Search results for: emotionally focused couple therapy

Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Arman Kishan, Mark Haft, Kiyanna Thomas, Duc Nguyen, Dawn Laporte

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Objective: Patients receiving anticoagulation therapy frequently experience increased rates of postoperative complications. Presently, limited data exist regarding the outcomes of patients undergoing carpal tunnel release surgery (CTR) while on anticoagulation. Our objective is to examine and compare the occurrence of complications in patients on anticoagulation who underwent either endoscopic CTR (ECTR) or open CTR (OCTR) for CTS. Methods: The Trinet X database was utilized to retrospectively identify patients who underwent OCTR or ECTR while concurrently on anticoagulation. Demographic data, medical comorbidities, and complication rates were analyzed. We used multivariable analysis to identify differences in postoperative complications, including wound infection within 90 days, wound dehiscence within 90 days, and intraoperative median nerve injury between the two surgical methods in patients on anticoagulation. Results: A total of 10,919 carpal tunnel syndrome patients on anticoagulation were included in the study, with 9082 and 1837 undergoing OCTR and ECTR, respectively. Among patients on anticoagulation, those undergoing ECTR exhibited a significantly lower occurrence of 90-day wound infection (p < 0.001) and nerve injury (p < 0.001) compared to those who underwent OCTR. However, there was no statistically significant difference in the risk of 90-day wound dehiscence between the two groups (p = 0.323). Conclusion:  In prior studies, ECTR demonstrated reduced rates of postoperative complications compared to OCTR in the general population. Our study demonstrates that among patients on anticoagulation, those undergoing ECTR experienced a significantly lower incidence of 90-day wound infection and nerve injury, with risk reductions of 35% and 40%, respectively. These findings support using ECTR as a preferred surgical method for patients with CTS who are on anticoagulation therapy.

Keywords: endoscopic treatment of carpal tunnel syndrome, open treatment of carpal tunnel syndrome, postoperative complications in patients on anticoagulation, carpal tunnel syndrome

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Authors: Muhammad Isa Khan, Jalil Ur Rehman, Muhammad Afzal Khan Rao, James Chow

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Purpose: This study investigates the dose-volume variations in planning target volume (PTV) and organs-at-risk (OARs) using different collimator angles for smart arc prostate volumetric modulated arc therapy (VMAT). Awareness of the collimator angle for PTV and OARs sparing is essential for the planner because optimization contains numerous treatment constraints producing a complex, unstable and computationally challenging problem throughout its examination of an optimal plan in a rational time. Materials and Methods: Single arc VMAT plans at different collimator angles varied systematically (0°-90°) were performed on a Harold phantom and a new treatment plan is optimized for each collimator angle. We analyzed the conformity index (CI), homogeneity index (HI), gradient index (GI), monitor units (MUs), dose-volume histogram, mean and maximum doses to PTV. We also explored OARs (e.g. bladder, rectum and femoral heads), dose-volume criteria in the treatment plan (e.g. D30%, D50%, V30Gy and V38Gy of bladder and rectum; D5%,V14Gy and V22Gy of femoral heads), dose-volume histogram, mean and maximum doses for smart arc VMAT at different collimator angles. Results: There was no significance difference found in VMAT optimization at all studied collimator angles. However, if 0.5% accuracy is concerned then collimator angle = 45° provides higher CI and lower HI. Collimator angle = 15° also provides lower HI values like collimator angle 45°. It is seen that collimator angle = 75° is established as a good for rectum and right femur sparing. Collimator angle = 90° and collimator angle = 30° were found good for rectum and left femur sparing respectively. The PTV dose coverage statistics for each plan are comparatively independent of the collimator angles. Conclusion: It is concluded that this study will help the planner to have freedom to choose any collimator angle from (0°-90°) for PTV coverage and select a suitable collimator angle to spare OARs.

Keywords: VMAT, dose-volume histogram, collimator angle, organs-at-risk

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Authors: Isaac Mugume

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Since the beginning of the 21st century, climate change has been an issue due to the reported rise in global temperature and changes in the frequency as well as severity of extreme weather and climatic events. The changing climate has been attributed to rising concentrations of greenhouse gases, including environmental changes such as ecosystems and land-uses. Climatic projections have been carried out under the auspices of the intergovernmental panel on climate change where a couple of models have been run to inform us about the likelihood of future climates. Since one of the major forcings informing the changing climate is emission of greenhouse gases, different scenarios have been proposed and future climates for different periods presented. The global climate models project different areas to experience different impacts. While regional modeling is being carried out for high impact studies, bias correction is less documented. Yet, the regional climate models suffer bias which introduces uncertainty. This is addressed in this study by bias correcting the regional models. This study uses the Weather Research and Forecasting model under different representative concentration pathways and correcting the products of these models using observed climatic data. This study notes that bias correction (e.g., the running-mean bias correction; the best easy systematic estimator method; the simple linear regression method, nearest neighborhood, weighted mean) improves the climatic projection skill and therefore reduce the uncertainty inherent in the climatic projections.

