Introduction: The creation of the “open cavity” to clear cholesteatoma results in significant morbidity in over a third of patients. Various biological and non-biological materials have been used to reduce or obliterated these mastoid cavities. Materials and Methods: This study reports the technique and results of using hydroxyapatite granules with a pericranial flap to obliterate troublesome cavities. Results: 50 mastoid obliterations were performed in 48 patients. 94% no longer required water precautions 2 months post-operatively and may use conventional hearing aids. Discussion: This technique improves patients’ quality of life and can enable discharge of patients previously reliant on ENT services.
Global warming is already affecting plant phenology, growth and reproduction. A wide range of evidence indicates warming effects on reproductive and vegetative traits, as well as phenology, but seldom do studies assess these traits in concert and across the whole of a plant's life cycle, particularly in wild species. Further, while there is evidence that these effects vary between species little is known about the extent of within-species variation for plant persistence under future warming scenarios. We assessed trait variation in response to warming in Oreomyrrhis eriopoda, an Australian native montane herb, in which within-species variation in germination strategy and growth characteristics has been demonstrated. We quantified associations between developmental trajectories and population-level variation in germination timing and examined whether the next-generation traits are altered by maternal growth conditions. Warming effects were expressed in different traits during different developmental stages. The effect of warming varied as a function of germination strategy, but germination strategy itself was conserved across generations. Thus, we conclude that understand the response of wild species to warming takes a whole-of-life perspective and attention to ecologically significant patterns of within species variation.
Background: Successful active surveillance for infectious disease leads to increased case detection and better management outcomes. Because of that, the National Tuberculosis Programme (NTP), Ghana introduced Symptoms-Based Screening (SBS) Tool for TB case finding. Despite these efforts, Ghana has not achieved the 10% target of TB screening in all out-patient departments attendees as recommended by the NTP. Therefore, this study determined the challenges and limitations of the SBS Tool used for active tuberculosis case finding in Ghana. Methods: This study targeted presumptive TB patients resident in Ho Municipality, Ghana. Presumptive TB patients, recruited from Ho Teaching and Ho Municipal Hospitals, were screened with the SBS tool and presumed TB patients tested for M. tuberculosis using microscopy and positive samples confirmed by geneXpert technique. Also health personnel were interviewed to assess the user-friendliness, challenges and limitations associated with the SBS tool. Chi square association of categorical data was done by STATA version 14.1. P-values <0.05 was considered statistically significant. Results: From both hospitals, 636 presumptive patients and 24 health workers participated in this study. Of the total patients screened, 1.73% had active tuberculosis. Coughing for > 2 weeks (x2=24.8; p<0.05); chest pains (x2=28.3; p<0.01) and night sweat (x2=34.8; p<0.05) associated significantly with M. tuberculosis infection status. The main challenge associated with the SBS tool was its unfriendliness for administration while lack of enough indicators to identify other vulnerable individuals to TB (diabetics, cigarette smokers, alcoholics, immunocompromised and malnourished individuals) limited the sensitivity of the tool. Conclusion: The SBS tool was found not to be sensitive enough to identify infected cases. Inclusion of signs and symptoms of diabetes, immuno-suppression and malnutrition in the current tool and subsequent training of all relevant health personnel on the use of the tool could contribute to increase the sensitivity of the tool.
Stem cell-derived extracellular vesicles (EVs) have shown great promise in the field of regenerative medicine and tissue engineering. Recently, human bone marrow-derived mesenchymal stem cell (BMSC)-derived EVs have been considered for bone tissue engineering applications. In this study, we evaluated the osteogenic capability of placental stem cell (PSC)-derived EVs and compared them to the well-characterized BMSC-derived EVs. EVs were extracted from three designated time points (0, 7, and 21 days) after osteogenic differentiation. The results showed that the PSC-derived EVs had much higher protein and lipid concentrations than EVs derived from BMSCs. The extracted EVs were characterized by observing their morphology and size distribution before utilizing next-generation sequencing to determine their miRNA profiles. It was identified that 306 miRNAs within the EVs, of which 64 were significantly expressed in PSC-derived EVs that related to osteogenic differentiation. In vitro osteogenic differentiation study indicated that the late-stage (21-day extracted) derived EVs higher osteogenic enhancing capability when compared to the early-stage derived EVs. We demonstrated that EVs derived from PSCs could be a new source of EVs for bone tissue engineering applications.
