gave overall resolutions of 41% in 2016 (17,358), 20% in 2017 (7655), and 21% in 2018 (8135).

Conclusions

The ICS Self Audit tool assists in reducing the number of safety-based MRPs in a systematic manner, and yields superior results for the MRPs linked to a safety indicator included in the incentives of PC physicians.
Barriers to tuberculosis case finding in primary and secondary health facilities in Ghana: perceptions, experiences and practices of healthcare workers
Authors: Der Joyce B. , Grant Alison D. , Grint Daniel , Narh Clement T. , Bonsu Frank , Bond Virginia
Published: March 2022

Background

Ghana’s national tuberculosis (TB) prevalence survey conducted in 2013 showed higher than expected TB prevalence indicating that many people with TB were not being identified and treated. Responding to this, we assessed barriers to TB case finding from the perspective, experiences and practices of healthcare workers (HCWs) in rural and urban health facilities in the Volta region, Ghana.

Methods

We conducted structured clinic observations and in-depth interviews with 12 HCWs (including five trained in TB case detection) in four rural health facilities and a municipal hospital. Interview transcripts and clinic observation data were manually organised, triangulated and analysed into health system-related and HCW-related barriers.

Results

The key health system barriers identified included lack of TB diagnostic laboratories in rural health facilities and no standard referral system to the municipal hospital for further assessment and TB testing. In addition, missed opportunities for early diagnosis of TB were driven by suboptimal screening practices of HCWs whose application of the national standard operating procedures (SOP) for TB case detection was inconsistent. Further, infection prevention and control measures in health facilities were not implemented as recommended by the SOP. HCW-related barriers were mainly lack of training on case detection guidelines, fear of infection (exacerbated by lack of appropriate personal protective equipment [PPE]) and lack of motivation among HCWs for TB work. Solutions to these barriers suggested by HCWs included provision of at least one diagnostic facility in each sub-municipality, provision of transport subsidies to enable patients’ travel for testing, training of newly-recruited staff on case detection guidelines, and provision of appropriate PPE.

Conclusion

TB case finding was undermined by few diagnostic facilities; inconsistent referral mechanisms; poor implementation, training and quality control of a screening tool and guidelines; and HCWs fearing infection and not being motivated. We recommend training for and quality monitoring of TB diagnosis and treatment with a focus on patient-centred care, an effective sputum transport system, provision of the TB symptom screening tool and consistent referral pathways from peripheral health facilities.
The clinically led worforcE and activity redesign (CLEAR) programme: a novel data-driven healthcare improvement methodology
Authors: Corner Evelyn J. , Camilleri Matthew , Dholakia Shruti , Gredal Charlotte , Hansen Tina , Jeans John , LeNovere Marie , Mallender Jacqueline , Monkhouse Alex , Purkiss Claire , Ting Tai Ken , Vindrola-Padros Cecilia , Welfare Stephen , Wood Danny , Wood James ,   on behalf of the CLEAR Faculty
Published: March 2022

Background

The NHS is facing substantial pressures to recover from the COVID-19 pandemic. Optimising workforce modelling is a fundamental component of the recovery plan. The Clinically Lead workforcE and Activity Redesign (CLEAR) programme is a unique methodology that trains clinicians to redesign services, building intrinsic capacity and capability, optimising patient care and minimising the need for costly external consultancy. This paper describes the CLEAR methodology and the evaluation of previous CLEAR projects, including the return on investment.

Methods

CLEAR is a work-based learning programme that combines qualitative techniques with data analytics to build innovations and new models of care. It has four unique stages: (1) Clinical engagement- used to gather rich insights from stakeholders and clinicians. (2) Data interrogation- utilising clinical and workforce data for cohort analysis. (3) Innovation- using structured innovation methods to develop new models of care. (4) Recommendations- report writing, impact assessment and presentation of key findings to executive boards. A mixed-methods formative evaluation was carried out on completed projects, which included semi-structured interviews and surveys with CLEAR associates and stakeholders, and a health economic logic model that was developed to link the inputs, processes, outputs and the outcome of CLEAR as well as the potential impacts of the changes identified from the projects.

Results

CLEAR provides a more cost-effective delivery of complex change programmes than the alternatives – resulting in a cost saving of £1.90 for every £1 spent independent of implementation success. Results suggest that CLEAR recommendations are more likely to be implemented compared to other complex healthcare interventions because of the levels of clinical engagement and have a potential return on investment of up to £14 over 5 years for every £1 invested. CLEAR appears to have a positive impact on staff retention and wellbeing, the cost of a CLEAR project is covered if one medical consultant remains in post for a year.