Keywords: bias correction, climatic projections, numerical models, representative concentration pathways

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Authors: Hamitri-Guerfi Fatiha, Mekimene Lekhder, Madani Khodir, Youyou Ahcene

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Virgin olive oil is appreciated by consumers, the quality of the oil is regulated by the international olive oil council depends on its chemical composition, so, the correct packing conditions are a prerequisite to preserve oil color, flavor, and nutriments, from production to consumption. The contact of food with various materials of packaging, since the production, until their consumption constitutes one of the essential aspects of food safety (directive 76/833/CEE). In Algeria, plastic bottles, although, they are economic and light are largely used at packaging olive oil but not used in other countries. This is due to migration phenomena that can occur from these materials. Thus, the goal of this work is to examine the physicochemical behavior of the couple packaging plastic-oil during their exposure to three temperatures corresponding to the conditions of storage applied in Algeria. Like, it is difficult to compare blowers of bottles which are heavy engineering, it comes out from this study that the effect of heat, the absorption of water, the constraints of storage of acidity, as well as the composition of oil, the PET bottles showed a remarkable structural instability, this defect of quality was confirmed by the analysis of morphology by electronic scan microscopy. These bottles present a total migration significantly higher than the threshold of acceptance. Moreover, a metal contamination of oil by its packaging was confirmed by the spectroscopy of atomic absorption and a microanalysis. The differences observed between the results of the microanalysis applied and the mechanical characterizations of the various bottles are reported, showing the reality of the container-contents exchanges.

Keywords: interaction, stability, pet, virgin olive oil

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: Boukhalfa Djemouai, Belkadi Souhila, Safsaf Boubakeur

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To increase the profitability of the national herd so that it can meet the needs of the population, Algeria has proceeded to the introduction of new reproductive biotechnologies, including artificial insemination on natural heat, by induction and heat synchronization. This biotechnology uses the male way for the creation and dissemination of genetic progress. The study has focused on 30 goat kids and bucks local breed aged between 03 and 24 months, divided into 03 groups 03-06 months[Grp 1; n=9], 07-10 months [Grp 2; n=13] and 11-24 months [Grp 3; n=8], in order to determine the influence of age on testicular evolution by measurements of testis and scrotum, and the epididymis sperm parameters evaluation. These parameters are influenced by age variations (sperm and spermocytogram). The examined parameters have focused on testicular weight (grams), the scrotal circumference (cm), mass mobility (%), vitality rate (%), sperm concentration (x 109), and percentage of abnormal spermatozoa (%). The ANOVA reveals a significance effect of age on parameters: testis weight, scrotal circumference, sperm concentration, motility varying between high (p < 0.01) to very high significance (p < 0.001), while in viability and abnormalities no significance was observed between all groups. The value of these parameters increased significantly until the age of 02 years, while that of sperm abnormalities has increased in Grp2. The histological study of testicular development shows that the genetic spermatozoa function characterized by cell proliferation, which is more and more intense starting from the age of 05 months and can be considered as an age of puberty in the local breed goat Arbia and increases with animal age.

Keywords: kids and bucks, epididymis sperm, testicular measurements, Arbia breed

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Authors: Timea Harmath-Tánczos

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Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

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Authors: Fredrick O. Okumu, Mangaka C. Matoetoe

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Silver-platinum (Ag-Pt) bimetallic nanoparticles (NPs) with varying mole fractions (1:1, 1:3 and 3:1) were prepared by co-reduction of hexachloroplatinate and silver nitrate with sodium citrate. Upon successful formation of both monometallic and bimetallic (BM) core shell nanoparticles, cyclic voltammetry (CV) was used to characterize the NPs. The drop coated nanofilms on the GC substrate showed characteristic peaks of monometallic Ag NPs; Ag+/Ag0 redox couple as well as the Pt NPs; hydrogen adsorption and desorption peaks. These characteristic peaks were confirmed in the bimetallic NPs voltammograms. The following varying current trends were observed in the BM NPs ratios; GCE/Ag-Pt 1:3 > GCE/Ag-Pt 3:1 > GCE/Ag-Pt 1:1. Fundamental electrochemical properties which directly or indirectly affects the applicability of films such as; diffusion coefficient (D), electroactive surface coverage, electrochemical band gap, electron transfer coefficient (α) and charge (Q) were assessed using Randles - Sevcik plot and Laviron’s equations . High charge and surface coverage was observed in GCE/Ag-Pt 1:3 which supports its enhanced current. GCE/Ag-Pt 3:1 showed high diffusion coefficient while GCE/Ag-Pt 1:1 possessed high electron transfer coefficient that is facilitated by its high apparent heterogeneous rate constant relative to other BM NPs ratios. Surface redox reaction was determined as adsorption controlled in all modified GCEs. Surface coverage is inversely proportional to size; therefore the surface coverage data suggests that Ag-Pt 1:1 NPs have a small particle size. Generally, GCE/Ag-Pt 1:3 depicts the best electrochemical properties.

