Search results for: chronic hepatitis C screening

Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Sigal Gat-Lazer, Ronny Geva, Dan Ramon, Eitan Gur, Daniel Stein

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Introduction: Eating disorders (ED) are common psychopathologies which involve distorted body image and eating disturbances. Binge-purge eating disorders (B/P ED) are characterized by repetitive events of binge eating followed by purges. Patients with B/P ED behavior may be seen as impulsive especially when relate to food stimulation and affective conditions. The current study included innovative modification of the day-night task targeted to assess inhibitory control among patients with B/P ED. Methods: This prospective study included 50 patients with B/P ED during acute phase of illness (T1) upon their admission to specialized ED department in tertiary center. 34 patients repeated the study towards discharge to ambulatory care (T2). Treatment effect was evaluated by BMI and emotional questionnaires regarding depression and anxiety by the Beck Depression Inventory and State Trait Anxiety Inventory questionnaires. Control group included 36 healthy controls with matched demographic parameters who performed both T1 and T2 assessments. The current modification is based on the emotional day-night task (EDNT) which involves five emotional stimulation added to the sun and moon pictures presented to participants. In the current study, we designed the food-emotional modification day night task (F-EDNT) food stimulations of egg and banana which resemble the sun and moon, respectively, in five emotional states (angry, sad, happy, scrambled and neutral). During this computerized task, participants were instructed to push on “day” bottom in response to moon and banana stimulations and on “night” bottom when sun and egg were presented. Accuracy (A) and reaction time (RT) were evaluated and compared between EDNT and F-EDNT as a reflection of participants’ inhibitory control. Results: Patients with B/P ED had significantly improved BMI, depression and anxiety scores on T2 compared to T1 (all p<0.001). Task performance was similar among patients and controls in the EDNT without significant A or RT differences in both T1 and T2. On F-EDNT during T1, B/P ED patients had significantly reduced accuracy in 4/5 emotional stimulation compared to controls: angry (73±25% vs. 84±15%, respectively), sad (69±25% vs. 80±18%, respectively), happy (73±24% vs. 82±18%, respectively) and scrambled (74±24% vs. 84±13%, respectively, all p<0.05). Additionally, patients’ RT to food stimuli was significantly faster compared to neutral ones, in both cry and neutral emotional stimulations (356±146 vs. 400±141 and 378±124 vs. 412±116 msec, respectively, p<0.05). These significant differences between groups as a function of stimulus type were diminished on T2. Conclusion: Having to process food related content, in particular in emotional context seems to be impaired in patients with B/P ED during the acute phase of their illness and elicits greater impulsivity. Innovative modification using such procedures seem to be sensitive to patients’ illness phase and thus may be implemented during screening and follow up through the clinical management of these patients.

Keywords: binge purge eating disorders, day night task modification, eating disorders, food related stimulations

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Authors: Monika Soni, Chandra Bhattacharya, Siraj Ahmed Ahmed, Prafulla Dutta

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Dengue is now a globally important arboviral disease. Extensive vector surveillance has already established A.aegypti as a primary vector, but A.albopictus is now accelerating the situation through gradual adaptation to human surroundings. Global destabilization and gradual climatic shift with rising in temperature have significantly expanded the geographic range of these species These versatile vectors also host Chikungunya, Zika, and yellow fever virus. Biggest challenge faced by endemic countries now is upsurge in co-infection reported with multiple serotypes and virus co-circulation. To foster vector control interventions and mitigate disease burden, there is surge for knowledge on vector susceptibility and viral tolerance in response to multiple infections. To address our understanding on transmission dynamics and reproductive fitness, both the vectors were exposed to single and dual combinations of all four dengue serotypes by artificial feeding and followed up to third generation. Artificial feeding observed significant difference in feeding rate for both the species where A.albopictus was poor artificial feeder (35-50%) compared to A.aegypti (95-97%) Robust sequential screening of viral antigen in mosquitoes was followed by Dengue NS1 ELISA, RT-PCR and Quantitative PCR. To observe viral dissemination in different mosquito tissues Indirect immunofluorescence assay was performed. Result showed that both the vectors were infected initially with all dengue(1-4)serotypes and its co-infection (D1 and D2, D1 and D3, D1 and D4, D2 and D4) combinations. In case of DENV-2 there was significant difference in the peak titer observed at 16th day post infection. But when exposed to dual infections A.aegypti supported all combinations of virus where A.albopictus only continued single infections in successive days. There was a significant negative effect on the fecundity and fertility of both the vectors compared to control (PANOVA < 0.001). In case of dengue 2 infected mosquito, fecundity in parent generation was significantly higher (PBonferroni < 0.001) for A.albopicus compare to A.aegypti but there was a complete loss of fecundity from second to third generation for A.albopictus. It was observed that A.aegypti becomes infected with multiple serotypes frequently even at low viral titres compared to A.albopictus. Possible reason for this could be the presence of wolbachia infection in A.albopictus or mosquito innate immune response, small RNA interference etc. Based on the observations it could be anticipated that transovarial transmission may not be an important phenomenon for clinical disease outcome, due to the absence of viral positivity by third generation. Also, Dengue NS1 ELISA can be used for preliminary viral detection in mosquitoes as more than 90% of the samples were found positive compared to RT-PCR and viral load estimation.

Keywords: co-infection, dengue, reproductive fitness, viral quantification

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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Authors: Santhani M. Selveindran

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Background: Natural disasters are traumatic global events that are becoming increasing more common, with significant psychosocial impact on survivors. This impact results not only in psychosocial distress but, for many, can lead to psychosocial disorders and chronic psychopathology. While there are currently available interventions that seek to prevent and treat these psychosocial sequelae, their effectiveness is uncertain. The evidence-base is emerging with more primary studies evaluating the effectiveness of various psychosocial interventions for survivors of natural disasters, which remains to be synthesized. Aim of Review: To identify, critically appraise and synthesize the current evidence-base on the effectiveness of psychosocial interventions in preventing or treating Post-Traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD) and/or Generalized Anxiety Disorder (GAD) in adults and children who are survivors of natural disasters. Methods: A protocol was developed as a guide to carry out this review. A systematic search was conducted in eight international electronic databases, three grey literature databases, one dissertation and thesis repository, websites of six humanitarian and non-governmental organizations renowned for their work on natural disasters, as well as bibliographic and citation searching for eligible articles. Papers meeting the specific inclusion criteria underwent quality assessment using the Downs and Black checklist. Data were extracted from the included papers and analysed by way of narrative synthesis. Results: Database and website searching returned 3777 papers where 31 met the criteria for inclusion. Additional 2 papers were obtained through bibliographic and citation searching. Methodological quality of most papers was fair. Twenty-five studies evaluated psychological interventions, five, social interventions whereas three studies evaluated ‘mixed’ psychological and social interventions. All studies, irrespective of methodological quality, reported post-intervention reductions in symptom scores for PTSD, depression and/or anxiety and where assessed, reduced diagnosis of PTSD and MDD, and produced improvements in self-efficacy and quality of life. Statistically significant results were seen in 27 studies. However, three studies demonstrated that the evaluated interventions may not have been very beneficial. Conclusions: The overall positive results suggest that any psychosocial interventions are favourable and should be delivered to all natural disaster survivors, irrespective of age, country, and phase of disaster. Yet, heterogeneity and methodological shortcomings of the current evidence-base makes it difficult to draw definite conclusions needed to formulate categorical guidance or frameworks. Further, rigorously conducted research is needed in this area, although the feasibility of such, given the context and nature of the problem, is also recognized.