Background and Purpose. Since the onset of COVID-19 many clinical trials of drugs and/or vaccines are continuing and new ones are introduce daily. Yet the international research process failed to develop a preventative vaccine or potent therapeutic drugs for relieving the severity of the disease. Therefore, at present the best recommendation to people to slow the spread of the disease is; please stay at home and maintain social distancing! Experimental approach. Many aspects of pharmacotherapeutic mechanism of action of some previously approved drugs with anti-inflammatory effects, such as colchicine, in various disorders is not fully understood. Therefore, many potential therapeutic uses for these drugs and its analogues can be imagined. In this hypothesis article, an attempt has been made to evaluate some potential therapeutic effects of colchicine that may be benefit against COVID-19. Key Results. Prophylactic therapy with colchicine regulates the innate inflammatory response by blocking intracellular signaling pathways. This can inhibit respiratory alveolar destruction following COVID-19 pneumonia, which is the main cause of ARDS and death in these patients. Conclusion and Implications Since the macrophage and granulocytes are the main pro-inflammatory mediators in the lung, it seems application of therapeutic doses of colchicine, before the onset of respiratory problems, will protect the lung against severe damages and respiratory failure in COVID-19 patients. Obviously, many clinical trials are required to prove the validity of this claim.
Nitrogen use efficiency (NUE) is an important and complex crops trait and its improvement represents a strategy to maintain high yield reducing N-supply. We report the genome-wide transcriptomic analysis of four eggplants contrasting for NUE to identify key genes related to the NUE pathway, after short- and long-term low-N exposure, in both root and shoot. Co-expression Gene Networks (CGN) analysis permitted to identify up-regulated differential expressed genes (DEGs) involved in the light reaction pathway, the biological processes response to inorganic substance, abiotic stimulus and cellular response to nitrogen starvation in high NUE genotypes. Some transcription factor (TF) were up-regulated in the N-use efficient genotypes, in particular, WRKY33 showed a significant up-regulation triggering the higher expression of 21 genes cluster including other TFs, many of which associated to N-metabolism. To validate our results, an independent de novo experiment including two other NUE-contrasting genotypes, at both low and high N supply, was carried out. Interestingly, the high significant WRKY33 expression and its cluster were confirmed in the high NUE genotypes at low-N supply. Moreover, the WRKY33 role was confirmed in Arabidopsis as the 35S::AtWRKY33 over expressing line showed a more competitive root system able to uptake more efficiently N from the soil.
We argue the advantages of field-based learning experiences for undergraduates, the societal imperative for training the next generation of field biologists, and the opportunity to increase the reach of field education dictate that we must meet the challenges of delivering field experiences in the context of a distanced educational environment. We report on our experiences as faculty and students in a spring 2020 Field Ornithology course adapted for remote delivery with an example of a student-centered framework for supporting independent field study. Feedback from students and instructors in this course indicate that remote field instruction is both possible and desirable. We suggest that an instruction model involving guided, independent field study can yield strong learning outcomes and promote self-directed inquiry. Based on reflections of the challenges and successes of our experiences, we provide an prompts for a for assessing the feasibility and desirability of proceeding with field-based education in a distanced environment with an emphasis on supporting student success.
Rational, Aims and Objectives: Prolonged symptoms after a mTBI, known as Post-Concussion Syndrome (PCS), remains a challenging area of rehabilitation. Evidence shows that an active approach can improve prognosis, however PCS is a multifaceted condition with many comorbidities and large variety in patient response. This study investigated the use of submaximal aerobic exercise and body awareness therapy, and the influence on symptoms in PCS cases, viewed through the lens of evidence-based practice (EBP). Method: Four cases were separated into two case studies. Cases in Study A received an aerobic exercise protocol consisting of 8 individual sessions distributed twice a week over 4 weeks, with additional cervical endurance training. Cases in Study B received a body awareness therapy protocol consisting of 6 guided practices distributed twice a week over 3 weeks. Using method triangulation, both quantitative and qualitative data were gathered through the use of the Rivermead Post-Concussion Questionnaire (RPQ) and semi-structured interviews, as well as the Craniocervical Flexion Test (CCFT) in Study A, and the Short Form-36v2 (SF-36) questionnaire in study B. Lastly, research evidence on PCS was included to contextualize cases. Results: Both cases in Study A showed marked improvements in their RPQ scores, but only one showed improvement in the CCFT. In Study B, one case improved in RPQ score and in the mental component of SF-36v2, while the other case did not experience any significant change. All cases expressed positive associations with the interventions during the interviews. Conclusion: These results illustrate how an active and individualized approach can represent important qualities that can be applied to further and larger studies. Based on the results and discussion of this paper, relevant findings and suggestions are summarized in a modified EBP model, which may be of help to practitioners in dealing with PCS patients in the clinical practice.