Keywords: characterization, core-shell, electrochemical, nanoparticles

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Authors: Lormaine Anne A. Branzuela, Elysa V. Largo, Monet Concepcion M. Detras, Neil C. Concibido

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The electricity demand is still increasing, and currently, the Philippine government is investigating the feasibility of operating the Bataan Nuclear Power Plant (BNPP) to address the country’s energy problem. However, the lack of process safety studies on BNPP focused on the effects of hazardous substances on the integrity of the structure, equipment, and other components, have made the plant operationalization questionable to the public. The three major nuclear power plant incidents – TMI-2, Chernobyl, and Fukushima – have made many people hesitant to include nuclear energy in the energy matrix. This study focused on the safety evaluation of possible operations of a nuclear power plant installed with a Pressurized Water Reactor (PWR), which is similar to BNPP. Failure Mode and Effects Analysis (FMEA) is one of the Process Hazard Analysis (PHA) techniques used for the identification of equipment failure modes and minimizing its consequences. Using the FMEA technique, this study was able to recognize 116 different failure modes in total. Upon computation and ranking of the risk priority number (RPN) and criticality rating (CR), it showed that failure of the reactor coolant pump due to earthquakes is the most critical failure mode. This hazard scenario could lead to a nuclear meltdown and radioactive release, as identified by the FMEA team. Safeguards and recommended risk reduction strategies to lower the RPN and CR were identified such that the effects are minimized, the likelihood of occurrence is reduced, and failure detection is improved.

Keywords: PHA, FMEA, nuclear power plant, bataan nuclear power plant

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Authors: Ahmed Gonnah, Omar Masoud, Mohamed Abdel-Wahab, Ahmed ElMosalamy, Abdulrahman Al-Naseem

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Introduction: Fibroadenomas are solid, mobile, and non-tender benign breast lumps, with the highest prevalence amongst young women aged between 15 and 35. Symptoms can include discomfort, and they can become problematic, particularly when they enlarge, resulting in many referrals for biopsies, with fibroadenomas accounting for 30-75% of the cases. Diagnosis is based on triple assessment that involves a clinical examination, ultrasound imaging and mammography, as well as core needle biopsies. Current management includes observation for 6-12 months, with the indication of definitive surgery, in cases that are older than 35 years or with fibroadenoma persistence. Serious adverse effects of surgery might include nipple-areolar distortion, scarring and damage to the breast tissue, as well as the risks associated with surgery and anesthesia, making it a non-feasible option. Methods: A literature search was performed on the databases EMBASE. MEDLINE/PubMed, Google scholar and Ovid, for English language papers published between 1st of January 2000 and 17th of March 2021. A structured protocol was employed to devise a comprehensive search strategy with keywords and Boolean operators defined by the research question. The keywords used for the search were ‘HIFU’, ‘High-Intensity Focused Ultrasound’, ‘Fibroadenoma’, ‘Breast’, ‘Lesion’. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Recently, a thermal ablative technique, High Intensity Focused Ultrasound (HIFU), was found to be a safe, non-invasive, and technically successful alternative, having displayed promising outcomes in reducing the volume of fibroadenomas, pain experienced by patients, and the length of hospitalization. Quality of life improvement was also evidenced, exhibited by the disappearance of symptoms, and enhanced physical activity post-intervention, in addition to patients’ satisfaction with the cosmetic results and future recommendation of the procedure to other patients. Conclusion: Overall, HIFU is a well-tolerated treatment associated with a low risk of complications that can potentially include erythema, skin discoloration and bruising, with the majority of this self-resolving shortly after the procedure.

Keywords: ultrasound, HIFU, breast, efficacy, side effects, fibroadenoma

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Authors: Hannah K. M. Tang, Muhammad Ateeq, Mark J. Lake, Badr Abdullah, Frederic A. Bezombes

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Based on a theoretical assessment of current literature, virtual reality (VR) could help to treat sporting injuries in a number of ways. However, it is important to obtain rehabilitation specialists’ perspectives in order to design, develop and validate suitable content for a VR application focused on treatment. Subsequently, a one-day observation and interview study focused on the use of VR for the treatment of lower limb musculoskeletal conditions in athletes was conducted at St George’s Park England National Football Centre with rehabilitation specialists. The current paper established the methods suitable for obtaining practitioner’s viewpoints through observation and interview in this context. Particular detail was provided regarding the method of qualitatively processing interview results using the qualitative data analysis software tool NVivo, in order to produce a narrative of overarching themes. The observations and overarching themes identified could be used as a framework and success criteria of a VR application developed in future research. In conclusion, this work explained the methods deemed suitable for obtaining practitioner’s viewpoints through observation and interview. This was required in order to highlight characteristics and features of a VR application designed to treat lower limb musculoskeletal injury of athletes and could be built upon to direct future work.