Keywords: psychosocial interventions, natural disasters, survivors, effectiveness

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Authors: Yongrong Liu, Xin Tang

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Background: Persistent atrial fibrillation is a common arrhythmia closely related to heart failure. Heart rate control is an essential strategy for treating persistent atrial fibrillation. Still, the understanding of the relationship between different heart rate control levels and the risk of heart failure rehospitalization is limited. Objective: The objective of the study is to determine the relationship between different levels of heart rate control in patients with persistent atrial fibrillation and the risk of readmission for heart failure. Methods: We conducted a retrospective dual-centre cohort study, collecting data from patients with persistent atrial fibrillation who received outpatient treatment at two tertiary hospitals in central and western China from March 2019 to March 2020. The collected data included age, gender, body mass index (BMI), medical history, and hospitalization frequency due to heart failure. Patients were divided into three groups based on their heart rate control levels: Group I with a resting heart rate of less than 80 beats per minute, Group II with a resting heart rate between 80 and 100 beats per minute, and Group III with a resting heart rate greater than 100 beats per minute. The readmission rates due to heart failure within one year after discharge were statistically analyzed using propensity score matching in a 1:1 ratio. Differences in readmission rates among the different groups were compared using one-way ANOVA. The impact of varying levels of heart rate control on the risk of readmission for heart failure was assessed using the Cox proportional hazards model. Binary logistic regression analysis was employed to control for potential confounding factors. Results: We enrolled a total of 1136 patients with persistent atrial fibrillation. The results of the one-way ANOVA showed that there were differences in readmission rates among groups exposed to different levels of heart rate control. The readmission rates due to heart failure for each group were as follows: Group I (n=432): 31 (7.17%); Group II (n=387): 11.11%; Group III (n=317): 90 (28.50%) (F=54.3, P<0.001). After performing 1:1 propensity score matching for the different groups, 223 pairs were obtained. Analysis using the Cox proportional hazards model showed that compared to Group I, the risk of readmission for Group II was 1.372 (95% CI: 1.125-1.682, P<0.001), and for Group III was 2.053 (95% CI: 1.006-5.437, P<0.001). Furthermore, binary logistic regression analysis, including variables such as digoxin, hypertension, smoking, coronary heart disease, and chronic obstructive pulmonary disease as independent variables, revealed that coronary heart disease and COPD also had a significant impact on readmission due to heart failure (p<0.001). Conclusion: The correlation between the heart rate control level of patients with persistent atrial fibrillation and the risk of heart failure rehospitalization is positive. Reasonable heart rate control may significantly reduce the risk of heart failure rehospitalization.

Keywords: heart rate control levels, heart failure rehospitalization, persistent atrial fibrillation, retrospective cohort study

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

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Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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Authors: Rahy Farooq, Maria Ahmad Khan, Ayesha Isani Majeed

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Objective: The main aim of this research is to assess the knowledge, attitude and practices of female nursing staff and nursing students regarding breast cancer, to provide a baseline for monitoring trends of breast cancer awareness in them. Background: Healthcare professionals are a direct source of information for the patients and the general public as a whole. It is, therefore, essential that the information they convey be accurate and helps in building additional awareness. However, clinical experience does not influence the knowledge, attitude and practices regarding breast cancer. Nurses, being the prime part of the healthcare professionals, play a significant role and hence, their awareness regarding this pressing issue is pertinent. Lack of awareness regarding common presenting symptoms or breast cancer risk factors translates to poor breast cancer screening practices and late diagnosis. Methodology: A cross-sectional study of 280 female nurses was conducted at a tertiary care hospital in Islamabad, Pakistan. A pre-tested structured questionnaire with additional variables like cultural barriers to seeking medical help was used. The scores for outcome variables including knowledge, attitude and practices were pre-defined. Data was analyzed using SPSSv23. Results: Of the 280 participants with a mean age of 28.99±9.98 years, 142 (50.7%) were married, and 138 (49.3%) were unmarried. Mean scores were computed to be 6.14±2.93 (out of 12), 0.30±0.7 (out of 3) and 9.53±1.92 (out of 16) for knowledge, attitude and practice respectively. Using independent sample T-test, a statistically significant correlation was found when means for the score of Attitude was compared with age. With a p-value of 0.018, 117 nurses of age more than 30 years, faced more practical, financial, emotional and service barriers as compared to 163 women younger than 30 years of age. Knowledge of age-related lifetime risks was also significantly poor more in single women; with a p-value of 0.006 for identification of correct age as a risk factor and a p-value of 0.005 for correct identification of risk for development of breast cancer in the lifetime of women. By application of Chi-square test, there was a significant correlation between marital status and cultural barriers to seeking medical help, showing that single women (58.7%) shy away from talking about breast cancer considering it a taboo (p-value 0.028) whereas, more married nurses (59.2%) were apprehensive that they might be considered at fault by the society, as compared to 40.8% of single nurses. (p-value 0.038). Conclusion: Owing to the scarcity of awareness among nurses, this study recognizes the need for delivering effective information to the female nurses regarding breast cancer. Educating patients is likely to be effective if the female nurses play their part and have correct attitudes towards breast cancer practices. A better understanding of the knowledge and practices regarding breast cancer among the nursing population will enable high-risk patients to be recognized early. Therefore, we recommend arrangement of special courses and seminars for all healthcare professionals including the nursing staff.

Keywords: breast cancer, cultural barriers, kap, nurses

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Authors: Amit Bhunia, Mohit Kumar Singh, Maryam Al Huwayz, Mohamed Henini, Shouvik Datta