Conclusions

The unique CLEAR methodology is a clinically effective and cost-effective complex healthcare innovation that optimises workforce and activity design, as well as improving staff retention. Embedding CLEAR methodology in the NHS could have substantial impact on patient care, staff well-being and service provision.
Toxoplasma gondii is not an important contributor to poor reproductive performance of primiparous ewes from southern Australia: a prospective cohort study
Authors: Clune Thomas , Lockwood Amy , Hancock Serina , Thompson Andrew N. , Bruce Mieghan , Beetson Sue , Campbell Angus J. , Glanville Elsa , Brookes Daniel , Trengove Colin , O’Handley Ryan , Jacobson Caroline
Published: March 2022

Background

Toxoplasma gondii causes reproductive losses in sheep worldwide, including Australia. The reproductive performance of primiparous ewes is typically lower than for mature, multiparous ewes, and younger ewes are more likely to be immunologically naïve and therefore more susceptible to reproductive disease if T. gondii infection occurs during pregnancy. The aim of this study was to assess the impact of infection with T. gondii on the reproductive performance of primiparous ewes in southern Australia using a prospective cohort study. This will inform the need for targeted control strategies for T. gondii in Australian sheep.

Results

Toxoplasma gondii seropositivity using indirect ELISA was detected at 16/28 farms located across southern Australia. Apparent seropositivity to T. gondii was lower in primiparous ewes (1.1, 95% confidence interval (CI) 0.6, 1.8) compared to mature, multiparous ewes (8.1, 95% CI 6.0, 10.5; P < 0.001). Toxoplasma gondii seroconversion during the gestation and lambing period was confirmed for 11/1097 (1.0, 95% CI 0.5, 1.7) of pregnant primiparous ewes that failed to raise a lamb, and 1/161 (0.6, 95% CI 0.1, 2.9) primiparous ewes with confirmed mid-pregnancy abortion.

Conclusions

Low frequency of detection of T. gondii seroconversion during gestation and low frequency of seropositivity to T. gondii suggests that toxoplasmosis was not an important contributor to reproductive losses in primiparous ewes on farms located over a wide geographical area in southern Australia.
Clinical and diagnostic characteristics of complex III mitopathy due to novel BCS1L gene mutation in a Saudi patient
Authors: Al Qurashi Mansour , Mustafa Ahmed , Aga Syed Sameer , Ahmad Abrar , El-Farra Abdellatif , Shawli Aiman , Al Hindi Mohammed , Hasosah Mohammed
Published: March 2022

Background

Of the many types of mitochondrial diseases, mutations affecting BCS1L gene are regarded as chief cause of the defective mitochondrial complex-III, affecting normal mitochondrial functioning, and leading to wide variety of phenotypes.

Case presentation

In this case report we describe a novel genotype linked to a unique phenotype in a Saudi patient born of a consanguineous marriage. Detailed genetic analysis and whole genome sequencing identified a novel homozygous missense mutation in exon 5 c.712A > G (p.Ser328Gly) of the BCS1L gene, with predicted deleterious effects on the functioning AAA+-ATPase domain of the protein characterized by distinct clinical presentation associated with profound multisystem involvement, conductive hearing loss, absent external auditory canal, low posterior hair line, short neck, micro and retrognathia, over riding fingers, rocker bottom foot, small phallus with bilateral absent testis (empty scrotum) and intolerable lactic acidosis.

Conclusions

A pathogenic effect of this novel BCS1L mutation was reflected in the patient with his failure to thrive and a complex clinical and metabolic phenotype.
Epidemiology, healthcare utilization, and related costs among patients with IPF: results from a German claims database analysis
Authors: Kreuter Michael , Picker Nils , Schwarzkopf Larissa , Baumann Severin , Cerani Agustin , Postema Roelien , Maywald Ulf , Dittmar Axel , Langley Jonathan , Patel Haridarshan
Published: March 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive form of fibrosing interstitial pneumonia with poor survival. This study provides insight into the epidemiology, cost, and disease course of IPF in Germany.

Methods

A cohort of incident patients with IPF (n = 1737) was identified from German claims data (2014–2019). Incidence and prevalence rates were calculated and adjusted for age differences compared with the overall German population. All-cause and IPF-related healthcare resource utilization as well as associated costs were evaluated per observed person-year (PY) following the initial IPF diagnosis. Finally, Kaplan–Meier analyses were performed to assess time from initial diagnosis to disease deterioration (using three proxy measures: non-elective hospitalization, IPF-related hospitalization, long-term oxygen therapy [LTOT]); antifibrotic therapy initiation; and all-cause death.