Keywords: athletes, lower-limb musculoskeletal injury, rehabilitation, return-to-sport, virtual reality

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Authors: Maha Salah Abdullah Ismail, Manal S. Ismail, Amir M. Saleh

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Reflexology treatment is a method for enhancing body relaxation. It is a widely recognized as an alternative therapy, effective for many health conditions. This study aimed to evaluate the effect of reflexology treatment on arterial blood gases among mechanically ventilated patients. A quasi-experimental (pre and post-test) research design was used. Research hypothesis was mechanically ventilated patients who will receive the reflexology treatment will have improvement in their arterial blood gases than those who will not. The current study was carried out in different Intensive Care Units at the Cairo University Hospitals. A purposeful sample of 100 adults’ mechanically ventilated patients was recruited over a period of three months of data collection. The participants were divided into two equally matched groups; (1) The study group who has received the routine care, in addition, two reflexology sessions on the feet, (2) The control group who has received only the routine care. One tool was utilized to collect data pertinent to the study; mechanically ventilated patients' data sheet that consists of demographic and medical data. Result: Majority (58% of the study group and 82% of the control group) were males, with mean age of 50.9 years in both groups. Patients who received the reflexology treatment significantly increase in the oxygen saturation pre second session (t=5.15, p=.000), immediate post sessions (t=4.4, p=.000) and post two hours (t= 4.7, p= .000). The study group was more likely to have lower PaO2 (F=5.025, p=.015), PaCo2 (F=4.952, p=.025) and higher HCo3 (F=15.211, p=.000) than the control group. Conclusion: This study results support the positive effect of reflexology treatment in improving some arterial blood gases among mechanically ventilated patients’ with the conventional therapy as in the study group there was increase in the oxygen saturation. In differences between groups there decrease PaO2, PaCo2 and increase HCo3 in the study group. Recommendation: Nurses should be trained how to demonstrate the foot reflexology among mechanically ventilated patients.

Keywords: arterial blood gases, foot, mechanical ventilated patient, reflexology

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Authors: Jennifer Nutton, Gayle Ployer, Ky Scott, Jenny Morgan

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Working in a circle within higher education creates a decolonial space of mutual respect, responsibility, and reciprocity that facilitates collaborative learning and deep connections among learners and instructors. This approach is beyond simply facilitating a group in a circle but opens the door to creating a sacred space connecting each member to the land, to the Indigenous peoples who have taken care of the lands since time immemorial, to one another, and to one’s own positionality. These deep connections not only center human knowledges and relationships but also acknowledges responsibilities to land. Working in a circle as a relational pedagogical praxis also disrupts institutional power dynamics by creating a space of collaborative learning and deep connections in the classroom. Inherent within circle work is to facilitate connections not just academically but emotionally, physically, culturally, and spiritually. Recent literature supports the use of online talking circles, finding that it can offer a more relational and experiential learning environment, which is often absent in the virtual world and has been made more evident and necessary since the pandemic. These deeper experiences of learning and connection, rooted in both knowledge and the land, can then be shared with openness and vulnerability with one another, facilitating growth and change. This process of beginning with the land is critical to ensure we have the grounding to obstruct the ongoing realities of colonialism. The authors, who identify as both Indigenous and non-Indigenous, as both educators and learners, reflect on their teaching and learning experiences in circle. They share a relational pedagogical praxis framework that has been successful in educating future social workers, environmental activists, and leaders in social and human services, health, legal and political fields.