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We report [https://arxiv.org/abs/2107.13518] experimental detection and control of Schrodinger’s Cat like macroscopically large, quantum coherent state of a two-component Bose-Einstein condensate of spatially indirect electron-hole pairs or excitons using a resonant tunneling diode of III-V Semiconductors. This provides access to millions of excitons as qubits to allow efficient, fault-tolerant quantum computation. In this work, we measure phase-coherent periodic oscillations in photo-generated capacitance as a function of an applied voltage bias and light intensity over a macroscopically large area. Periodic presence and absence of splitting of excitonic peaks in the optical spectra measured by photocapacitance point towards tunneling induced variations in capacitive coupling between the quantum well and quantum dots. Observation of negative ‘quantum capacitance’ due to a screening of charge carriers by the quantum well indicates Coulomb correlations of interacting excitons in the plane of the sample. We also establish that coherent resonant tunneling in this well-dot heterostructure restricts the available momentum space of the charge carriers within this quantum well. Consequently, the electric polarization vector of the associated indirect excitons collective orients along the direction of applied bias and these excitons undergo Bose-Einstein condensation below ~100 K. Generation of interference beats in photocapacitance oscillation even with incoherent white light further confirm the presence of stable, long-range spatial correlation among these indirect excitons. We finally demonstrate collective Rabi oscillations of these macroscopically large, ‘multipartite’, two-level, coupled and uncoupled quantum states of excitonic condensate as qubits. Therefore, our study not only brings the physics and technology of Bose-Einstein condensation within the reaches of semiconductor chips but also opens up experimental investigations of the fundamentals of quantum physics using similar techniques. Operational temperatures of such two-component excitonic BEC can be raised further with a more densely packed, ordered array of QDs and/or using materials having larger excitonic binding energies. However, fabrications of single crystals of 0D-2D heterostructures using 2D materials (e.g. transition metal di-chalcogenides, oxides, perovskites etc.) having higher excitonic binding energies are still an open challenge for semiconductor optoelectronics. As of now, these 0D-2D heterostructures can already be scaled up for mass production of miniaturized, portable quantum optoelectronic devices using the existing III-V and/or Nitride based semiconductor fabrication technologies.

Keywords: exciton, Bose-Einstein condensation, quantum computation, heterostructures, semiconductor Physics, quantum fluids, Schrodinger's Cat

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Authors: Parminder Kaur Heer, Alexei Lapkin

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Due to global challenges of increased competition and demand for more sustainable products/processes, there is a rising pressure on the industry to develop innovative processes. Through Process Intensification (PI) the existing and new processes may be able to attain higher efficiency. However, very few PI options are generally considered. This is because processes are typically analysed at a unit operation level, thus limiting the search space for potential process options. PI performed at more detailed levels of a process can increase the size of the search space. The different levels at which PI can be achieved is unit operations, functional and phenomena level. Physical/chemical phenomena form the lowest level of aggregation and thus, are expected to give the highest impact because all the intensification options can be described by their enhancement. The objective of the current work is thus, generation of numerous process alternatives based on phenomena, and development of their corresponding computer aided models. The methodology comprises: a) automated generation of process options, and b) automated generation of process models. The process under investigation is disintegrated into functions viz. reaction, separation etc., and these functions are further broken down into the phenomena required to perform them. E.g., separation may be performed via vapour-liquid or liquid-liquid equilibrium. A list of phenomena for the process is formed and new phenomena, which can overcome the difficulties/drawbacks of the current process or can enhance the effectiveness of the process, are added to the list. For instance, catalyst separation issue can be handled by using solid catalysts; the corresponding phenomena are identified and added. The phenomena are then combined to generate all possible combinations. However, not all combinations make sense and, hence, screening is carried out to discard the combinations that are meaningless. For example, phase change phenomena need the co-presence of the energy transfer phenomena. Feasible combinations of phenomena are then assigned to the functions they execute. A combination may accomplish a single or multiple functions, i.e. it might perform reaction or reaction with separation. The combinations are then allotted to the functions needed for the process. This creates a series of options for carrying out each function. Combination of these options for different functions in the process leads to the generation of superstructure of process options. These process options, which are formed by a list of phenomena for each function, are passed to the model generation algorithm in the form of binaries (1, 0). The algorithm gathers the active phenomena and couples them to generate the model. A series of models is generated for the functions, which are combined to get the process model. The most promising process options are then chosen subjected to a performance criterion, for example purity of product, or via a multi-objective Pareto optimisation. The methodology was applied to a two-step process and the best route was determined based on the higher product yield. The current methodology can identify, produce and evaluate process intensification options from which the optimal process can be determined. It can be applied to any chemical/biochemical process because of its generic nature.

Keywords: Phenomena, Process intensification, Process models , Process options

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Authors: Kathryn McMillan

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A recent study of 8500 adult Australians aged 16 and over revealed 62% had experienced childhood maltreatment. In response to multiple recommendations by bodies such as the Australian Law Reform Commission, parliamentary reports and stakeholder input, a number of key initiatives have been developed to grapple with the difficulties of a federal-state system and to screen and triage high-risk families navigating their way through the court system. The Lighthouse Project (LHP) is a world-first initiative of the Federal Circuit and Family Courts in Australia (FCFOCA) to screen family law litigants for major risk factors, including family violence, child abuse, alcohol or substance abuse and mental ill-health at the point of filing in all applications that seek parenting orders. It commenced on 7 December 2020 on a pilot basis but has now been expanded to 15 registries across the country. A specialist risk screen, Family DOORS, Triage has been developed – focused on improving the safety and wellbeing of families involved in the family law system safety planning and service referral, and ¬ differentiated case management based on risk level, with the Evatt List specifically designed to manage the highest risk cases. Early signs are that this approach is meeting the needs of families with multiple risks moving through the Court system. Before the LHP, there was no data available about the prevalence of risk factors experienced by litigants entering the family courts and it was often assumed that it was the litigation process that was fueling family violence and other risks such as suicidality. Data from the 2022 FCFCOA annual report indicated that in parenting proceedings, 70% alleged a child had been or was at risk of abuse, 80% alleged a party had experienced Family Violence, 74 % of children had been exposed to Family Violence, 53% alleged through substance misuse by party children had caused or was at risk of causing harm to children and 58% of matters allege mental health issues of a party had caused or placed a child at risk of harm. Those figures reveal the significant overlap between child protection and family violence, both of which are under the responsibility of state and territory governments. Since 2020, a further key initiative has been the co-location of child protection and police officials amongst a number of registries of the FCFOCA. The ability to access in a time-effective way details of family violence or child protection orders, weapons licenses, criminal convictions or proceedings is key to managing issues across the state and federal divide. It ensures a more cohesive and effective response to family law, family violence and child protection systems.

Keywords: child protection, family violence, parenting, risk screening, triage.

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Meryam Labyad, Karima Fakiri, Widad Lahmini, Ghizlane Draiss, Mohamed Bouskraoui, Nadia Ouzennou

