Search results for: multisystemic therapy

Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

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Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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Authors: Simon B. N. Thompson

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Early indicator of neurological disease has been proposed by the expanded Thompson Cortisol Hypothesis which suggests that yawning is linked to rises in cortisol levels. Cortisol is essential to the regulation of the immune system and pathological yawning is a symptom of multiple sclerosis (MS). Electromyography activity (EMG) in the jaw muscles typically rises when the muscles are moved – extended or flexed; and yawning has been shown to be highly correlated with cortisol levels in healthy people. It is likely that these elevated cortisol levels are also seen in people with MS. The possible link between EMG in the jaw muscles and rises in saliva cortisol levels during yawning were investigated in a randomized controlled trial of 60 volunteers aged 18-69 years who were exposed to conditions that were designed to elicit the yawning response. Saliva samples were collected at the start and after yawning, or at the end of the presentation of yawning-provoking stimuli, in the absence of a yawn, and EMG data was additionally collected during rest and yawning phases. Hospital Anxiety and Depression Scale, Yawning Susceptibility Scale, General Health Questionnaire, demographic, and health details were collected and the following exclusion criteria were adopted: chronic fatigue, diabetes, fibromyalgia, heart condition, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. Significant differences were found between the saliva cortisol samples for the yawners, t (23) = -4.263, p = 0.000, as compared with the non-yawners between rest and post-stimuli, which was non-significant. There were also significant differences between yawners and non-yawners for the EMG potentials with the yawners having higher rest and post-yawning potentials. Significant evidence was found to support the Thompson Cortisol Hypothesis suggesting that rises in cortisol levels are associated with the yawning response. Further research is underway to explore the use of cortisol as a potential diagnostic tool as an assist to the early diagnosis of symptoms related to neurological disorders. Bournemouth University Research & Ethics approval granted: JC28/1/13-KA6/9/13. Professional code of conduct, confidentiality, and safety issues have been addressed and approved in the Ethics submission. Trials identification number: ISRCTN61942768. http://www.controlled-trials.com/isrctn/

Keywords: cortisol, electromyography, neurology, yawning

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Authors: S. Pathak, R. Lazarus

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A 25-year-old male HIV patient (CD4 cells 20/µL and HIV viral load 14200000 copies/ml) with a past medical history of duodenal ulcer, pneumocystis carinii pneumonia, oesophageal candidiasis presented with fever and a seizure to hospital. The only recent travel had been a religious pilgrimage from Singapore to Malaysia 5 days prior; during the trip he sustained skin abrasions. The patient had recently started highly active antiretroviral therapy 2 months prior. Clinical examination was unremarkable other than a temperature of 38.8°C and perianal warts. Laboratory tests showed a leukocyte count 12.5x109 cells/L, haemoglobin 9.4 g/dL, normal biochemistry and a C-reactive protein 121 mg/L. CT head and MRI head were unremarkable and cerebrospinal fluid analysis performed after a delay (due to technical difficulties) of 11 days was unremarkable. Blood cultures (three sets) taken on admission showed Gram-negative rods in the anaerobic bottles only at the end of incubation with culture result confirmed by molecular sequencing showing Helicobacter cinaedi. The patient was treated empirically with ceftriaxone for seven days and this was converted to oral co-amoxiclav for a further seven days after the blood cultures became positive. A Transthoracic echocardiogram was unremarkable. The patient made a full recovery. Helicobacter cinaedi is a gram-negative anaerobic fastidious organism affecting patients with comorbidity. Infection may manifest as cellulitius, colitis or as in this case as bloodstream infection – the latter is often attributed to faeco-oral infection. Laboratory identification requires prolonged culture. Therapeutic options may be limited by resistance to macrolides and fluoroquinolones. The likely pathogen inoculation routes in the case described include gastrointestinal translocation due to proctitis at the site of perianal warts, or breach of the skin via abrasions occurring during the pilgrimage. Such organisms are increasing in prevalence as our patient population ages and patients have multiple comorbidities including HIV. It may be necessary in patients with unexplained fever to prolong incubation of sterile sites including blood in order to identify this unusual fastidious organism.

Keywords: fastidious, Helicobacter cinaedi, HIV, immunocompromised

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Authors: Emel Sonmezer, Hayri Baran Yosmaoglu