Keywords: circle work, relational pedagogies, decolonization, distance education

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Authors: Stephanie P. Nigro

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The Exhale Breath Hold (EBH) technique presents a promising approach to enhance the precision and efficacy of External Beam Radiation Therapy (EBRT) for abdominal tumours, which include liver, pancreas, kidney, and adrenal glands. These tumours are challenging to treat due to their proximity to organs at risk (OARs) and the significant motion induced by respiration and physiological variations, such as stomach filling. Respiratory motion can cause up to 40mm of displacement in abdominal organs, complicating accurate targeting. While current practices like limiting fasting help reduce motion related to digestive processes, they do not address respiratory motion. 4DCT scans are used to assess this motion, but they require extensive workflow time and expose patients to higher doses of radiation. The EBH technique, which involves holding the breath in an exhale with no air in the lungs, stabilizes internal organ motion, thereby reducing respiratory-induced motion. The primary benefit of EBH is the reduction in treatment volume sizes, specifically the Internal Target Volume (ITV) and Planning Target Volume (PTV), as demonstrated by smaller ITVs when gated in EBH. This reduction also improves the quality of 3D Cone Beam CT (CBCT) images by minimizing respiratory artifacts, facilitating soft tissue matching akin to stereotactic treatments. Patients suitable for EBH must meet criteria including the ability to hold their breath for at least 15 seconds and maintain a consistent breathing pattern. For those who do not qualify, the traditional 4DCT protocol will be used. The implementation involves an EBH planning scan and additional short EBH scans to ensure reproducibility and assist in contouring and volume expansions, with a Free Breathing (FB) scan used for setup purposes. Treatment planning on EBH scans leads to smaller PTVs, though intrafractional and interfractional breath hold variations must be accounted for in margins. The treatment decision process includes performing CBCT in EBH intervals, with careful matching and adjustment based on soft tissue and fiducial markers. Initial studies at two sites will evaluate the necessity of multiple CBCTs, assessing shifts and the benefits of initial versus mid-treatment CBCT. Considerations for successful implementation include thorough patient coaching, staff training, and verification of breath holds, despite potential disadvantages such as longer treatment times and patient exhaustion. Overall, the EBH technique offers significant improvements in the accuracy and quality of abdominal EBRT, paving the way for more effective and safer treatments for patients.

Keywords: abdominal cancers, exhale breath hold, radiation therapy, respiratory motion

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Authors: Ruzanna Muradyan

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Medical data mining is a crucial field in contemporary healthcare that offers cutting-edge tactics with enormous potential to transform patient care. This abstract examines how sophisticated data mining techniques could transform the healthcare industry, with a special focus on how they might improve patient outcomes. Healthcare data repositories have dynamically evolved, producing a rich tapestry of different, multi-dimensional information that includes genetic profiles, lifestyle markers, electronic health records, and more. By utilizing data mining techniques inside this vast library, a variety of prospects for precision medicine, predictive analytics, and insight production become visible. Predictive modeling for illness prediction, risk stratification, and therapy efficacy evaluations are important points of focus. Healthcare providers may use this abundance of data to tailor treatment plans, identify high-risk patient populations, and forecast disease trajectories by applying machine learning algorithms and predictive analytics. Better patient outcomes, more efficient use of resources, and early treatments are made possible by this proactive strategy. Furthermore, data mining techniques act as catalysts to reveal complex relationships between apparently unrelated data pieces, providing enhanced insights into the cause of disease, genetic susceptibilities, and environmental factors. Healthcare practitioners can get practical insights that guide disease prevention, customized patient counseling, and focused therapies by analyzing these associations. The abstract explores the problems and ethical issues that come with using data mining techniques in the healthcare industry. In order to properly use these approaches, it is essential to find a balance between data privacy, security issues, and the interpretability of complex models. Finally, this abstract demonstrates the revolutionary power of modern data mining methodologies in transforming the healthcare sector. Healthcare practitioners and researchers can uncover unique insights, enhance clinical decision-making, and ultimately elevate patient care to unprecedented levels of precision and efficacy by employing cutting-edge methodologies.

Keywords: data mining, healthcare, patient care, predictive analytics, precision medicine, electronic health records, machine learning, predictive modeling, disease prognosis, risk stratification, treatment efficacy, genetic profiles, precision health

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Authors: Meshal Al-Samhan, Abdullah Al-Marshed

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Recently, there has been a tremendous increase in interest in nanotechnology applications and nanomaterials in the oilfield. In the last decade, the global increase in oil production resulted in large amounts of produced water, causing a significant problem for all producing countries and companies. This produced water deserves special attention and a study of its characteristics to understand and determine how it can be treated and later used for suitable applications such as water injection for Enhance Oil Recovery (EOR) without harming the environment. This work aims to investigate the prepared compatible mixed water (seawater and effluent water) response to nanoparticles for EOR water injection. The evaluation of different mix seawater/effluent water ratios (60/40,70/30) for their characteristics prior to nanofluid preparation using Inductive Couple Plasma (ICP) analysis, potential zeta test, and OLI software (the OLI Systems is a recognised leader in aqueous chemistry). This step of the work revealed the suitability of the water mix with a lower effluent-water ratio. Also, OLI predicted that the 60:40 mix needs to be balanced around temperatures of 70 ºC to avoid the mass accumulation of calcium sulfate and strontium sulfate. Later the prepared nanofluid was tested for interfacial tension (IFT) and wettability restoration in the sandstone rock; the Al2O3 nanofluid at 0.06 wt% concentration reduced the IFT by more than 16% with moderate water wet contact angle. The study concluded that the selected nanoparticle Al2O3 had demonstrated excellent performance in decreasing the interfacial tension with respect to the selected water mix type (60/40) at low nanoparticles wt%.