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Background: Asthma is the most common chronic disease in children, affecting nearly 235 million people worldwide (OMS). In Morocco, asthma is much more common in children than in adults; the prevalence rate in children between 13 and 14 years of age is 20%.1 This pathology is marked by high morbidity, a significant impact on the quality of life and development of children 2 This requires a rigorous management strategy in order to achieve clinical control and reduce any risk to the patient 3 A search for aggravating factors is mandatory if a child has difficulty maintaining good asthma control. The objective of the present study is to describe asthma control during this confinement period in children aged 4 to 11 years followed by a pneumo-paediatric consultation. For children whose asthma is not controlled, a search for associations with promoting factors and adherence to treatment is also among the objectives of the study. Knowing the level of asthma control and influencing factors is a therapeutic priority in order to reduce hospitalizations and emergency care use. Objective: To assess asthma control and determine the factors influencing asthma levels in children with asthma during confinement following the COVID 19 pandemic. Method: Prospective cross-sectional study by questionnaire and structured interview among 66 asthmatic children followed in pediatric pneumology consultation at the CHU MED VI of Marrakech from 13/06/2020 to 13/07/2020, asthma control was assessed by the Childhood Asthma Control Test (C-ACT). Results: 66 children and their parents were included (mean age is 7.5 years), asthma was associated with allergic rhinitis (13.5% of cases), conjunctivitis (9% of cases), eczema (12% of cases), occurrence of infection (10.5% of cases). The period of confinement was marked by a decrease in the number of asthma attacks translated by a decrease in the number of emergency room visits (7.5%) of these asthmatic children, control was well controlled in 71% of the children, this control was significantly associated with good adherence to treatment (p<0.001), no infection (p<0.001) and no conjunctivitis (p=002) or rhinitis (p<0.001). This improvement in asthma control during confinement can be explained by the measures taken in the Kingdom to prevent the spread of COVID 19 (school closures, reduction in industrial activity, fewer means of transport, etc.), leading to a decrease in children's exposure to triggers, which justifies the decrease in the number of children having had an infection, allergic rhinitis or conjunctivitis during this period. In addition, the close monitoring of parents resulted in better therapeutic adherence (42.4% were fully observant). Confinement was positively perceived by 68% of the parents; this perception is significantly associated with the level of asthma control (p<0.001). Conclusion: Maintaining good control can be achieved through improved therapeutic adherence and avoidance of triggers, both of which were achieved during the containment period following the VIDOC pandemic 19.

Keywords: Asthma, control , COVID-19 , children

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Authors: José Maria, Vânia Laranjo, Luís Abrunhosa, António Inês

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The occurrence of mycotoxigenic moulds such as Aspergillus, Penicillium and Fusarium in food and feed has an important impact on public health, by the appearance of acute and chronic mycotoxicoses in humans and animals, which is more severe in the developing countries due to lack of food security, poverty and malnutrition. This mould contamination also constitutes a major economic problem due the lost of crop production. A great variety of filamentous fungi is able to produce highly toxic secondary metabolites known as mycotoxins. Most of the mycotoxins are carcinogenic, mutagenic, neurotoxic and immunosuppressive, being ochratoxin A (OTA) one of the most important. OTA is toxic to animals and humans, mainly due to its nephrotoxic properties. Several approaches have been developed for decontamination of mycotoxins in foods, such as, prevention of contamination, biodegradation of mycotoxins-containing food and feed with microorganisms or enzymes and inhibition or absorption of mycotoxin content of consumed food into the digestive tract. Some group of Gram-positive bacteria named lactic acid bacteria (LAB) are able to release some molecules that can influence the mould growth, improving the shelf life of many fermented products and reducing health risks due to exposure to mycotoxins. Some LAB are capable of mycotoxin detoxification. Recently our group was the first to describe the ability of LAB strains to biodegrade OTA, more specifically, Pediococcus parvulus strains isolated from Douro wines. The pathway of this biodegradation was identified previously in other microorganisms. OTA can be degraded through the hydrolysis of the amide bond that links the L-β-phenylalanine molecule to the ochratoxin alpha (OTα) a non toxic compound. It is known that some peptidases from different origins can mediate the hydrolysis reaction like, carboxypeptidase A an enzyme from the bovine pancreas, a commercial lipase and several commercial proteases. So, we wanted to have a better understanding of this OTA degradation process when LAB are involved and identify which molecules where present in this process. For achieving our aim we used some bioinformatics tools (BLAST, CLUSTALX2, CLC Sequence Viewer 7, Finch TV). We also designed specific primers and realized gene specific PCR. The template DNA used came from LAB strains samples of our previous work, and other DNA LAB strains isolated from elderberry fruit, silage, milk and sausages. Through the employment of bioinformatics tools it was possible to identify several proteins belonging to the carboxypeptidase family that participate in the process of OTA degradation, such as serine type D-Ala-D-Ala carboxypeptidase and membrane carboxypeptidase. In conclusions, this work has identified carboxypeptidase proteins being one of the molecules present in the OTA degradation process when LAB are involved.

Keywords: carboxypeptidase, lactic acid bacteria, mycotoxins, ochratoxin a.

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Authors: Pariya Sheykhmaleki, Debajyoti Pati

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Rural areas in the United States face numerous challenges in providing quality and assessable primary healthcare services, especially during emergencies such as natural disasters or pandemics. This study showcases a cutting-edge flexible module that aims to overcome these challenges by offering adaptable healthcare facilities capable of providing comprehensive health services in remote and disaster-prone regions. According to the Health Resources and Services Administration (HRSA), approximately 62 million Americans, or 1 in 5 individuals, live in areas designated as Health Professional Shortage Areas (HPSAs) for primary care. These areas are characterized by limited access to healthcare facilities, shortage of healthcare professionals, transportation barriers, inadequate healthcare infrastructure, higher rates of chronic diseases, mental health disparities, and limited availability of specialized care, including urgent circumstances like pandemics that can exacerbate this issue. To address these challenges, the literature study began by examining primary health solutions in very remote areas, e.g., spaceships, to identify the state-of-the-art technologies and the methods used to facilitate primary care needs. The literature study on flexibility in architecture and interior design was also adapted to develop a conceptual design for rural areas. The designed flexible module provides an innovative solution. This module can be prefabricated as all parts are standardized. The flexibility of the module allows the structure to be modified based on local and geographical requirements as well as the ability to expand as required. It has been designed to stand either by itself or work in tandem with public buildings. By utilizing sustainable approaches and flexible spatial configurations, the module optimizes the utilization of limited resources while ensuring efficient and effective healthcare delivery. Furthermore, the poster highlights the key features of this flexible module, including its ability to support telemedicine and telehealth services for all five levels of urgent care conditions, i.e., from facilitating fast tracks to supporting emergency room services, in two divided zones. The module's versatility enables its deployment in rural areas located far from urban centers and disaster-stricken regions, ensuring access to critical healthcare services in times of need. This module is also capable of responding in urban areas when the need for primary health becomes vastly urgent, e.g., during a pandemic. It emphasizes the module's potential to bridge the healthcare gap between rural and urban areas and mitigate the impact of rural health challenges.