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The negative impact of chronic pain syndromes on sexual function has been reported in several studies; however, the influences of treatment strategies on sexual dysfunction have not been evaluated widely. The aim of this study was to determine the effects of pelvic floor exercise on sexual dysfunction in female patients with chronic low back pain. Forty-two patient with chronic low back pain were enrolled this study. Subjects were divided into two groups. Group 1 received conventional physiotherapy consist of heat therapy, ergonomic education, William flexion exercise during 6 weeks. Group 2 received pelvic floor exercises in addition to conventional physiotherapy. Female Sexual Function Index (FSFI) was used for the assessment of sexual function. Pain intensity was assessed with Visual Analogue Scale. Quality of life was assessed with World Health Organization Quality of Life Scale. All measurements were taken before and after treatment. In conventional physiotherapy group; there were significant improvement in pain intensity (p= 0,003), physical health (p=0,011), psychological health (p=0,042) subscales of quality of life scale, arousal (p=0,042), lubrication (p=0,028) and pain (p= 0,034) subscales of FSFI. In additional pelvic floor exercise group; there were significant improvement in pain intensity (p= 0,005), physical health (p=0,012) psychological health (p=0,039) subscales of quality of life scale, arousal (p=0,024), lubrication (p=0,011), orgasm (p=0,035) and pain (p= 0,015) subscales and total score (p=0,016) of FSFI. Total FSFI score (p=0,025) and orgasm (p=0,017) subscale of FSFI were significantly higher for the additional pelvic floor exercise group than the conventional physiotherapy group.The outcome of this study suggested that conventional physiotherapy may contribute to improve pain, quality of life and some parameters of the sexual function in patients with low back pain. Although additional pelvic floor exercise did not reveal more treatment effect in terms of quality of life and pain intensity, it caused significant improvement in sexual function. It is recommended that pelvic floor exercise should be added to treatment programs in order to manage sexual dysfunction more effectively in patients with chronic low back pain.

Keywords: physiotherapy, chronic pain, sexual dysfunction, pelvic floor

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Authors: Abdul Qadir Jangda, Khadija Mariam, Usman Ahmed, Sharib Ahmed

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The Gafchromic EBT3 film has the characteristic of high spatial resolution, weak energy dependence and near tissue equivalence which makes them viable to be used for in-vivo dosimetry in External Beam and Brachytherapy applications. The aim of this study is to assess the smallest film dimension that may be feasible for the use in in-vivo dosimetry. To evaluate the viability, the film sizes from 3 x 3 mm to 20 x 20 mm were calibrated with 6 MV Photon and 6 MeV electron beams. The Gafchromic EBT3 (Lot no. A05151201, Make: ISP) film was cut into five different sizes in order to establish the relationship between absorbed dose vs. film dimensions. The film dimension were 3 x 3, 5 x 5, 10 x 10, 15 x 15, and 20 x 20 mm. The films were irradiated on Varian Clinac® 2100C linear accelerator for dose range from 0 to 1000 cGy using PTW solid water phantom. The irradiation was performed as per clinical absolute dose rate calibratin setup, i.e. 100 cm SAD, 5.0 cm depth and field size of 10x10 cm2 and 100 cm SSD, 1.4 cm depth and 15x15 cm2 applicator for photon and electron respectively. The irradiated films were scanned with the landscape orientation and a post development time of 48 hours (minimum). Film scanning accomplished using Epson Expression 10000 XL Flatbed Scanner and quantitative analysis carried out with ImageJ freeware software. Results show that the dose variation with different film dimension ranging from 3 x 3 mm to 20 x 20 mm is very minimal with a maximum standard deviation of 0.0058 in Optical Density for a dose level of 3000 cGy and the the standard deviation increases with the increase in dose level. So the precaution must be taken while using the small dimension films for higher doses. Analysis shows that there is insignificant variation in the absorbed dose with a change in film dimension of EBT3 film. Study concludes that the film dimension upto 3 x 3 mm can safely be used up to a dose level of 3000 cGy without the need of recalibration for particular dimension in use for dosimetric application. However, for higher dose levels, one may need to calibrate the films for a particular dimension in use for higher accuracy. It was also noticed that the crystalline structure of the film got damage at the edges while cutting the film, which can contribute to the wrong dose if the region of interest includes the damage area of the film

Keywords: external beam radiotherapy, film calibration, film dosimetery, in-vivo dosimetery

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Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin

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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.

Keywords: biodistribution, burn, flightless, systemic, fnAbs

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Authors: Getahun Nigusie

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: To assess incidence and predictors of mortality among HIV positive children on ART in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, Ethiopia

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Authors: Lakmali Anthony, Madeline Gillies

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Background Breast cancer (BC) is usually managed with surgical resection. Many outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO) such as Health-Related Quality of life (HRQoL) provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods Patients who had resection of BC in a regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Results Forty-six patients completed the survey. Clinically significant levels of FCR and emotional distress were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for BC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL for breast cancer. All psychosocial factors measured were associated with HRQoL. Conclusion HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative breast cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: breast cancer, surgery, quality of life, regional population

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Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Joanna Estkowska

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The Sensory Integration Method is aimed primarily at children with learning disabilities. It can also be used as a complementary method in treatment of children with cerebral palsy, autistic, mentally handicapped, blind and deaf. Autism is holistic development disorder that manifests itself in the specific functioning of a child. The most characteristic are: disorders in communication, difficulties in social relations, rigid patterns of behavior and impairment in sensory processing. In addition to these disorders may occur abnormal intellectual development, attention deficit disorders, perceptual disorders and others. This study was focused on the application sensory integration techniques in science education of autistic students. The lack of proper sensory integration causes problems with complicated processes such as motor coordination, movement planning, visual or auditory perception, speech, writing, reading or counting. Good functioning and cooperation of proprioceptive, tactile and vestibular sense affect the child’s mastery of skills that require coordination of both sides of the body and synchronization of the cerebral hemispheres. These include, for example, all sports activities, precise manual skills such writing, as well as, reading and counting skills. All this takes place in stages. Achieving skills from the first stage determines the development of fitness from the next level. Any deficit in the scope of the first three stages can affect the development of new skills. This ultimately reflects on the achievements at school and in further professional and personal life. After careful analysis symptoms from the emotional and social spheres appear to be secondary to deficits of sensory integration. During our research, the students gained knowledge and skills in the classroom of experience by learning biology, chemistry and physics with application sensory integration techniques. Sensory integration therapy aims to teach the child an adequate response to stimuli coming to him from both the outside world and the body. Thanks to properly selected exercises, a child can improve perception and interpretation skills, motor skills, coordination of movements, attention and concentration or self-awareness, as well as social and emotional functioning.