Keywords: nano AL2O3, sanstone, nanofluid, IFT, wettability

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Authors: Zena Ebrahim, Susan Woodhouse

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Previous research shows that mothers’ experiences of trauma are linked to their child’s later socioemotional functioning. However, the mechanisms involved are not well understood. One potential mediator is maternal insensitive responses to child distress. This study examined the link between maternal trauma, mothers’ responses to toddler distress, and toddlers’ socioemotional outcomes among a socioeconomically diverse sample of 110 mothers and their 12- to 35-month-old toddlers. It was hypothesized that a mother’s difficulty in responding sensitively to her child’s distress would mediate the relations between maternal trauma and child internalizing and externalizing behaviors. Two mediational models were tested to examine non-supportive responses to distress as a potential mediator of the relation between maternal trauma and toddler mental health outcomes; one model focused on predicting child internalizing symptoms and the other focused on predicting child externalizing symptoms. Measures included assessment of maternal trauma (Life Stressor Checklist-Revised), mothers’ responses to child distress (Coping with Toddlers’ Negative Emotions Scale), and toddler socioemotional functioning (Infant-Toddler Social and Emotional Assessment). Results revealed that the relations between maternal trauma and toddler symptoms (internalizing and externalizing symptoms) were mediated by maternal non-supportive response to child distress for both internalizing and externalizing domains of child mental health. Findings suggest the importance of early intervention for trauma-exposed mothers and target areas for parenting interventions.

Keywords: trauma, parenting, child mental health, transgenerational effects of trauma

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Authors: Kanika Naresh Singh, Uday Shankar

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Background: Human behaviours are influenced by drives. Sexual drive is one of them. Education regarding sexual behaviour plays a great role in shaping one’s attitude towards it. These days after attaining the age of puberty, adolescents are confused and feel shy to talk about it. In order to get information, they refer to various types of sources and these sources play a greater role in spreading awareness in the mass adolescent population. Sometimes it also leads to the building of myths and misconceptions. Due to increasing incidences of HIV/AIDS, RTIs/STIs and teenage pregnancies, there is a rising need to impart sex education. Aim: The aim of this research was to study the level of sexual awareness among the youth of Bihar and also study their sexual behaviour and sources of influence. It also aims to study the correlation between sexual awareness, behaviour and sources of sexual knowledge among youth in Bihar. Methods: The sample size for the project was 50 youth consisting of both boys and girls, in between the age group of 18 to 23 years from urban and semi-urban areas. The purposive sampling method was used in the research. The tools used were the Sexual Awareness Questionnaire and Sexual Behavior and Sources of Influence (SBSI) scale. The sexual Awareness Questionnaire was developed by Snell, having 35 items. A socio-demographic data sheet was also used. Results: The youth had poor sexual awareness. Internet and Friends were found to be the major source for gathering information. The youth of Bihar were less inclined towards resolving their doubts with their parents. There was a positive correlation between sexual awareness, behaviour and sources of knowledge. Conclusion: The youth of Bihar has poor sexual knowledge. Internet and Friends are major sources of information. Sex Education should be promoted as suggested by various institutions like World Health Organization United Nations. Psychiatrists and psychologists have a key leadership role in introducing these potentially emotionally challenging issues to the youth with consideration of psychosocial and cultural factors.

Keywords: sexual awareness, sexual behavior, sources of influence, youths, Bihar, India

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Authors: Sophia Cyril Vincent

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Background: As per the Indian Census 2011, there is nearly 104 million elderly population aged above 60 years (53 million females and 51 males), and the count is expected to be 173 million by the end of 2026. Nearly 5.5% of women and 1.5% of men are living alone.1 In India, even though it is the moral duty of the children to take care of aged parents, many elders are landing in old age homes due to the social transformation factors like mushrooming of nuclear families, migration of children, cultural echoes, differences in mindset and values. Nearly 728 old age homes are seen across the country, out of which 78 old age homes with approximately 3000 inmates are seen only in Bangalore2. The existing literature shows that elderly women residing in old age homes experience the challenges like- loneliness, health issues, rejection from children, grief, death anxiety, etc, which leads to mental and physical wellbeing in numerous and tangible ways3. Hence the best and cost-effective way to improve the meaning and quality of life among elderly females is logotherapy, a type of psychotherapeutic analysis and treatment, motivating and driving force4 within the human experience to lead a decent life. Aim: The current research is aimed at studying the effectiveness of a logotherapy intervention on meaning and quality of life among elderly women of old age homes. Samples:200 women aged < 60 years and staying in the old age home for more than 1 year were randomly allocated to the control group and experimental group. Methodology: Using the Meaning in life questionnaire (MLQ)and the World health organization quality of life (WHOQOL) questionnaire, meaning and quality of life were assessed among both groups' women. Intensive Logotherapy and meaning in life program for five days were provided for the experimental group and the control group, with no treatment. Result: Under analysis. Conclusion: It is the right of the elderly woman to lead a happy and peaceful life till her death irrespective of the residing place. Hence, continuous monitoring and effective management are necessary for elderly women.