Keywords: rural health, healthcare challenges, flexible modular design, telemedicine, telehealth

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Authors: Diana Vieira Figueiredo, Rita Ramos Miguel, Maria do Céu Salvador, Luiza Nobre-Lima, Daniel RIjo, Paula Vagos

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Social Anxiety Disorder (SAD) is characterized by a marked and persistent fear of social and/or performance situations in which one may be exposed to the scrutiny of others.  SAD has its usual onset and is highly prevalent during adolescence; if left untreated, it often has a chronic and unremitting course. So, it seems important to understand the psychological processes that might predict the development of SAD. One of these processes may be self-compassion, which has been found to be associated with social anxiety in both adults and adolescents. Self-compassion involves three main components, each with a positive (compassionate behavior) and negative (uncompassionate behavior) pole – self-kindness versus self-judgment, common humanity versus isolation, and mindfulness versus over-identification. The negative indicators of self-compassion (self-judgement, isolation, and over-identification) were found to be more strongly linked to mental health problems than the positive indicators (self-kindness, common humanity, and mindfulness). Additionally, negative associations were found between the positive indicators of self-compassion (self-kindness, common humanity, mindfulness) and psychopathology. The current study aimed to investigate the role of self-kindness, self-judgment, common humanity, isolation, mindfulness, and over-identification in the likelihood of an adolescent presenting SAD by comparing groups of normative and socially anxious adolescents. The sample consisted of 32 adolescents (Mage = 15.88, SD = .833) of which 23 were girls. Adolescents were assessed through a clinical structured interview that led 17 to be assigned to the clinical group (presenting a primary diagnosis of SAD) and 15 to be assigned to the non-clinical group (presenting no clinical diagnosis). Variables under study were measured through the Self-Compassion Scale for adolescents (SCS-A), which assesses the six indicators of self-compassion presented above. Six separate models were tested, each with one of the subscales of the SCS-A as the independent variable and with the group (clinical versus non-clinical) as the dependent variable. The models considering isolation, over-identification, self-judgement, and self-kindness fitted the data and accurately predicted group belonging for between 75% to 84.4% of cases. Results indicated that the log of the odds of an adolescent presenting SAD was positively related to isolation, over-identification, and self-judgement and negatively associated with self-kindness. Findings provide support for the idea that decreased self-compassion may place adolescents at increased risk for experiencing clinical levels of social anxiety: on the one hand, adolescents with higher levels of isolation, over-identification, and self-judgement seem to be more prone to the development of psychopathological levels of social anxiety; on the other hand, self-kindness may play a protective role in the development of SAD in this developmental phase. So, if focusing on social feared consequences and perceiving to be different from others may be distinctive features of SAD, developing self-kindness may be the antidote to promote diminished levels of social anxiety and more.

Keywords: adolescents, social anxiety disorder, self-compassion, diagnosis odds-ration

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Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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Authors: Abdirahman Barre, Abdihamid Salad Hassan, Iftin Abdi Mohamud, Abdirahman Mohamed Mohamud, Ahmed Adan Mohamed, Mukhtaar Mohamed Idow

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Pasteurellosis (Hemorrhagic septicemia) is a common respiratory disease of camel that is an acutely fatal disease caused by Pasteurella multocida type A or several serotypes of Mannheimia hemolytic, which also affect other animals. The disease had shown to spread between animals, across herds and to humans. Meaning that the disease is Zoonosis. The study aimed at establishment of sero-prevalence of Pasteurellosis in some selected Districts of camel rearing in the Benadir Region. It was a cross-sectional study, where the study population was purposively chosen to consist of animals taken within three sub-Districts of Benadir Region, namely Sub-District (Daynile Township), Sub-District (Yaaqshid) Sub-District (kaxda). This was because they normally handle many camels in a day, thus making it easy for the investigator to access the required number conveniently; it was also assumed that data collected from these for-slaughter camels was representative of the situation in the sub-District/county. A total of one hundred and sixty camels were tested using four serological tests: Rose Bengal Plate Test (RBPT),) and Complex Fixation Test (CFT). The serological tests were purposively chosen to increase the chances of picking positive cases and also to compare their sensitivities with respect to camel serum since they were originally meant for use on bovine serum. Blood samples (15 ml) were collected for serum harvesting from the jugular veins of the animals as they were waiting to be examined. Rose Bengal plate test and CFT were run at a laboratory within the Department of Veterinary Medicine, University of Horsed, 21 October campus; serum samples having been transported in a cool box. On average, out of an overall total of 300 serum samples tested, 180 samples were selected as sample procedures and were given eleven (11) positive results, amounting to a prevalence of 6.67%. For the three Districts, respective prevalence (averaged from the two (2) serological tests run) were: 7% (3/50) for Yaqshiid; 8% (3/60) for Deyniile and 10% (3/70) for Kaxda. When sensitivities of the two (2) serological tests were compared, there was no significant difference between them with respect to the picking of positive cases (p=0.05). The study has demonstrated presence of Pasterolosis in camels in Benadir Region and the authors are recommending the usage of RBPT and CFT as screening tests, since they are cheap, quick, and easy to carry out. Any of the other three involving tests can then be used if one wants to establish respective titers. Therefore, further detailed investigation needs to be conducted so as to understand specific etiological agents causing pasteurollosis in camel and can be instituted to optimize the benefit obtained from the camel sector.

Keywords: hemorrhagic septicemia, camel, prevalence, Benadir region, Somalia

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Authors: Liliana Gomez Cardona, Echo Parent-Racine, Joy Outerbridge, Arlene Laliberté, Outi Linnaranta

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Suicide rates among Inuit in Nunavik are six to eleven times larger than the Canadian average. The colonization, religious missions, residential schools as well as economic and political marginalization are factors that have challenged the well-being and mental health of these populations. In psychiatry, screening for mental illness is often done using questionnaires with which the patient is expected to respond how often he/she has certain symptoms. However, the Indigenous view of mental wellbeing may not fit well with this approach. Moreover, biomedical treatments do not always meet the needs of Indigenous peoples because they do not understand the culture and traditional healing methods that persist in many communities. Assess whether the questionnaires used to measure symptoms, commonly used in psychiatry are appropriate and culturally safe for the Inuit in Quebec. Identify the most appropriate tool to assess and promote wellbeing and follow the process necessary to improve its cultural sensitivity and safety for the Inuit population. Qualitative, collaborative, and participatory action research project which respects First Nations and Inuit protocols and the principles of ownership, control, access, and possession (OCAP). Data collection based on five focus groups with stakeholders working with these populations and members of Indigenous communities. Thematic analysis of the data collected and emerging through an advisory group that led a revision of the content, use, and cultural and conceptual relevance of the instruments. The questionnaires measuring psychiatric symptoms face significant limitations in the local indigenous context. We present the factors that make these tools not relevant among Inuit. Although the scale called Growth and Empowerment Measure (GEM) was originally developed among Indigenous in Australia, the Inuit in Quebec found that this tool comprehends critical aspects of their mental health and wellbeing more respectfully and accurately than questionnaires focused on measuring symptoms. We document the process of cultural adaptation of this tool which was supported by community members to create a culturally safe tool that helps in resilience and empowerment. The cultural adaptation of the GEM provides valuable information about the factors affecting wellbeing and contributes to mental health promotion. This process improves mental health services by giving health care providers useful information about the Inuit population and their clients. We believe that integrating this tool in interventions can help create a bridge to improve communication between the Indigenous cultural perspective of the patient and the biomedical view of health care providers. Further work is needed to confirm the clinical utility of this tool in psychological and psychiatric intervention along with social and community services.