Keywords: autism spectrum disorder, science education, sensory integration, special educational needs

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Authors: Garima Singh, Kunal Malhotra

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Objective: The expansion of telehealth has been instrumental in increasing access to medical services, especially for underserved and rural communities. In 2020, 14 million patients received virtual care through telemedicine and the global telemedicine market is expected to reach up to $185 million by 2023. It provides a platform and allows a patient to receive primary care as well as specialized care using technology and the comfort of their homes. Telemedicine was particularly useful during COVID-pandemic and the number of telehealth visits increased by 5000% during that time. It continues to serve as a significant resource for patients seeking care and to bridge the gap between the disease and the treatment. Method: As per APA (American Psychiatric Association), Telemedicine is the process of providing health care from a distance through technology. It is a subset of telemedicine, and can involve providing a range of services, including evaluations, therapy, patient education and medication management. It can involve direct interaction between a physician and the patient. It also encompasses supporting primary care providers with specialist consultation and expertise. It can also involve recording medical information (images, videos, etc.) and sending this to a distant site for later review. Results: In our organization, we are using telepsychiatry and serving 25 counties and approximately 1.4 million people. We provide multiple services, including inpatient, outpatient, crisis intervention, Rehab facility, autism services, case management, community treatment and multiple other modalities. With project ECHO (Extension for Community Healthcare Outcomes) it has been used to advise and assist primary care providers in treating mental health. It empowers primary care providers to treat patients in their own community by sharing knowledge. Conclusion: Telemedicine has shown to be a great medium in meeting patients’ needs and accessible mental health. It has been shown to improve access to care in both urban and rural settings by bringing care to a patient and reducing barriers like transportation, financial stress and resources. Telemedicine is also helping with reducing ER visits, integrating primary care and improving the continuity of care and follow-up. There has been substantial evidence and research about its effectiveness and its usage.

Keywords: telehealth, telemedicine, access to care, medical technology

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Authors: Katharina Kargel, Frederic Vobbe

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Sexualized violence against children and adolescents using digital media poses particular challenges for practitioners with a focus on crisis intervention (social work, psychotherapy, law enforcement). The technical delimitation of violence increases the burden on those affected and increases the complexity of interdisciplinary cooperation. Urgently needed recommendations for practical action do not yet exist in Germany. Funded by the Federal Ministry of Education and Research, these recommendations for action are being developed in the HUMAN project together with science and practice. The presentation introduces the participatory approach of the HUMAN project. We discuss the application-oriented, casuistic approach of the project and present its results using the example of concrete case-based recommendations for Action. The participants will be presented with concrete prototypical case studies from the project, which will be used to illustrate quality criteria for crisis intervention in cases of sexualized violence using digital media. On the basis of case analyses, focus group interviews and interviews with victims of violence, we present the six central challenges of sexualized violence with the use of digital media, namely: • Diffusion (Ambiguities regarding the extent and significance of violence) , • Transcendence (Space and time independence of the dynamics of violence, omnipresence), • omnipresent anxiety (considering diffusion and transcendence), • being haunted (repeated confrontation with digital memories of violence or the perpetrator), • disparity (conflicts of interpretative power between those affected and the social environment) • simultaneity (of all other factors). We point out generalizable principles with which these challenges can be dealt with professionally. Dealing professionally with sexualized violence using digital media requires a stronger networking of professional actors. A clear distinction must be made between their own mission and the mission of the network partners. Those affected by violence must be shown options for crisis intervention in the context of the aid networks. The different competencies and the professional mission of the offers of help are to be made transparent. The necessity of technical possibilities for deleting abuse images beyond criminal prosecution will be discussed. Those affected are stabilized by multimodal strategies such as a combination of rational emotive therapy, legal support and technical assistance.