Results

The cumulative incidence of IPF was estimated at 10.7 per 100,000 individuals in 2016, 10.9 in 2017, 10.5 in 2018, and 9.6 in 2019. The point prevalence rates per 100,000 individuals for the respective years were 21.7, 23.5, 24.1, and 24.1. On average, ≥ 14 physician visits and nearly two hospitalizations per PY were observed after the initial IPF diagnosis. Of total all-cause direct costs (€15,721/PY), 55.7% (€8754/PY) were due to hospitalizations and 29.1% (€4572/PY) were due to medication. Medication accounted for 49.4% (€1470/PY) and hospitalizations for 34.8% (€1034/PY) of total IPF-related direct costs (€2973/PY). Within 2 years of the initial IPF diagnosis (23.6 months), 25% of patients died. Within 5 years of diagnosis, 53.1% of patients had initiated LTOT; only 11.6% were treated with antifibrotic agents. The median time from the initial diagnosis to the first non-elective hospitalization was 5.5 months.

Conclusion

The incidence and prevalence of IPF in Germany are at the higher end of the range reported in the literature. The main driver for all-cause cost was hospitalization. IPF-related costs were mainly driven by medication, with antifibrotic agents accounting for around one-third of the total medication costs even if not frequently prescribed. Most patients with IPF do not receive pharmacological treatment, highlighting the existing unmet medical need for effective and well-tolerated therapies.
Study on the mechanism of efficient extracellular expression of toxic streptomyces phospholipase D in Brevibacillus choshinensis under Mg2+ stress
Authors: Chen Shaofeng , Xiong Weide , Zhao Xurui , Luo Weiyi , Yan Xuhui , Lu Yinghua , Chen Cuixue , Ling Xueping
Published: March 2022

Background

Phospholipase D (PLD) has significant advantages in the food and medicine industries due to its unique transphosphatidylation. However, the high heterologous expression of PLD is limited by its cytotoxicity. The present study sought to develop an efficient and extracellular expression system of PLD in the non-pathogenic Brevibacillus choshinensis (B. choshinensis).

Results

The extracellular PLD was effectively expressed by the strong promoter (P2) under Mg2+ stress, with the highest activity of 10 U/mL. The inductively coupled plasma–mass spectrometry (ICP-MS) results elucidated that the over-expression of PLD by P2 promoter without Mg2+ stress induced the ionic homeostasis perturbation caused by the highly enhanced Ca2+ influx, leading to cell injury or death. Under Mg2+ stress, Ca2+ influx was significantly inhibited, and the strengths of P2 promoter and HWP gene expression were weakened. The study results revealed that the mechanism of Mg2+ induced cell growth protection and PLD expression might be related to the lowered strength of PLD expression by P2 promoter repression to meet with the secretion efficiency of B. choshinensis, and the redistribution of intracellular ions accompanied by decreased Ca2+ influx.

Conclusions

The PLD production was highly improved under Mg2+ stress. By ICP-MS and qPCR analysis combined with other results, the mechanism of the efficient extracellular PLD expression under Mg2+ stress was demonstrated. The relatively low-speed PLD expression during cell growth alleviated cell growth inhibition and profoundly improved PLD production. These results provided a potential approach for the large-scale production of extracellular PLD and novel insights into PLD function.
Factors associated with a malaria outbreak at Tongogara refugee camp in Chipinge District, Zimbabwe, 2021: a case–control study
Authors: Takarinda Kudzai Patience , Nyadundu Simon , Govha Emmanuel , Gombe Notion Tafara , Chadambuka Addmore , Juru Tsitsi , Tshimanga Mufuta
Published: March 2022

Background

Malaria is a leading cause of morbidity and mortality among forcibly displaced populations, including refugees, approximately two-thirds of whom reside in malaria endemic regions. Data from the rapid disease notification system (RDNS) reports for Manicaland Province in Zimbabwe showed that despite implementation of malaria control initiatives, there was an increase in number of malaria cases above action thresholds at Tongogara refugee camp in Chipinge district during weeks 12–14 of 2021. An investigation that described the outbreak by person, place and time was conducted. Malaria emergency preparedness, response, and appropriateness of case management were assessed. The factors associated with contracting malaria were determined to enable the formulation of appropriate interventions, establish control, and prevent future malaria outbreaks among this vulnerable population.