Keywords: cultural adaptation, cultural safety, empowerment, Inuit, mental health, Nunavik, resiliency

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Authors: P. Tardi, B. Szilagyi, A. Makai, P. Acs, M. Hock, M. Jaromi

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Osteoporosis is becoming a major public health problem, particularly in postmenopausal women, as the incidence of this disease is getting higher. Nowadays, one of the most common chronic musculoskeletal diseases is osteoporosis. Osteoporosis-related knowledge is an important contributor to prevent or to treat osteoporosis. The most important strategies to prevent or treat the disease are increasing the level of physical activity at all ages, cessation of smoking, reduction of alcohol consumption, adequate dietary calcium, and vitamin D intake. The aim of the study was to measure the osteoporosis-related knowledge and physical activity among women age over 50 years. For the measurements, we used the osteoporosis questionnaire (OPQ) to examine the disease-specific knowledge and the global physical activity questionnaire (GPAQ) to measure the quantity and quality of the physical activity. The OPQ is a self-administered 20-item questionnaire with five categories: general information, risk factors, investigations, consequences, and treatment. There are four choices per question (one of them is the 'I do not know'). The filler gets +1 for a good answer, -1 point for a bad answer, and 0 for 'I do not know' answer. We contacted with 326 women (63.08 ± 9.36 year) to fill out the questionnaires. Descriptive analysis was carried out, and we calculated Spearman's correlation coefficient to examine the relationship between the variables. Data were entered into Microsoft Excel, and all statistical analyses were performed using SPSS (Version 24). The participants of the study (n=326) reached 8.76 ± 6.94 points on OPQ. Significant (p < 0.001) differences were found in the results of OPQ according to the highest level of education. It was observed that the score of the participants with osteoporosis (10.07 ± 6.82 points) was significantly (p=0.003) higher than participants without osteoporosis (9.38 ± 6.66 points) and the score of those women (6.49 ± 6.97 points) who did not know that osteoporosis exists in their case. The GPAQ results showed the sample physical activity in the dimensions of vigorous work (479.86 ± 684.02 min/week); moderate work (678.16 ± 804.5 min/week); travel (262.83 ± 380.27 min/week); vigorous recreation (77.71 ± 123.46 min/week); moderate recreation (115.15 ± 154.82 min/week) and total weekly physical activity (1645.99 ± 1432.88 min/week). Significant correlations were found between the osteoporosis-related knowledge and the physical activity in travel (R=0.21; p < 0.001), vigorous recreation (R=0.35; p < 0.001), moderate recreation (R=0.35; p < 0.001), total vigorous minutes/week (R=0.15; p=0.001) and total moderate minutes/week (R=0.13; p=0.04) dimensions. According to the results that were achieved, the highest level of education significantly determines osteoporosis-related knowledge. Physical activity is an important contributor to prevent or to treat osteoporosis, and it showed a significant correlation with osteoporosis-related knowledge. Based on the results, the development of osteoporosis-related knowledge may help to improve the level of physical activity, especially recreation. Acknowledgment: Supported by the ÚNKP-20-1 New National Excellence Program of The Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation Fund.

Keywords: osteoporosis, osteoporosis-related knowledge, physical activity, prevention

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Authors: Narayana Bhat, Majda Khalil, Hamad Al-Mansour, Anitha Manuvel, Vimla Yeddu

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The aim of this study was to assess the antimicrobial and antioxidant potential and phytochemical composition of Peganum harmala L. For this purpose, powdered shoot, root, and seed samples were extracted in an accelerated solvent extractor (ASE) with methanol, ethanol, acetone, and dichloromethane. The residues were reconstituted in the above solvents and 10% dimethyl sulphoxide (DMSO). The antimicrobial activity of these extracts was tested against two bacterial (Escherichia coli E49 and Staphylococcus aureus CCUG 43507) and two fungi Candida albicans ATCC 24433, Candida glabrata ATCC 15545) strains using the well-diffusion method. The minimum inhibitory concentration (MIC) and growth pattern of these test strains were determined using microbroth dilution method, and the phospholipase assay was performed to detect tissue damage in the host cells. Results revealed that ethanolic, methanolic, and dichloromethane extracts of seeds exhibited significant antimicrobial activities against all tested strains, whereas the acetone extract of seeds was effective against E. coli only. Similarly, ethanolic and methanolic extracts of roots were effective against two bacterial strains only. One sixth of percent (0.6%) yield of methanol extract of seeds was found to be the MIC for Escherichia coli E49, Staphylococcus aureus CCUG 43507, and Candida glabrata ATCC 15545. Overall, seed extracts had greater antimicrobial activities compared to roots and shoot extracts. The original plant extract and MIC dilutions prevented phospholipase secretion in Staphylococcus aureus CCUG 43507 and Candida albicans ATCC 24433. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay revealed radical scavenging activities ranging from 71.80 ± 4.36% to 87.75 ± 1.70%. The main compound present in the root extract was 1-methyl-7-methoxy-beta-carboline (RT: 44.171), followed by norlapachol (3.62%), benzopyrazine (2.20%), palmitic acid (2.12%) and vasicinone (1.96%). In contrast, phenol,4-ethenyl-2-methoxy was in abundance in the methonolic extract of the shoot, whereas 1-methyl-7-methoxy-beta-carboline (79.59%), linoleic acid (9.05%), delta-tocopherol (5.02%), 9,12-octadecadienoic acid, methyl ester (2.65%), benzene, 1,1-1,2 ethanediyl bis 3,4dimethyl (1.15%), anthraquinone (0.58%), hexadecanoic acid, methyl ester (0.54%), palmitic acid (0.35%) and methyl stearate (0.18%) were present in the methanol extract of seeds. Major findings of this study, along with their relevance to developing effective, safe drugs, will be discussed in this presentation.

Keywords: medicinal plants, secondary metabolites, phytochemical screening, bioprospecting, radical scavenging

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Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr

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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.

Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin

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Authors: Jacqueline P. Davies

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Introduction: Student nurses must develop skills in observation, communication and reflection as well as public health knowledge from their first year of training. This paper will explain a method developed for students to collect their own findings about public health in urban areas. These areas are both rich in the history of old public health that informs the content of many traditional public health walks, but are also locations where new public health concerns about chronic disease are concentrated. The learning method explained in this paper enables students to collect their own data and write original work as first year students. Examples of their findings will be given. Methodology: In small groups, health care students are instructed to walk in neighbourhoods near to the hospitals they will soon attend as apprentice nurses. On their walks, they wander slowly, engage in conversations, and enter places open to the public. As they drift, they observe with all five senses in the real three dimensional world to collect data for their reflective accounts of old and new public health. They are encouraged to stop for refreshments and taste, as well as look, hear, smell, and touch while on their walk. They reflect as a group and later develop an individual reflective account in which they write up their deep reflections about what they observed on their walk. In preparation for their walk, they are encouraged to look at studies of quality of Life and other neighbourhood statistics as well as undertaking a risk assessment for their walk. Findings: Reflecting on their walks, students apply theoretical concepts around social determinants of health and health inequalities to develop their understanding of communities in the neighbourhoods visited. They write about the treasured historical architecture made of stone, bronze and marble which have outlived those who built them; but also how the streets are used now. The students develop their observations into thematic analyses such as: what we drink as illustrated by the empty coke can tossed into a now disused drinking fountain; the shift in home-life balance illustrated by streets where families once lived over the shop which are now walked by commuters weaving around each other as they talk on their mobile phones; and security on the street, with CCTV cameras placed at regular intervals, signs warning trespasses and barbed wire; but little evidence of local people watching the street. Conclusion: In evaluations of their first year, students have reported the health walk as one of their best experiences. The innovative approach was commended by the UK governing body of nurse education and it received a quality award from the nurse education funding body. This approach to education allows students to develop skills in the real world and write original work.