Keywords: sexualized violence, intervention, digital media, children and youth

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Authors: Xiuguo Zhao, Xudong Ren, Chen Su, Xinxi Xu, Fu Niu, Lingshuai Meng

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The respiratory diseases such as asthma, emphysema and bronchitis are connected with the air pollution and the number of these diseases tends to increase, which may attribute to the toxic aerosol deposition in human upper respiratory tract or in the bifurcation of human lung. The therapy of these diseases mostly uses pharmaceuticals in the form of aerosol delivered into the human upper respiratory tract or the lung. Understanding of airflow structures in human upper respiratory tract plays a very important role in the analysis of the “filtering” effect in the pharynx/larynx and for obtaining correct air-particle inlet conditions to the lung. However, numerical simulation based CFD (Computational Fluid Dynamics) technology has its own advantage on studying airflow structure in human upper respiratory tract. In this paper, a representative human upper respiratory tract is built and the CFD technology was used to investigate the air movement characteristic in the human upper respiratory tract. The airflow movement characteristic, the effect of the airflow movement on the shear stress distribution and the probability of the wall injury caused by the shear stress are discussed. Experimentally validated computational fluid-aerosol dynamics results showed the following: the phenomenon of airflow separation appears near the outer wall of the pharynx and the trachea. The high velocity zone is created near the inner wall of the trachea. The airflow splits at the divider and a new boundary layer is generated at the inner wall of the downstream from the bifurcation with the high velocity near the inner wall of the trachea. The maximum velocity appears at the exterior of the boundary layer. The secondary swirls and axial velocity distribution result in the high shear stress acting on the inner wall of the trachea and bifurcation, finally lead to the inner wall injury. The enhancement of breathing intensity enhances the intensity of the shear stress acting on the inner wall of the trachea and the bifurcation. If human keep the high breathing intensity for long time, not only the ability for the transportation and regulation of the gas through the trachea and the bifurcation fall, but also result in the increase of the probability of the wall strain and tissue injury.

Keywords: airflow structure, computational fluid dynamics, human upper respiratory tract, wall shear stress, numerical simulation

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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Authors: John Michael Weber

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The following research results spanned six months and 175 people addicted to some form of substance, from alcohol to heroin. One question was asked, and the answers were amazing and consistent. The following work is the detailed results of this writer’s answer to his own question and the 175 that followed. A constant pattern took shape throughout the bio-psycho-social assessments, these addicts had “first memories,” the memories were vivid and took place between the ages of three to six years old, to a person those first memories were traumatic. This writer’s personal search into his childhood was not to find an excuse for the way he became, but to explain the reason for becoming an addict. To treat addiction, these memories that have caused Post Traumatic Stress Disorder (PTSD), must be recognized as the catalyst that sparked a predisposition. Cognitive Behavioral Therapy (CBT), integrated with treatment specifically focused on PTSD, gives the addict a better chance at recovery sans relapse. This paper seeks to give the findings of first memories of the addicts assessed and provide the best treatment plan for such an addict, considering, the childhood trauma in congruence with treatment of the Substance Use Disorder (SUD). The question posed was concerning what their first life memory wa It is the hope of this author to take the knowledge that trauma is one of the main catalysts for addiction, will allow therapists to provide better treatment and reduce relapse from abstinence from drugs and alcohol. This research led this author to believe that if treatment of childhood trauma is not a priority, the twelve steps of Alcoholics Anonymous, specifically steps 4 and 5, will not be thoroughly addressed and odds for relapse increase. With this knowledge, parents can be educated on childhood trauma and the effect it has on their children. Parents could be mindful of the fact that the things they perceive as traumatic, do not match what a child, in the developmental years, absorbs as traumatic. It is this author’s belief that what has become the status quo in treatment facilities has not been working for a long time. It is for that reason this author believes things need to change. Relapse has been woven into the fabric of standard operating procedure and that, in this authors view, is not necessary. Childhood Trauma is not being addressed early in recovery and that creates an environment of inevitable relapse. This paper will explore how to break away from the status -quo and rethink the current “evidencebased treatments.” To begin breaking away from status-quo, this ends the Abstract, with hopes an interest has been peaked to read on.

Keywords: childood, trauma, treatment, addiction, change

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Authors: Itsuo Yokoyama, Rika Kikuti, Naoko Watabe

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Introduction: It has been known that chronic kidney disease (CKD) patients can benefit from physical exercise during dialysis therapy improving aerobic capacity, muscle function, cardiovascular function, and overall health-related quality of life. This study aimed to evaluate the effectiveness of dialysis rehabilitation. Materials and Methods: A total of 55 patients underwent two-hour resistance exercise training during each hemodialysis session for three consecutive months. Various routine clinical data were collected, including the calculation of the planar dimension of the muscle area in both upper legs at the level of the ischial bone. This area calculation was possible in 26 patients who had yearly plain abdominal computed tomography (CT) scans. DICOM files from the CT scans were used with 3D Slicer software for area calculation. An age and sex-matched group of 26 patients without dialysis rehabilitation also had yearly CT scans during the study period for comparison. Clinical data were compared between the two groups: Group A (rehabilitation) and Group B (non-rehabilitation). Results: There were no differences in basic laboratory data between the two groups. The average muscle area before and after rehabilitation in Group A was 212 cm² and 216 cm², respectively. In Group B, the average areas were 230.0 cm² and 225.8 cm². While there was no significant difference in absolute values, the average percentage increase in muscle area was +1.2% (ranging from -7.6% to 6.54%) for Group A and -2.0% (ranging from -12.1% to 4.9%) for Group B, which was statistically significant. In Group A, 9 of 26 were diabetic (DM), and 13 of 26 in Group B were non-DM. The increase in muscle area for DM patients was 4.9% compared to -0.7% for non-DM patients, which was significantly different. There were no significant differences between the two groups in terms of nutritional assessment, Kt/V, or incidence of clinical complications such as cardiovascular events. Considerations: Dialysis rehabilitation has been reported to prevent muscle atrophy by increasing muscle fibers and capillaries. This study demonstrated that muscle volume increased after dialysis exercise, as evidenced by the increased muscle area in the thighs. Notably, diabetic patients seemed to benefit more from dialysis exercise than non-diabetics. Although this study is preliminary due to its relatively small sample size, it suggests that intradialytic physical training may improve insulin utilization in muscle fiber cells, particularly in type II diabetic patients where insulin receptor function and signaling are altered. Further studies are needed to investigate the detailed mechanisms underlying the muscle hypertrophic effects of dialysis exercise.