Keywords: quality of life, meaning of life, logo therapy, old age home

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Authors: Michael R. Taber, Kristin Stanec

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This paper presents year-two of a longitudinal study on implementing Possibility Books into undergraduate courses to develop a student's creativity mindset: tolerating ambiguity, willingness to risk failure, curiosity, and openness to embrace possibility thinking through unexpected connections. Courses involved in this research span disciplines in the natural and social sciences and the humanities. Year one of the project developed indices from which baseline data could be analyzed. The two significant indices ( > 0.7) were "creativity mindset" and "intentional interactions." Preliminary qualitative and quantitative data analysis indicated that students found the new pedagogical intervention as a safe space to learn new strategies, recognize patterns, and define structures through innovative notetaking forms. Possibility Books in Natural Science courses were designed to develop students' conceptualization of science and math. Using Possibility Books in all disciplines provided a space for students to practice divergent thinking (i.e.,Possibilities), convergent thinking (i.e., forms that express meaning), and risk-taking (i.e., the vulnerability associated with expression). Qualitative coding of open responses on a post-survey revealed two major themes: 1) Possibility Books provided a mind space for learning about self, and 2) provided a calming opportunity to connect concepts. Quantitative analysis indicated significant correlations between focused headspace and notetaking (r = 0.555, p < 0.001), focused headspace, and connecting with others (r = 0.405, p < 0.001).

Keywords: pedagogy, science education, learning methods, creativity mindsets

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Authors: K. Krizova

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This objective of this article is to present concrete that differs by the size of the aggregate used. The set of concrete contained six concrete recipes manufactured as traditional vibrated concrete containing identical basic components of concrete. The experiment focused on monitoring the resulting properties of hardened concrete, specifically the primary strength and modulus of the concrete elasticity and the developing parameters from 7 to 180 days were assessed.

Keywords: aggregate, cement, concrete, elasticity modulus

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Authors: Shawna Staud, Mary Kaye Scaramucci

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Objective: Rubber cup polishing has been a traditional method of preventative therapy in dental hygiene treatment. Newer methods such as air polishing have changed the way dental hygiene care is provided, yet this technique has not been embraced by students in the program nor by practitioners in the workforce. Students entering the workforce tend to follow office protocol and are limited in confidence to introduce technologies learned in the curriculum. This project was designed to help students gain confidence in newer skills and encourage private practice settings to adopt newer technologies for patient care. Our program recently introduced air polishing earlier in the program before the rubber cup technique to determine if students would embrace the technology to become leading-edge professionals when they enter the marketplace. Methods: The class of 2022 was taught the traditional method of polishing in the first-year curriculum and air polishing in the second-year curriculum. The class of 2023 will be taught the air polishing method in the first-year curriculum and the traditional method of polishing in the second-year curriculum. Pre- and post-graduation survey data will be collected from both cohorts. Descriptive statistics and pre and post-paired t-tests with alpha set at .05 to compare pre and post-survey results will be used to assess data. Results: This study is currently in progress, with a completion date of October 2023. The class of 2022 completed the pre-graduation survey in the spring of 2022. The post-gradation survey will be sent out in October 2022. The class of 2023 cohort will be surveyed in the spring of 2023 and October 2023. Conclusion: Our hypothesis is students who are taught air polishing first will be more inclined to adopt that skill in private practice, thereby embracing newer technology and improving oral health care.

Keywords: luggage handling system at world’s largest pilgrimage center

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Authors: Trevor E. Davis, Isaac Cassar, Yi-Kai Lo, Wentai Liu

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This study models the use of transcutaneous electrical nerve stimulation on skin with a disk electrode in order to simulate tissue damage. The current density distribution above a disk electrode is known to be a dynamic and non-uniform quantity that is intensified at the edges of the disk. The non-uniformity is subject to change through using various electrode geometries or stimulation methods. One of these methods known as edge-retarded stimulation has shown to reduce this edge enhancement. Though progress has been made in modeling the behavior of a disk electrode, little has been done to test the validity of these models in simulating the actual heat transfer from the electrode. This simulation uses finite element software to couple the injection of current from a disk electrode to heat transfer described by the Pennesbioheat transfer equation. An example application of this model is studying an experimental form of stimulation, known as edge-retarded stimulation. The edge-retarded stimulation method will reduce the current density at the edges of the electrode. It is hypothesized that reducing the current density edge enhancement effect will, in turn, reduce temperature change and tissue damage at the edges of these electrodes. This study tests this hypothesis as a demonstration of the capabilities of this model. The edge-retarded stimulation proved to be safer after this simulation. It is shown that temperature change and the fraction of tissue necrosis is much greater in the square wave stimulation. These results bring implications for changes of procedures in transcutaneous electrical nerve stimulation and transcutaneous spinal cord stimulation as well.