BACKGROUND AND PURPOSE Anaplastic thyroid carcinoma (ATC) is the least common but most lethal of thyroid cancers despite various therapeutic options with limited efficacy. Some prognostic factors were identified in patients with ATC and a few patients survive for a relatively long time after modern intensive treatment. In order to help therapeutic decision-making, the purpose of this study was to develop a new prognostic score providing survival estimates in patients with ATC. METHODS Based on a multivariate analysis of 149 retrospectively analyzed patients diagnosed with ATC from 1968 to 2017 at a referral center, a propensity score was developed. A model was generated providing survival probability at 6 months and median overall survival estimates. RESULTS The median survival was 96 days. The overall survival rate was 35% at 6 months, 20% at 1 year and 13% at 2 years. Most of the patients (86%) died within 17 month, 17% died within the first month, 35% lived for 1–6 months and 47 % of the patients lived longer than 6 months after the initial consultation. The stepwise Cox regression revealed that the most appropriate death prediction model included metastatic spread, tumor size and age class as explanatory variables. This model made it possible to define three categories of patients with survival profiles which seems different: patients with no pejorative prognostic factor which had a survival probability at 6 months = 0,84 (95% CI: 0,69-1), patients with one or two pejoratives prognostics factors which have a survival probability at 6 months = 0,32 (95% CI: 0,22-0,46), and those with three pejoratives prognostics factors which had a survival probability at 6 months = 0,11 (95% CI: 0,018 - 0,71). CONCLUSION Distant metastasis, age and primary tumor size are strong independent factors that affect prognosis in patients with ATC. Using these significant pretreatment factors, we developed a score to predict survival in these poor prognosis patients in order to provide easy-to-use tools for clinical practice. External validation in an additional dataset is needed for further outlooks.
CAD/CAM complete dentures have shown to improve the fit and material strength than conventionally fabricated dentures, however there are no clinical protocols described for extreme residual ridge resorption. This report describes a combined workflow of conventional and novel techniques for CAD/CAM complete dentures fabrication for atrophic alveolar ridges.
This study aimed to evaluate the antitumor potential and cytotoxicity induction mechanisms of green synthesized AgCl-NPs and Ag/AgCl-NPs through image-based high content analysis method. The antitumor potential of AgCl-NPs and Ag/AgCl-NPs was evaluated in breast cancer BT-474 and MDA-MB-436 cell lines treated with 0-40 μg/mL AgCl-NPs or 0-12.5 μg/mL Ag/AgCl-NPs. Normal human retinal pigment epithelial 1 (RPE-1) cells were used for comparison. The growth rate of the RPE-1 cells treated with AgCl-NPs or Ag/AgCl-NPs was little affected, and no significant changes in cell viability were observed. In these cells, the nanoparticle treatments did not induce lysosomal damage, changes in reactive oxygen species (ROS) production or a reduction in the mitochondrial membrane potential. Moreover, the percentage of apoptotic cells was minimally affected, reaching a maximum of 3.51% of the population. The level of BT-474 and MDA-MB-436 cell proliferation was markedly decreased, and cell viability was reduced by 64.19 and 46.19% after treatment with AgCl-NPs and reduced by 98.36 and 82.29% after treatment with Ag/AgCl-NPs. The cells also showed a significant increase in ROS production and loss of mitochondrial membrane potential, which culminated in an increase in the percentage of apoptotic cells. BT-474 cells also presented lysosomal damage when treated with the highest concentrations of both nanoparticle types, and actin polymerization was observed after exposure to Ag/AgCl-NPs. Together, the results obtained show overall cytotoxic effects of both AgCl-NPs and Ag/AgCl-NPs towards breast cancer cells with negligible effects against healthy cells, which suggests their promising anticancer and biomedical applications.
The contamination of heavy metals (e.g., Hg, Pb, Cd and As) poses great risks to environment and human health. Rapid and simple detection of heavy metals of considerable toxicity in low concentration levels is an important task in biological and environmental analysis. Among the many convenient detection methods for heavy metals, DNA-inspired gold nanoparticles (AuNPs) (DNA-AuNPs) have been becoming a well-established approach, in which assembly/disassembly of AuNPs serves for colorimetric signaling of the recognition event between DNA and target heavy metals at the AuNP interface. This review focuses on the recent efforts of employing DNA to manipulate the interfacial properties of AuNPs, and summarizes the recent advances in the colorimetric detection of heavy metals. Beginning with the introduction of the fundamental aspects of DNA and AuNPs, three main strategies of constructing DNA-AuNPs with DNA binding-responsive interface are discussed, namely, crosslinking, electrostatics, and base pair stacking. Then, recent achievements in colorimetric biosensing of heavy metals based on the interfacial manipulation of DNA-AuNPs are surveyed and compared. Finally, conclusions and perspectives on the futuristic directions in the field are provided, including the evaluation of the pros and cons of the three strategies, with an expectation of providing a reference for researchers who works in the related field. It is also suggested that manipulation of the interface of DNA-AuNPs represent enormous potential in the pursuit of colorimetric biosensors for a range of analytes of interest.