Keywords: dialysis, excercise, muscle, hypertrophy, diabetes, insulin

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Authors: Larry O. Awo, George N. Duru

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There are growing public and mental health concerns over the availability of gambling platforms and shops in Nigeria and the high level of youth involvement in gambling. Early theorizing maintained that gambling involvement was driven by a quest for resource gains. However, evidence shows that the economic model of gambling tends to explain the involvement of the gambling business owners (sport lottery operators: SLOs) as most gamblers lose more than they win. This loss, according to the law of effect, ought to discourage decisions to gamble. However, the quest to recover losses has often initiated prolonged gambling sessions. Therefore, the need to investigate mental contemplations (such as counterfactual reasoning (upward versus downward) of what “would, should, or could” have been, and feeling of the illusion of control; IOC) over gambling outcomes as risk or protective factors in gambling decisions became pertinent. The present study sought to understand the differential contributions and conditional effects of upward versus downward counterfactual reasoning as pathways through which the association between IOC and gambling decisions of Nigerian youths (N = 120, mean age = 18.05, SD = 3.81) could be explained. The study adopted a randomized group design, and data were obtained by means of stimulus material (the Gambling Episode; GE) and self-report measures of IOC and Gambling Decision. One-way analysis of variance (ANOVA) result showed that participants in the upward counterfactual reasoning group (M = 22.08) differed from their colleagues in the downward counterfactual reasoning group (M = 17.33) on the decision to gamble, and this difference was significant [F(1,112) = 23, P < .01]. HAYES PROCESS macro moderation analysis results showed that 1) IOC and upward counterfactual reasoning were positively associated with the decision to gamble (B = 14.21, t = 6.10, p < .01 and B = 7.22, t = 2.07, p <.05, respectively), 2) downward counterfactual reasoning was negatively associated with the decision to gamble more to recover losses (B = 10.03, t = 3.21, p < .01), 3) upward counterfactual reasoning did not moderate the association between IOC and gambling decision (p > .05), and 4) downward counterfactual reasoning negatively moderated the association between IOC and gambling decision (B = 07, t = 2.18, p < .05) such that the association was strong at the low level of downward counterfactual, but wane at high levels of downward counterfactual reasoning. The implication of these findings is that IOC and upward counterfactual reasoning were risk factors and promoted gambling behavior, while downward counterfactual reasoning protects individuals from gambling activities. Thus, it is concluded that downward counterfactual reasoning strategies should be included in gambling therapy and treatment packages as it could diminish feelings of both IOC and negative feelings of missed positive outcomes and the urge to gamble.

Keywords: counterfactual reasoning, gambling cognition, gambling decision, Nigeria, youths

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Authors: Satwik Majumder, Dongyun Jung, Jennifer Ronholm, Saji George

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Bovine mastitis is the most common infectious disease in dairy cattle, with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health. In this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with three heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors. Phenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics, and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = +0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates, corroborating phenotype observations. This investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through milk and dairy products.

Keywords: antimicrobial resistance, E. coli, bovine mastitis, antibiotics, heavy-metals, efflux pump, ß-lactamase enzyme, biofilm, whole-genome sequencing

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Authors: Emanuela Zilli, Antonella Ruffatto, Davide Bonaldo, Stefano Bevilacqua, Tommaso Caputo, Luisa Fontana, Carmelina Saraceno, Antonio Sturaroo, Teodoro Sava, Antonio Madia

Abstract:

The new Hospital in Cittadella - ULSS 6 Euganea Health Trust, in the North-East of Italy (400 beds, project completion date in 2026), will partially take the place of the existing building. Interesting features have been suggested in order to project a modern, “environmental-friendly” and “people-friendly” building. Specific multidisciplinary meetings (involving stakeholders and professionals with different backgrounds) have been organized on a periodic basis in order to guarantee the appropriate implementation of logistic and organizational solutions related to eco-sustainability, integration with the context, and the concept of “design for all” and “humanization of care.” The resulting building will be composed of organic shapes determined by the external environment (sun movement, climate, landscape, pre-existing buildings, roads) and the needs of the internal environment (areas of care and diagnostic-treatment paths reorganized with experience gained during the pandemic), with extensive use of renewable energy, solar panels, a 4th-generation heating system, sanitised and maintainable surfaces. There is particular attention to the quality of the staff areas, which include areas dedicated to psycho-physical well-being (relax points, yoga gym), study rooms, and a centralized conference room. Outdoor recreational spaces and gardens for music and watercolour therapy will be included; atai-chi gym is dedicated to oncology patients. Integration in the urban and social context is emphasized through window placement toward the gardens (maternal-infant, mental health, and rehabilitation wards). Service areas such as dialysis, radiology, and labs have views of the medieval walls, the symbol of the city’s history. The new building has been designed to pursue the maximum level of eco-sustainability, harmony with the environment, and integration with the historical, urban, and social context; the concept of humanization of care has been considered in all the phases of the project management.