Methods

A 1:1 unmatched case–control study involving 80 cases and 80 controls was conducted using interviewer-administered questionnaires at household level. Data was entered into Epi Data version 3.1 and quantitative analysis was done using Epi Info™ version 7.2.2.6 to generate medians, proportions, odds ratios and their 95% confidence intervals.

Results

Malaria cases were distributed throughout the 10 residential sections within Tongogara refugee camp, the majority being from section 7, 28 (35%). Despite constituting 11% of the total population, Mozambican nationals accounted for 36 (45%) cases. Males constituted 47 (59%) among cases which was comparable to controls 43 (54%), p = 0.524. The median age for cases was 15 years [Interquartile range (IQR), 9–26] comparable to controls, which was 17 years (IQR, 10–30) (p = 0.755). Several natural and man-made potential vector breeding sites were observed around the camp. Risk factors associated with contracting malaria were engaging in outdoor activities at night [AOR = 2.74 (95% CI 1.04–7.22), wearing clothes that do not cover the whole body during outdoor activities [AOR 4.26 (95% CI, 1.43–12.68)], while residing in a refugee housing unit reduced the risk of contracting malaria [AOR = 0.18 (CI, 0.06–0.55)].

Conclusions

The malaria outbreak at Tongogara refugee camp reemphasizes the role of behavioural factors in malaria transmission. Intensified health education to address human behaviours that expose residents to malaria, habitat modification, and larviciding to eliminate mosquito breeding sites were recommended.
The ecdysone receptor regulates several key physiological factors in Anopheles funestus
Authors: Maharaj Surina , Ekoka Elodie , Erlank Erica , Nardini Luisa , Reader Janette , Birkholtz Lyn-Marie , Koekemoer Lizette L.
Published: March 2022

Background

Malaria is a devastating disease, transmitted by female Anopheles mosquitoes infected with Plasmodium parasites. Current insecticide-based strategies exist to control the spread of malaria by targeting vectors. However, the increase in insecticide resistance in vector populations hinder the efficacy of these methods. It is, therefore, essential to develop novel vector control methods that efficiently target transmission reducing factors such as vector density and competence. A possible vector control candidate gene, the ecdysone receptor, regulates longevity, reproduction, immunity and other physiological processes in several insects, including malaria vectors. Anopheles funestus is a prominent vector in sub-Saharan Africa, however, the function of the ecdysone receptor in this mosquito has not previously been studied. This study aimed to determine if the ecdysone receptor depletion impacts An. funestus longevity, reproduction and susceptibility to Plasmodium falciparum infection.

Methods

RNA interference was used to reduce ecdysone receptor expression levels in An. funestus females and investigate how the above-mentioned phenotypes are influenced. Additionally, the expression levels of the ecdysone receptor, and reproduction genes lipophorin and vitellogenin receptor as well as the immune gene, leucine rich immune molecule 9 were determined in ecdysone receptor-depleted mosquitoes using quantitative polymerase chain reaction.

Results

Ecdysone receptor-depleted mosquitoes had a shorter lifespan, impaired oogenesis, were less fertile, and had reduced P. falciparum infection intensity.

Conclusions

Overall, this study provides the first experimental evidence that supports ecdysone receptor as a potential target in the development of vector control measures targeting An. funestus.
Comparing the use of conventional and three-dimensional printing (3DP) in mandibular reconstruction
Authors: Truscott Ailis , Zamani Reza , Akrami Mohammad
Published: March 2022

Background

There are a number of clinical disorders that require mandibular reconstruction (MR). Novel three-dimensional (3D) printing technology enables reconstructions to be more accurate and beneficial to the patient. However, there is currently no evidence identifying which techniques are better suited for MR, based on the type of clinical disorder the patient has. In this study, we aim to compare 3D techniques with conventional techniques to identify how best to reconstruct the mandible based on the clinical cause that necessitates the reconstructive procedure: cancerous or benign tumours, clinical disorders, infection or disease and trauma or injury.

Methods

PubMed, Scopus, Embase and Medline were searched to identify relevant papers that outline the clinical differences between 3D and conventional techniques in MR. Data were evaluated to provide a clear outline of suitable techniques for surgery.

Results

20 of 2749 papers met inclusion criteria. These papers were grouped based on the clinical causes that required MR into four categories: malignant or benign tumour resection; mandibular trauma/injury and other clinical disorders.