Keywords: bioheat transfer, electrode, neuroprosthetics, TENS, transcutaneous stimulation

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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Authors: Meless Gebrie Bore, Lin Perry, Xiaoyue Xu, Andargachew Kassa, Marilyn Cruickshank

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Background: Adolescents living with HIV (ALHIV) in Ethiopia face significant health challenges, particularly related to nutrition, which is essential for optimizing antiretroviral therapy (ART) outcomes. This population is vulnerable to nutritional deficiencies due to increased energy demands and the adverse effects of HIV, alongside rapid growth and low socio-economic status. Despite advances in ART, research on nutritional care for ALHIV in Ethiopia is limited. Integrated nutritional interventions are critical for improving health outcomes, yet comprehensive guidance is lacking. This study aimed to evaluate healthcare workers' practices in ART clinics, assess the nutritional status of ALHIV, and provide recommendations for enhancing nutritional care. Method: Cross-sectional surveys were conducted, recruiting 44 healthcare professionals and 384 ALHIV across ten public hospitals in Addis Ababa and Oromia regions. Participants were selected using purposive sampling for healthcare workers and proportionate random sampling for ALHIV engaged in ART services. Data was collected using a pre-tested structured questionnaire with quantitative and qualitative components facilitated by trained healthcare workers through the Kobo Toolbox program. Results: Findings revealed that while most healthcare workers conducted basic nutritional assessments, more sensitive methods were rarely used. Only 36.4% assessed dietary intake and 27.3% evaluated food security. Nutrition counseling was limited, with only 38.6% providing such services regularly. Health Care worker participants expressed dissatisfaction with the integration of nutrition services due to a lack of training and resources. Nutritional assessments revealed that 24.2% of ALHIV were classified as thin, 21.7% as stunted, and 34.9% as malnourished based on mid-upper arm circumference, with 19.4% experiencing severe acute malnutrition. These results highlight the urgent need and opportunities to improve nutritional support tailored to ALHIV-specific needs. Conclusion and Recommendations: Study findings identified evidence of substantial nutritional deficits and critical gaps in nutritional care for ALHIV in Ethiopian ART clinics. While basic assessment and counseling were generally practiced, limited use of more sensitive methods and inadequate integration of nutrition services hindered care effectiveness. To improve health outcomes, it is essential to enhance training for healthcare workers, develop standardized nutrition guidelines, and allocate resources effectively. Conducting further research with large, diverse samples and integrating comprehensive nutritional care alongside ART services will enable better matching of the nutritional needs of this vulnerable population.

Keywords: adolescents living with HIV(ALHIV), antiretroviral therapy (ART), HIV, Ethiopia, malnutrition, nutritional support, stunting, thinness

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Authors: Fleura Shkëmbi, Sevim Mustafa, Naim Fanaj

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Hypnosis, often known as cognitive therapy, is a sort of mind-body psychotherapy. A professional and certified hypnotist or hypnotherapist guides the patient into this extreme level of focus and relaxation during the session by utilizing verbal cues, repetition, and imagery. In recent years, hypnotherapy has gained popularity in the treatment of a variety of disorders, including anxiety and particular phobias. The term "phobia" is commonly used to define fear of a certain trigger. When faced with potentially hazardous situations, the brain naturally experiences dread. While a little dread here and there may keep us safe, phobias can drastically reduce our quality of life. In summary, persons who suffer from anxiety are considered to see particular environmental situations as dangerous, but those who do not suffer from anxiety do not. Hypnosis is essential in the treatment of anxiety disorders. Hypnosis can help patients minimize their anxiety symptoms. This broad concept has aided in the development of models and therapies for anxiety disorders such as generalized anxiety disorder, panic attacks, hypochondria, and obsessional disorders. Hypnosis techniques are supposed to be attentive and mental pictures, which is conceivable; this is why they're associated with improved working memory and visuospatial abilities. In this sense, the purpose of this study is to determine how effectively specific therapeutic methods perform in treating persons with anxiety and phobias. In addition to cognitive-behavioral therapy and other therapies, the approaches emphasized the use of therapeutic hypnosis. This study looks at the use of hypnosis and related psychotherapy procedures in the treatment of anxiety disorders. Following a discussion of the evolution of hypnosis as a therapeutic tool, neurobiological research is used to demonstrate the influence of hypnosis on the change of perception in the brain. The use of hypnosis in the treatment of phobias, stressful situations, and posttraumatic stress disorder is examined, as well as similarities between the hypnotic state and dissociative reactions to trauma. Through an extensive literature evaluation, this study will introduce hypnotherapy procedures that result in more successful anxiety and phobia treatment.

Keywords: anxiety, hypnosis, hypnotherapy, phobia, technique, state

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Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

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Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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Authors: Zahra R. Almansoor

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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.

Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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