Keywords: environmental-friendly, humanization, eco-sustainability, new hospital

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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Diabetes Mellitus (DM) is commonly encountered metabolic disorder in clinical practice. An estimated 25 percent of DM patients develop foot problems. Foot ulceration and infection are one of the major causes of morbidity, hospitalization or even amputation. Objective: To isolate and identify bacterial pathogens in Diabetic Foot Ulcer (DFU) and to observe its antimicrobial sensitivity pattern. Methodology: A prospective study was conducted for a period of 9 months at the Department of Microbiology, GD Hospital & Diabetes Institute, Kolkata. 75 DFU patients were recruited in the study. Specimens for microbiological studies obtained from ulcer base were examined as gram stained smear and was cultured aerobically on Nutrient agar, Blood agar and MacConkey agar plates. Antimicrobial sensitivity test was performed by disc diffusion techniques according to CLSI guidelines. Result: In this study out of 75cases, 73% (55/75) were male and 27% (20/75) were females with mean (SD) age of 51.11(±10) years. Out of 75 pus cultures, 63(84%) showed growth of microorganism making total of 81 bacterial isolates with 71.42% of monomicrobial infection and 28.57% of polymicrobial infection. Out of 81 isolates 53(65.43%) were gram negative and 21(25.92%) were gram positive. E.coli was relatively common isolate 21(26%) followed by Staphylococcus aureus 15(18.5%), Klebsiella pneumonia 14(17.28%), Pseudomonas aeruginosa 12 (14.81%), Proteus spp. 3 (3.70%), and Enterococcus faecalis 6 (7.40%). 75% of Gram-negative microorganism were extended Beta-lactamase enzyme (ESBL) producer and around 20 % of Klebsiella and Proteus spp. were carbapenemase enzyme producer. Among Gram positive, around 50% of S.aureus was MRSA, sensitive only to Vancomycin, Teicoplanin & Linezolid. Conclusion: More prevalence of monomicrobial gram-negative bacteria than gram-positive bacteria in DFU was observed. This study emphasizes that Beta-Lactam group of antibiotics should not be the empirical treatment of choice for Gram-negative isolates; instead alternatives like Carbapenems, Amikacin could be a better option. On the other hand, Vancomycin and Linezolid are preferred for most of the infection with gram-positive aerobes. Continuous surveillance of resistant bacteria is required for empiric therapy.

Keywords: antibiotic resistant, antimicrobial susceptibility, diabetic foot ulcer, surveillance

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Authors: J. Wozniak-Holecka, T. Holecki, P. Romaniuk

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Spa facilities are being perceived as the ways of healing treatment in Poland and are guaranteed within the public financing. The universal health insurance (National Health Fund, NFZ), and the disability prevention programme held by Social Insurance Institution (ZUS) are the main sources of financing spa facilities. The dominant public payer of spa services is the NFZ. The Social Insurance Institution covers the cost of health treatment realized in spa facilities as medical rehabilitation, in the field of disability prevention. Health services delivered in the spa resorts are characterized by complexity, and the combination of various methods, typical for health prevention, education, balneotherapy, and physiotherapy. Healing with natural methods, believed to enhance the therapeutic effect, is also involved in health spa treatment. Regardless of the type of facility, each form of spa treatment includes health promotion, health education, prevention at all levels, including rehabilitation. The aim of the study was to determine the optimal organization of health education process. Its efficiency strongly depends on the type of service provider and the funding institution (NFZ vs ZUS). It results from the use of different measures of the effectiveness, the quality and the evaluation of the process being assessed by funding institutions. The methods of the study include a comparative and descriptive quantitative and qualitative analysis. In the empirical part, a questionnaire had been developed. It was then distributed among spa personnel, responsible directly for the health promotion, and among patients who are beneficiaries of health services in spa centers. The quantitative part of the study was based on interviews carried with the use of the online survey (CAWI: Computer-Assisted Web Interview), telephone survey (CATI: Computer-Assisted Telephone Interview) and a conventional questionnaire (PAPI: Paper over Pencil Interview). As a result of the conducted research, it was found that the effectiveness of health education activities in spa resort facilities in Poland is higher when the services are organized using structured tools for managerial control. This applies to formalized procedures implemented by one of the dominant payers covering costs of services (ZUS) and involves the application of health education as one of the mandatory elements of treatment, subjected to the process of control during the course of spa therapy and evaluation after it is completed.