Conclusions

The majority of researchers favoured 3D techniques in MR. However, due to a lack of standardised reporting in these studies it was not possible to determine which specific techniques were better for which clinical presentations.
H2O2-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs
Authors: Chen Youlu , Chen Zuoguan , Duan Jianwei , Gui Liang , Li Huiyang , Liang Xiaoyu , Tian Xinxin , Liu Kaijing , Li Yongjun , Yang Jing
Published: March 2022

Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs.

Graphical Abstract
Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing
Authors: Xia Wenzheng , Li Minxiong , Jiang Xingyu , Huang Xin , Gu Shuchen , Ye Jiaqi , Zhu Liaoxiang , Hou Meng , Zan Tao
Published: March 2022

Aged skin wounds heal poorly, resulting in medical, economic, and social burdens posed by nonhealing wounds. Age-related defects in repair are associated with reduced myofibroblasts and dysfunctional extracellular matrix (ECM) deposition. Bidirectional cell-cell communication involving exosome-borne cargo such as micro RNAs (miRs) has emerged as a critical mechanism for wound healing and aged tissue regeneration. Here we report that at the wound edge, aged fibroblasts display reduced migration and differentiation into myofibroblasts, with impaired ECM deposition, when compared with young tissue. Proper activation of fibroblasts to myofibroblasts may alleviate age-related defects in wound healing. Herein, an exosome-guided cell technique was performed to induce effective wound healing. Supplementing wounds with exosomes isolated from young mouse wound-edge fibroblasts (exosomesYoung) significantly improved the abundance of myofibroblasts and wound healing in aged mice and caused fibroblasts to migrate and transition to myofibroblasts in vitro. To determine the underlying mechanism, we found that exosomal transfer of miR-125b to fibroblasts inhibited sirtuin 7 (Sirt7), thus accelerating myofibroblast differentiation and wound healing in aged mice. Notably, after epidermal inhibition of miR-125b or overexpression of Sirt7 in fibroblasts, migration and myofibroblast transition were perturbed. Our findings thus reveal that miR-125b is transferred through exosomes from young fibroblasts to old fibroblasts contributes to promoting fibroblast migration and transition to counteract aging, suggesting a potential avenue for anti-aging interventions in wound healing.

Graphical Abstract
Using qualitative research to develop an elaboration of the TIDieR checklist for interventions to enhance vaccination communication: short report
Authors: Glenton Claire , Carlsen Benedicte , Winje Brita Askeland , Eilers Renske , Wennekes Manuela Dominique , Hoffmann Tammy C. , Lewin Simon ,   The VITAL Consortium
Published: March 2022

Background

The COVID-19 pandemic has led to an increased interest in communication with the public regarding vaccination. Our recent Cochrane qualitative evidence synthesis points to several factors that could influence the implementation and success of healthcare worker communication with older adults about vaccination. However, it is often difficult to assess whether factors identified as potentially important in qualitative studies have been considered in randomized trials because of poor trial reporting. We therefore decided to use our qualitative evidence synthesis findings to encourage better reporting of vaccination communication interventions in trials by developing an elaboration of the TIDieR (Template for Intervention Description and Replication) checklist for intervention reporting.

Methods

We examined the findings from our Cochrane qualitative evidence synthesis on healthcare workers’ perceptions of and experiences with communicating about vaccination with adults over the age of 50 years. We identified factors that could influence the implementation and uptake, and thereby the effectiveness, of vaccination communication interventions. We then drafted a list of the information elements we would need from trial reports to assess whether these factors had been considered in the development of the interventions evaluated in these trials. Finally, we compared our list of information elements to the TIDieR checklist items. We were able to align all of our information elements with the TIDieR items. However, for several of the TIDieR items, we developed a more detailed description to ensure that relevant information would be captured sufficiently in trial reports.

Results

We developed elaborations for the following TIDieR items: “Why” (item 2), “What—materials” (item 3), “Who provided” (item 5), “How” (item 6), “Where” (item 7) and “Tailoring” (item 9).

Conclusions

Both qualitative research and trials of intervention effectiveness are critical to furthering our understanding of what works, where, for whom and through which mechanisms. However, a key ingredient for developing this understanding is adequate reporting of intervention design, content and implementation in randomized trials. We hope that this elaboration of the TIDier checklist will improve reporting of interventions in trials focused on vaccine communication with older adults, and thereby enhance the usability of this research for developing future communication strategies.
METTL14-mediated N6-methyladenosine modification of ITGB4 mRNA inhibits metastasis of clear cell renal cell carcinoma
Authors: Liu Zhuonan , Sun Tianshui , Piao Chiyuan , Zhang Zhe , Kong Chuize
Published: March 2022

Background

Integrin β4 (ITGB4) participates in tumorigenesis and progression of several malignancies, but its role and related mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear.

