Search results for: pre-extensive drug resistant

Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

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Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

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Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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Authors: Kathryn Nderitu, Atunga Nyachieo, Ezekiel Mecha

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Introduction: Solanum nigrum , also known as black nightshade, biosynthesizes various phytochemical compounds with various pharmacological activities, including treating cardiovascular diseases and type 2 diabetes, among others. Materials and Methods: To assess the anti-obesity effects of Solanum nigrum using high-fat-fed diet rats, Sprague Dawley male rats (n = 35) of weights 160–180 g were assigned randomly into seven groups comprising n = 5 rats each. Each group was fed for 11 weeks as follows: normal group (normal chow rat feed); high-fat diet control (HFD); HFD and standard drug (Orlistat 30 mg/kg bw); HFD and methanolic extract 150 mg/kgbw; HFD and methanolic extract 300 mg/kgbw; HFD and dichloromethane extract 150 mg/kgbw; HFD and dichloromethane extract 300 mg/kgbw. Body mass index and food intake were monitored per week, and an oral glucose tolerance test was measured in weeks 5 and 10. Lipid profiles, liver function tests, adipose tissue, liver weights, and phytochemical analysis of Solanum nigrum were later carried out. Results: High-fat diet control group rats exhibited a significant increase in body mass index (BMI), while rats administered with leaf extracts of Solanum nigrum showed a reduction in BMI. Both low doses of dichloromethane (150 mg/kgbw) and high doses of methanol extracts (300 mg/kgbw) showed a better reduction in BMI than the other treatment groups. A significant decrease (p <0.05) in low-density lipoprotein-cholesterol, triglycerides, and cholesterol was observed among the rats administered with Solanum nigrum extracts compared to those of HFD control. Moreover, the HFD control group significantly increased liver and adipose tissue weights compared to other treatment groups (p<0.05). Solanum nigrum also decreased glycemic levels and normalized the hepatic enzymes of HFD control. However, food intake among the groups showed no significant difference (p>0.05). Qualitative analysis of Solanum nigrum leaf extracts indicated the presence of various bioactive compounds associated with anti-obesity. Conclusion: These results validate the use of Solanum nigrum in controlling obesity.

Keywords: solanum nigrum, High fat diet, phytocompounds, obesity

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Authors: N. Manjunatha, K. T. Rangswamy, N. Nagaraju, H. A. Prameela, P. Rudraswamy, M. Krishnareddy

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The identification of virus in cowpea especially potyviruses is confusing. Even though there are several studies on viruses causing diseases in cowpea, difficult to distinguish based on symptoms and serological detection. The differentiation of potyviruses considering as a constraint, the present study is initiated for molecular characterization, host plant resistance and epidemiology of the BCMV infecting cowpea. The etiological agent causing cowpea mosaic was identified as Bean Common Mosaic Virus (BCMV) on the basis of RT-PCR and electron microscopy. An approximately 750bp PCR product corresponding to coat protein (CP) region of the virus and the presence of long flexuous filamentous particles measuring about 952 nm in size typical to genus potyvirus were observed under electron microscope. The characterized virus isolate genome had 10054 nucleotides, excluding the 3’ terminal poly (A) tail. Comparison of polyprotein of the virus with other potyviruses showed similar genome organization with 9 cleavage sites resulted in 10 functional proteins. The pairwise sequence comparison of individual genes, P1 showed most divergent, but CP gene was less divergent at nucleotide and amino acid level. A phylogenetic tree constructed based on multiple sequence alignments of the polyprotein nucleotide and amino acid sequences of cowpea BCMV and potyviruses showed virus is closely related to BCMV-HB. Whereas, Soybean variant of china (KJ807806) and NL1 isolate (AY112735) showed 93.8 % (5’UTR) and 94.9 % (3’UTR) homology respectively with other BCMV isolates. This virus transmitted to different leguminous plant species and produced systemic symptoms under greenhouse conditions. Out of 100 cowpea genotypes screened, three genotypes viz., IC 8966, V 5 and IC 202806 showed immune reaction in both field and greenhouse conditions. Single marker analysis (SMA) was revealed out of 4 SSR markers linked to BCMV resistance, M135 marker explains 28.2 % of phenotypic variation (R2) and Polymorphic information content (PIC) value of these markers was ranged from 0.23 to 0.37. The correlation and regression analysis showed rainfall, and minimum temperature had significant negative impact and strong relationship with aphid population, whereas weak correlation was observed with disease incidence. Path coefficient analysis revealed most of the weather parameters exerted their indirect contributions to the aphid population and disease incidence except minimum temperature. This study helps to identify specific gaps in knowledge for researchers who may wish to further analyse the science behind complex interactions between vector-virus and host in relation to the environment. The resistant genotypes identified are could be effectively used in resistance breeding programme.