Keywords: effectiveness, health education, public health system, spa treatment

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Authors: F. Pires, V. Geraldo, O. N. Oliveira Jr., M. Raposo

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Catechins are powerful antioxidants which have attractive properties useful for tumor therapy. Considering their antioxidant activity, these molecules can act as a scavenger of the reactive oxygen species (ROS), alleviating the damage of cell membrane induced by oxidative stress. The complexity and dynamic nature of the cell membrane compromise the analysis of the biophysical interactions between drug and cell membrane and restricts the transport or uptake of the drug by intracellular targets. To avoid the cell membrane complexity, we used biomimetic systems as liposomes and Langmuir monolayers to study the interaction between catechin and membranes at the molecular level. Liposomes were formed after the dispersion of anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)(sodium salt) (DPPG) phospholipids in an aqueous solution, which mimic the arrangement of lipids in natural cell membranes and allows the entrapment of catechins. Langmuir monolayers were formed after dropping amphiphilic molecules, DPPG phospholipids, dissolved in an organic solvent onto the water surface. In this work, we mixed epigallocatechin-3-gallate (EGCG) with DPPG liposomes and exposed them to ultra-violet radiation in order to evaluate the antioxidant potential of these molecules against oxidative stress induced by radiation. The presence of EGCG in the mixture decreased the rate of lipid peroxidation, proving that EGCG protects membranes through the quenching of the reactive oxygen species. Considering the high amount of hydroxyl groups (OH groups) on structure of EGCG, a possible mechanism to these molecules interact with membrane is through hydrogen bonding. We also investigated the effect of EGCG at various concentrations on DPPG Langmuir monolayers. The surface pressure isotherms and infrared reflection-absorption spectroscopy (PM-IRRAS) results corroborate with absorbance results preformed on liposome-model, showing that EGCG interacts with polar heads of the monolayers. This study elucidates the physiological action of EGCG which can be incorporated in lipid membrane. These results are also relevant for the improvement of the current protocols used to incorporate catechins in drug delivery systems.

Keywords: catechins, lipid membrane, anticancer agent, molecular interactions

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Authors: Sarai Guerrero, Lijia Liu

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Zinc gallogermanate (ZGGO) is a persistent phosphor that can emit in the near infrared (NIR) range once dopped with Cr³⁺ enabling its use for in-vivo deep-tissue bio-imaging. Such a property also allows for its application in cancer diagnosis and therapy. Given this, work into developing a synthetic procedure that can be done using common laboratory instruments and equipment as well as understanding ZGGO overall, is in demand. However, the ZGGO nanoparticles must have a size compatible for cell intake to occur while still maintaining sufficient photoluminescence. The nanoparticle must also be made biocompatible by functionalizing the surface for hydrophilic solubility and for high particle uniformity in the final product. Additionally, most research is completed on doped ZGGO, leaving a gap in understanding the base form of ZGGO. It also leaves a gap in understanding how doping affects the synthesis of ZGGO. In this work, the first step of optimizing the particle size via the crystalline size of ZGGO was done with undoped ZGGO using the organic acid, oleic acid (OA) for organic ligand-assisted biphasic hydrothermal synthesis. The effects of this synthesis procedure on ZGGO’s crystallinity were evaluated using Powder X-Ray Diffraction (PXRD). OA was selected as the capping ligand as experiments have shown it beneficial in synthesizing sub-10 nm zinc gallate (ZGO) nanoparticles as well as palladium nanocrystals and magnetite (Fe₃O₄) nanoparticles. Later it is possible to substitute OA with a different ligand allowing for hydrophilic solubility. Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) was used to investigate the surface of the nanoparticle to investigate and verify that OA had capped the nanoparticle. PXRD results showed that using this procedure led to improved crystallinity, comparable to the high-purity reagents used on the ZGGO nanoparticles. There was also a change in the crystalline size of the ZGGO nanoparticles. ATR-FTIR showed that once capped ZGGO cannot be annealed as doing so will affect the OA. These results point to this new procedure positively affecting the crystallinity of ZGGO nanoparticles. There are also repeatable implying the procedure is a reliable source of highly crystalline ZGGO nanoparticles. With this completed, the next step will be working on substituting the OA with a hydrophilic ligand. As these ligands effect the solubility of the nanoparticle as well as the pH that the nanoparticles can dissolve in, further research is needed to verify which ligand is best suited for preparing ZGGO for bio-imaging.

Keywords: biphasic hydrothermal synthesis, crystallinity, oleic acid, zinc gallogermanate

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Taku Numao, Kazu Amimoto, Tomoko Shimada, Kyohei Ichikawa