Keywords: education, innovation, nursing, urban

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Nada Verdel, Tomaz Rijavec, Albin Pintar, Ales Lapanje

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Objectives: White water circuits of woodfree paper mills contain suspended, dissolved, and colloidal particles, such as cellulose, starch, paper sizings, and dyes. By closing the white water circuits, these particles start to accumulate and affect the production. Due to high amount of organic matter that scavenge radicals and adsorbs onto catalyst surfaces, treatment of white water with photocatalysis is inappropriate. The most suitable approach should be bioaugmentation-assisted bioremediation. Accordingly, objectives were: - to isolate bacteria capable of degrading organic compounds used for the papermaking process - to select the most active bacteria for bioaugmentation. Status: The state-of-the-art of bioaugmentation of pulp and paper mill effluents is mostly based on biodegradation of lignin. Whereas in white water circuits of woodfree paper mills only papermaking compounds are present. As far as one can tell from the literature, the study on degradation activities of bacteria for all possible compounds of the papermaking process is a novelty. Methodology: The main parameters of the selected white water were systematically analyzed during a period of two months. Bacteria were isolated on selective media with particular carbon source. Organic substances used as carbon source either enter white water circuits as base paper or as recycled broke. The screening of bacterial activities for starch, cellulose, latex, polyvinyl alcohol, alkyl ketene dimers, and resin acids was followed by addition of lugol. Degraders of polycyclic aromatic dyes were selected by cometabolism tests; cometabolism is simultaneous biodegradation of two compounds, in which the degradation of the second compound depends on the presence of the first. The obtained strains were identified by 16S rRNA sequencing. Findings: 335 autochthonous strains were isolated on plates with selected carbon source. The isolated strains were selected according to degradation of the particular carbon source. The ultimate degraders of cationic starch, cellulose, and sizings are Pseudomonas sp. NV-CE12-CF and Aeromonas sp. NV-RES19-BTP. The most active strains capable of degrading azo dyes are Aeromonas sp. NV-RES19-BTP and Sphingomonas sp. NV-B14-CF. Klebsiella sp. NV-Y14A-BTP degrade polycyclic aromatic direct blue 15 and also yellow dye, Agromyces sp. NV-RED15A-BF and Cellulosimicrobium sp. NV-A4-BF are specialists for whitener and Aeromonas sp. NV-RES19-BTP is general degrader of all compounds. To the white water adapted bacteria were isolated and selected according to their degradation activities for particular organic substances. Mostly isolated bacteria are specialized to lower the competition in the microbial community. Degraders of readily-biodegradable compounds do not degrade recalcitrant polycyclic aromatic dyes and vice versa. General degraders are rare.

Keywords: bioaugmentation, biodegradation of azo dyes, cometabolism, smart wastewater treatment technologies

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Authors: Matt Fullmer, Carol Wilkinson, Keven Prusak, Dennis Eggett, Todd Pennington

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Obesity and chronic health issues are linked to physical inactivity. Physical education (PE) programs in school can play a major role in combating these health-related issues. This study focused on supporting competence through keeping a leisure-time physical activity (LTPA) record as part of PE. Keeping a daily LTPA record may be an effective intervention helping students feel more competent toward exercise, and thus, self-determined (within the context of self-determination theory) to exercise. Little is known about the relationship between daily LTPA records and perceived competence, motivational profiles, and LTPA levels of students enrolled in PE. This study examined the relationship between keeping a daily, online LTPA record and adolescent (a) motivational profiles toward LTPA, (b) perceived competence toward LTPA, and (c) LTPA behaviors. Secondary students (N = 124) in physical education classes completed a baseline questionnaire which consisted of the Behavioural Regulation in Exercise Questionnaire–2, the Perceived Competence Scale, and the Godin Leisure-Time Exercise Questionnaire. For three weeks, the students were assigned to keep the Presidential Active Lifestyle Award Challenge (PALAC) as their online LTPA record. They completed the questionnaire after each week. A 2 (gender) x 4 (trials) repeated measures ANCOVA examined the relationships between recording compliance and motivation, perceived competence, and physical activity. Results showed that recording compliance was not a significant predictor of perceived competence to participate in LTPA. Examining motivational factors, a significant interaction between recording compliance and introjected regulation was found. The more students recorded the less motivated they were by guilt or obligation to exercise in their leisure-time. Also, a significant interaction was found between recording compliance and intrinsic regulation, indicating that the more students recorded the more intrinsically motivated they were to exercise in their leisure-time. Lastly, there was a significant interaction between recording compliance and LTPA. As students kept the LTPA record, girls’ LTPA levels significantly decreased and boys’ LTPA levels significantly increased. The key findings are that, as implemented in this study: a) the lack of PALAC compliance suggests that daily LTPA records may NOT be the most effective intervention for this population, b) keeping a daily LTPA record did NOT help students feel more competent to exercise in their leisure-time, c) a daily LTPA record may help students move towards being more self-determined in their feelings towards LTPA, and d) the outcome of keeping a LTPA record on LTPA behavior is statistically significant, although actual differences may not be practically important.

Keywords: behavioural regulation in exercise questionnaire–2, Godin leisure–time exercise questionnaire, online physical activity log, perceived competence scale, self-determination theory

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Authors: Hafsa Kamran, Asma Afreen, Zaheer Ahmed