As percentages of elderly people rise in many societies, age-related diseases have become more prevalent. Research interests have been shifting to delaying age-related disease by delaying or reversing aging itself. We use metformin and rapamycin, two drugs at the center of anti-aging drug research, as an entry point to talk about important molecular and genetic anti-aging mechanisms that have been extensively studied with them, such as mTOR, AMPK, and epigenetic modifications. We also present a number of observational studies, animal studies, and clinical trials to reflect the potential and actual effects of the mechanisms. At the end, we list remaining concerns that not only apply to researches around metformin and rapamycin but also future researches to explore other anti-aging pathways and therapeutics.
Environmental temperature serves a major driver for adaptive changes in wild organisms, however, its role in domestication has been less characterized. To uncover the mechanisms of cold tolerance in domestic animals, we sequenced genomes of 28 cattle at median coverage from warm and cold areas across China. By characterizing the population structure and demographic history, we identified two genetic clusters, i.e., northern and southern cattle groups, and a common historic population peak at 30 kilo years ago. Genome scan of cold tolerant breeds revealed genes that under selection sweeps enriched in thermogenesis related pathways. Specifically, we determined a substitution of PRDM16 (p.P779L) in north cattle, which maintains the formation of brown adipocytes through boosting expression of thermogenic related genes, indicating a vital role of this gene in cold tolerance. The findings provide a basis of genetic variations in domestic cattle that shaped by temperature environments and highlight a role of reverse mutation in livestock species.
In this study, we unveiled the lumped effects at the reach spatial scale over three decades in one of the braided rivers in the Qinghai-Tibet Plateau of China, the Upper Lancang River (ULR). Using Landsat images obtained in 13 years between 1989 and 2018, we extracted flowing and non-flowing channels, active channel widths (unvegetated bars and flowing channels), and calculated lateral shifting rates of the main channel for the 13 periods. We also developed an empirical equation between vegetation area (Av) calculated from the high-resolution ortho-photo derived from an Unmanned Aerial Vehicle survey and Normalized Difference Vegetation Index for pixels of the Landsat image obtained at the same time. This relationship allowed us to estimate Av for other 12 selected years. We found that (1) braiding intensity increases with low discharges, indicating that the ULR is a very well-connected braided system with groundwater providing a large set of aquatic habitats, (2) this braided system is very well-supplied and actively shifting in relation to peak flow and flood duration, and (3) The ULR supports a progressive vegetation encroachment, which seems to be linked to temperature rising. Our study showed several similar morphological patterns to those in other braided rivers, such as the ones observed in the European Alps but much more active, well-supplied and highly connected. These similarities suggest that similar morphodynamic processes might take effect in the braided rivers with very high elevations and potentially high spots of biodiversity, indicating the ULR may be a reference for this region similarly to the Tagliamento in the Alps, but it seems that this system can be very sensitive to global change due to vegetation encroachment following temperature rising and decreases of low flows.
Objectives: To assess a newly developed educational video about lumbar puncture (LP), in the parents’ native language, tailored to their social background, and whether it facilitates their consent for LP. Methods: The randomized, controlled trial was conducted at outpatient pediatric clinics at a teaching hospital, Riyadh, Saudi Arabia. The conventional arm used LP verbal explanation. The second group utilized a standardized video with similar information. Parents’ knowledge, perceived LP risks, and willingness to consent were measured, before and after the intervention. Results: We enrolled 201 parents, with similar baseline characteristics. Both groups had an increase in knowledge scores, with Wilcoxon signed-rank test showing significant knowledge gains (Verbal Explanation: W=2693, n=83, P<0.001, and Video: W=5538, n=117, P< 0.001). However, the conventional verbal counseling resulted in more consistent knowledge gain (SD=14.5) as compared to the video group (SD= 18.94). The video group reported higher perceived risk (Mean 8.2, SD 3.59) than the verbal group (mean 7.12, SD 2.51). The less-educated parents perceived higher LP risk after watching the video (P< 0.001). Conclusions: LP video education in parents’ native language is as effective as conventional verbal education for the informed consent, with the additional advantage of reproducibility and more illustrations. While videos could facillitate remote procedural consenting process during infectious disease outbreaks; however, this should be followed by direct verbal interaction with parents, to ensure their full understanding and address any further concerns.
A 39-year-old woman was admitted with right leg deep venous thrombosis (DVT). She was started on apixaban tablets but developed pulmonary embolism. The medical history showed sleeve gastrectomy. The failure of the antithrombotic drug shed light on the efficacy and pharmacodynamic changes of DOACs after bariatric surgery