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Background: Unilateral spatial neglect (USN) is a common syndrome following damage to one hemisphere of the brain (usually the right side), in which a patient fails to report or respond to stimulation from the contralesional side. These symptoms are not due to primary sensory or motor deficits, but instead, reflect an inability to process input from that side of their environment. Prism adaptation (PA) is a therapeutic treatment for USN, wherein a patient’s visual field is artificially shifted laterally, resulting in a sensory-motor adaptation. However, patients with USN also tend to perceive a left-leaning subjective vertical in the frontal plane. The traditional PA cannot be used to correct a tilt in the subjective vertical, because a prism can only polarize, not twist, the surroundings. However, this can be accomplished using a head mounted display (HMD) and a web-camera. Therefore, this study investigated whether an HMD system could be used to correct the spatial perception of USN patients in the frontal as well as the horizontal plane. We recruited healthy subjects in order to collect data for the refinement of USN patient therapy. Methods: Eight healthy subjects sat on a chair wearing a HMD (Oculus rift DK2), with a web-camera (Ovrvision) displaying a 10 degree leftward rotation and a 10 degree counter-clockwise rotation along the frontal plane. Subjects attempted to point a finger at one of four targets, assigned randomly, a total of 48 times. Before and after the intervention, each subject’s body-centre judgment (BCJ) was tested by asking them to point a finger at a touch panel straight in front of their xiphisternum, 10 times sight unseen. Results: Intervention caused the location pointed to during the BCJ to shift 35 ± 17 mm (Ave ± SD) leftward in the horizontal plane, and 46 ± 29 mm downward in the frontal plane. The results in both planes were significant by paired-t-test (p<.01). Conclusions: The results in the horizontal plane are consistent with those observed following PA. Furthermore, the HMD and web-camera were able to elicit 3D effects, including in both the horizontal and frontal planes. Future work will focus on applying this method to patients with and without USN, and investigating whether subject posture is also affected by the HMD system.

Keywords: head mounted display, posture, prism adaptation, unilateral spatial neglect

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Authors: Agnieszka Rolinska, Marta Makara-Studzinska

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Introduction: In recent years, there has been an intensive development of research into the physiological relationships between the experienced stress and obesity. Moreover, strong chronic stress leads to the disorganization of a person’s activeness on various levels of functioning, including the behavioral and cognitive sphere (also in one’s diet). Aim: The present work addresses the following research questions: Is there a relationship between an increase in stress related to the disease and the need for the cyclicality of diabetologic education in gestational diabetes? Are there any differences in terms of the experienced stress during the last three months of pregnancy in women with gestational diabetes and in normal pregnancy between the patients with normal weight gains and those with abnormal weight gains? Are there any differences in terms of stress coping styles in women with gestational diabetes and in normal pregnancy between the patients with normal weight gains and those with abnormal weight gains? Method: The study involved pregnant women with gestational diabetes (treated with diet, without insulin therapy) and in normal pregnancy – 206 women in total. The following psychometric tools were employed: Perceived Stress Scale (PSS; Cohen, Kamarck, Mermelstein), Coping Inventory for Stressful Situations (CISS; Endler, Parker) and authors’ own questionnaire. Gestational diabetes mellitus was diagnosed on the basis of the results of fasting oral glucose tolerance test (75 g OGTT). Body weight measurements were confirmed in a diagnostic interview, taking into account medical data. Regularities in weight gains in pregnancy were determined according to the recommendations of the Polish Gynecological Society and American norms determined by the Institute of Medicine (IOM). Conclusions: An increase in stress related to the disease varies in patients with differing requirements for the cyclical nature of diabetologic education (i.e. education which is systematically repeated). There are no differences in terms of recently experienced stress and stress coping styles between women with gestational diabetes and those in normal pregnancy. There is a relationship between weight gains in pregnancy and the stress experienced in life as well as stress coping styles – both in pregnancy complicated by diabetes and in physiological pregnancy. In the discussion of the obtained results, the authors refer to scientific reports from English-language magazines of international range.

Keywords: diabetologic education, gestational diabetes, stress, weight gain in pregnancy

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Authors: Wing Chi Wong

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Globally, studying parents caring for children with attention deficit/ hyperactivity disorder (ADHD) is valuable in order to design measures in supporting those parents by health care providers and government. Such parents in Hong Kong seem to encounter detrimental stress and enormous difficulties which are exacerbated by the traditional Chinese culture, exclusion from social members and fiercely competitive educational system. However, seldom studies scrutinize this issue in Hong Kong. This article aims to review the literature regarding parents caring offsprings with ADHD in Hong Kong. Criteria were set for searching among published studies listed in various databases, including MEDLINE, CINCAHL, PsycINFO, ProQuest, Embase, Cochrane Library and Springer Link. Articles with words 'Attention Deficit Hyperactivity Disorder', 'parenting', 'parent', 'family', 'father', 'mother', 'care' in titles and abstracts were identified. Articles with all types of research designs and methods, regardless in English or Chinese, were included. They were limited to years between January 2008 and September 2018. Four relevant studies have resulted. Of them, two were exploratory studies, one was a qualitative study, and one was a survey. Samples were recruited from child psychiatric clinic, Child and Adolescent Mental Health Unit, or multiple family group therapy centres. Authors proclaimed that quality of life of those parents was usually low; particularly mothers perceived a higher stress than fathers; parenting barriers existed; conflicts were commonly raised in parent-child relationship resulting in probable maltreatment to children. Previous studies generally suggested the potential negative outcomes of parents caring children with ADHD. The types and effectiveness of interventions to those parents on relieving their tortures under Hong Kong context had not been explored and systematically evaluated. The scanty studies and existing understanding could not give a promising conclusion pertaining to the appropriate family intervention to parents living with children with ADHD. A stringent research design is necessary to establish evidence on the effectiveness of interventions for those families.

Keywords: attention deficit/ hyperactivity disorder, Hong Kong, parents, interventions

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