Methods

Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry were used to detect mRNA and protein levels of relevant genes. Biological functions of ITGB4 and methyltransferase-like 14 (METTL14) were determined by in vitro and in vivo experiments. The levels of N6-methyladenosine (m6A) in ccRCC tissues and adjacent normal tissues were calculated via total RNA m6A quantification assay. The m6A modification of ITGB4 was demonstrated via m6A RNA immunoprecipitation (MeRIP), RIP and luciferase reporter assays.

Results

ITGB4 was significantly overexpressed in ccRCC tissues and high level of ITGB4 predicted poor prognosis as well as metastasis. Functionally, ITGB4 stimulated ccRCC cell migration and invasion in vitro and metastasis in vivo with epithelial–mesenchymal transition (EMT) strengthened. Mechanically, the total levels of m6A were reduced in ccRCC tissues. METTL14, a favorable factor for ccRCC patients’ prognosis, facilitated m6A modification on ITGB4 3′UTR and subsequently accelerated ITGB4 mRNA degradation, leading to its declined expression. Furthermore, the METTL14-mediated inhibition of ITGB4 expression was dependent on the YTH domain family protein 2 (YTHDF2), which acted as an m6A reader to bind to ITGB4 mRNA and to promote its decay. In addition, we demonstrated that knockdown of METTL14 promoted ccRCC cell migration, invasiveness and metastasis as well as stimulating the EMT process and the PI3K/AKT signal by overexpressing ITGB4.

Conclusion

Our study reveals that METTL14 inhibits ITGB4 expression via m6A modification to attenuate metastasis and EMT of ccRCC cells, suggesting the METTL14/ITGB4 axis as a potential prognostic biomarker and therapeutic target for ccRCC.
Combination of artesunate and WNT974 induces KRAS protein degradation by upregulating E3 ligase ANACP2 and β-TrCP in the ubiquitin–proteasome pathway
Authors: Gong Rui-Hong , Chen Minting , Huang Chunhua , Wong Hoi Leong Xavier , Kwan Hiu Yee , Bian Zhaoxiang
Published: March 2022

Background

KRAS mutation is one of the dominant gene mutations in colorectal cancer (CRC). Up to present, targeting KRAS for CRC treatment remains a clinical challenge. WNT974 (LGK974) is a porcupine inhibitor that interferes Wnt signaling pathway. Artesunate (ART) is a water-soluble semi-synthetic derivative of artemisinin.

Methods

The synergistic effect of ART and WNT974 combination in reducing CRC cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RT-PCR was utilized for the mRNA levels of KRAS, CUL7, ANAPC2, UBE2M, RNF123, SYVN1, or β-TrCP. Western blot assay was utilized for the protein levels of NRAS, HRAS, KRAS, ANAPC2, β-TrCP, GSK-3β, p-Akt (Ser473), t-Akt, p-PI3K (Tyr458), t-PI3K, p-mTOR (Ser2448), t-mTOR. Xenograft mouse model assay was performed for the anti-CRC effect of combination of ART and WNT974 in vivo. IHC assay was utilized for the levels of KRAS, β-TrCP, GSK-3β or ANAPC2 in tumor tissues.

Results

Our study shows that the combination of WNT974 and ART exhibits synergistic effect in reducing CRC growth. The combination treatment significantly reduces KRAS protein level and activity in CRC cells. Interestingly, the combination treatment increases E3 ligases ANAPC2 expression. Our data show that overexpression of ANAPC2 significantly reduces KRAS protein levels, which is reversed by MG132. Knockdown of ANAPC2 in CRC abolishes the combination treatment-reduce KRAS expression. Besides, the treatment also increases the expressions of GSK-3β and E3 ligase β-TrCP that is known to degrade GSK-3β-phosphorylated KRAS protein. Knockdown of β-TrCP- and inhibition of GSK-3β abolish the combination treatment-induce KRAS ubiquitination and reduction in expression. Last but not least, combination treatment suppresses PI3K/Akt/m-TOR signaling pathway.

Conclusions

Our data clearly show that the combination treatment significantly enhances KRAS protein degradation via the ubiquitination ubiquitin–proteasome pathway, which is also demonstrated in xenograft mouse model. The study provides strong scientific evidence for the development of the combination of WNT974 and ART as KRAS-targeting therapeutics for CRC treatment.