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Internet addiction, an emerging mental health disorder from last two decades, is manifested by the inability in the controlled use of internet leading to academics, social, physiological and/or psychological difficulties. The present study aimed to assess the levels of internet addiction among university students in Lahore and to explore the effects of internet addiction on their dietary behavior and lifestyle. It was an analytical cross-sectional study. Data was collected from October to December 2016 from students of four universities selected through two-stage sampling method. The numbers of participants were 500 and 13 questionnaires were rejected due to incomplete information. Levels of Internet Addiction (IA) were calculated using Young Internet Addiction Test (YIAT). Data was also collected on students’ demographics, lifestyle factors and dietary behavior using self-reported questionnaire. Data was analyzed using SPSS (version 21). Chi-square test was applied to evaluate the relationship between variables. Results of the study revealed that 10% of the population had severe internet addiction while moderate Internet Addiction was present in 42%. High prevalence was found among males (11% vs. 8%), private sector university students (p = 0.008) and engineering students (p = 0.000). The lifestyle habits of internet addicts were significantly of poorer quality than normal users (p = 0.05). Internet addiction was found associated with lesser physically activity (p = 0.025), had shorter duration of physical activity (p = 0.016), had more disorganized sleep pattern (p = 0.023), had less duration of sleep (p = 0.019), reported being more tired and sleepy in class (p = 0.033) and spending more time on internet as compared to normal users. Severe and moderate internet addicts also found to be more overweight and obese than normal users (p = 0.000). The dietary behavior of internet addicts was significantly poorer than normal users. Internet addicts were found to skip breakfast more than a normal user (p = 0.039). Common reasons for meal skipping were lack of time and snacking between meals (p = 0.000). They also had increased meal size (p = 0.05) and habit of snacking while using the internet (p = 0.027). Fast food (p = 0.016) and fried items (p = 0.05) were most consumed snacks, while carbonated beverages (p = 0.019) were most consumed beverages among internet addicts. Internet Addicts were found to consume less than recommended daily servings of dairy (p = 0.008) and fruits (p = 0.000) and more servings of meat group (p = 0.025) than their no internet addict counterparts. In conclusion, in this study, it was demonstrated that internet addicts have unhealthy dietary behavior and inappropriate lifestyle habits. University students should be educated regarding the importance of balanced diet and healthy lifestyle, which are critical for effectual primary prevention of numerous chronic degenerative diseases. Furthermore, it is necessary to raise awareness concerning adverse effects of internet addiction among youth and their parents.

Keywords: dietary behavior, internet addiction, lifestyle, university students

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Authors: J. Woźniak-Holecka, T. Holecki, S. Jaruga

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Spa treatment is an important area of the health care system in Poland due to the increasing needs of the population and the context of historical conditions for this form of therapy. It extends the range of financing possibilities of the outlets and increases the potential of spa services, which is very important in the context of demographic and epidemiological changes. The main advantages of spa treatment services include its relatively wide availability, low risk of side effects, good patient tolerance, long-lasting curative effect and a relatively low cost. In addition, patients should be provided with a proper diet and enable participation in health education and health promotion classes aimed at health problems consistent with the treatment profile. Challenges for global health care systems include a sharp increase in spending on benefits, dynamic development of health technologies and growing social expectations. This requires extending the competences of health resort facilities for health promotion. Within each type of health resort institutions in Poland, nutritional education services are implemented, aimed at creating and consolidating proper eating habits. Choosing the right diet can speed up recovery or become one of the methods to alleviate the symptoms of chronic diseases. During spa treatment patient learns the principles of rational nutrition and adequate dietotherapy to his diseases. The aim of the project is to assess the frequency and quality of nutritional education provided to patients in health resort facilities in a nationwide perspective. The material for the study will be data obtained as part of an in-depth interview conducted among Heads of Nutrition Departments of selected institutions. The use of nutritional education in a health resort may be an important goal of implementing the state health policy as a useful tool to reduce the risk of diet-related diseases. Recognizing nutritional education in health resort institutions as a type of full-value health service can be effective system support for health policy, including seniors, due to demographic changes currently occurring in the Polish population. Furthermore, it is necessary to increase the interest and motivation of patients to follow the recommendations of nutritional education, because it will bring tangible benefits for the long-term effects of therapy and care should be taken for the form and methodology of nutrition education implemented in health resort institutions. Finally it is necessary to construct an educational offer in terms of selected groups of patients with the highest health needs: the elderly and the disabled. In conclusion, it can be said that the system of nutritional education implemented in polish health resort institutions should be subjected to global changes and strong systemic correction.

Keywords: health care system, nutritional education, public health, spa and treatment

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Authors: Julia Gontar, Natalia Buderatskaya, Igor Ilyin, Olga Parnitskaya, Sergey Lavrynenko, Eduard Kapustin, Ekaterina Ilyina, Yana Lakhno

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Introduction: It is well known that oocytes obtained from older reproductive women have accumulated mitochondrial DNA mutations, which negatively affects the morphology of a developing embryo and may lead to the birth of a child with mitochondrial disease. Special techniques have been developed to allow a donor oocyte cytoplasmic transfer with the parents’ biological nuclear DNA retention. At the same time, it is important to understand whether the procedure affects the future embryonic chromosome sets as the nuclear DNA is the transfer subject in this new complex procedure. Material and Methods: From July 2015 to July 2016, the investigation was carried out in the Medical Centre IGR. 34 donor oocytes (group A) were used for the manipulation with the aim of donating cytoplasm: 21 oocytes were used for zygotes pronuclear transfer and oocytes 13 – for the spindle transfer. The mean age of the oocyte donors was 28.4±2.9 years. The procedure was performed using Nikon Ti Eclipse inverted microscope equipped with the micromanipulators Narishige system (Japan), Saturn 3 laser console (UK), Oosight imaging systems (USA). For the preimplantation genetic screening (PGS) blastocyst biopsy was performed, trophectoderm samples were diagnosed using fluorescent in situ hybridization on chromosomes 9, 13, 15, 16, 17, 18, 21, 22, X, Y. For comparison of morphological characteristics and euploidy, was chosen a group of embryos (group B) with the amount of 121 blastocysts obtained from 213 oocytes, which were gotten from the donor programs of assisted reproductive technologies (ART). Group B was not subjected to donor oocyte cytoplasmic transfer procedure and studied on the above mentioned chromosomes. Statistical analysis was carried out using the criteria t, x^2 at a significance levels p<0.05, p<0.01, p<0.001. Results: After the donor cytoplasm transfer process the amount of the third day developing embryos was 27 (79.4%). In this stage, the group B consisted of 189 (88.7%) developing embryos, and there was no statistically significant difference (SSD) between the two groups (p>0.05). After a comparative analysis of the morphological characteristics of the embryos on the fifth day, we also found no SSD among the studied groups (p>0.05): from 34 oocytes exposed to manipulation, 14 (41.2%) blastocysts was obtained, while the group B blastocyst yield was 56.8% (n=121) from 213 oocytes. The following results were obtained after PGS performing: in group A euploidy in studied chromosomes were 28.6%(n=4) blastocysts, whereas in group B this rate was 40.5%(n=49), 28.6%(n=4) and 21.5%(n=26) of mosaic embryos and 42.8%(n=6) and 38.0%(n=46) aneuploid blastocysts respectively were identified. None of these specified parameters had an SSD (p>0.05). But attention was drawn by the blastocysts in group A with identified mosaicism, which was chaotic without any cell having euploid chromosomal set, in contrast to the mosaic embryos in group B where identified chaotic mosaicism was only 2.5%(n=3). Conclusions: According to the obtained results, there is no direct procedural effect on the chromosome in embryos obtained following donor oocyte cytoplasmic transfer. Thus, the technology introduction will enhance the infertility treating effectiveness as well as avoiding having a child with mitochondrial disease.

Keywords: donor oocyte cytoplasmic transfer, embryos’ chromosome set, oocyte spindle transfer, pronuclear transfer

Procedia PDF Downloads 299