Keywords: cowpea, epidemiology, genotypes, virus

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Authors: N. Gopal, K. Jaasminerjiit, L. Z. Xiang

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Quinazoline-4(3H)-one ring system has been consistently regarded as promising privileged structural icon owing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occurring alkaloids. The literature reveals that 2nd & 3rd positions of the quinazolin-4(3H)-one pharmacophore are the target for substitution with other moieties. On the other hand, sulphanilamide derivatives and isatin moiety also displayed valuable biological activities. Hence, it was thought worthwhile to study the effects of three pharmacophoric moieties like quinazolinone, sulphanilamide and isatin in a single molecule for the better analgesic activity with lower toxicity. Series of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives have been synthesised from the intermediate Schiff base of 2-(4’-substitutedphenyl)-3-[(N-2-oxoindolin-3-ylidene)-4”-sulphonamidophenyl]-quinazolin-4(3H)-one derivatives, which was prepared from reacting 2-(substituted phenyl)-4H-benzo[d][1,3]-oxazin-4-one with sulphanilamide. The required benzoxazinone derivatives were prepared by reacting anthranilic acid with benzoyl chloride. All the compounds structure was characterised by using H1 NMR, IR and Mass spectroscopy. The intermediate Schiff base and final Mannich base compounds were evaluated for their analgesic activity by acetic acid-induced writhing method at the dose of 25mg/kg, 50 mg/kg, and 100 mg/kg (bw) and Diclofenac (25mg/kg of body weight) will be used as the reference drugs. From the results of the study, it has been observed that final Mannich base showed a better analgesic activity when compared to the parent Schiff bases, it was found that compound substituted with N-methyl piperazine at 1st position of the indole nucleus of the final quinazolinone derivatives (GA4B1) i.e. 2-(4’-methoxy phenyl)-3-[4-(N-(1-N-methyl piperazine amine) methyl-2-oxo indoilin-3-ylidene] benzenesulfonyl quinazolin-4(3H)-one increases the analgesic activity and among the synthesised compounds, GA4B1 exhibited quite superior analgesic activity. The remaining Schiff bases and Mannich base derivatives exhibited moderate analgesic activity. All the compounds showed a dose dependent activity. None of the synthesised compound showed ulcer index whereas the standard drug, diclofenac [25 mg/kg (bw)] showed significantly higher gross ulcer index values.

Keywords: analgesic activity, isatin, mannich base, quinazolin-4(3H)-one

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Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

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Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

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Authors: Vita Krungleviciute, Rasa Zelvyte, Ingrida Monkeviciene, Jone Kantautaite, Rolandas Stankevicius, Modestas Ruzauskas, Elena Bartkiene

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The environmental impact of agricultural bioproducts from the processing of food crops is an increasing concern worldwide. Currently, cereal bran has been used as a low-value ingredient for both human consumption and animal feed. The most popular bioprocessing technologies for cereal bran nutritional and technological functionality increasing are enzymatic processing and fermentation, and the most popular starters in fermented feed production are lactic acid bacteria (LAB) including pediococci. However, the ruminant digestive system is unique, there are billions of microorganisms which help the cow to digest and utilize nutrients in the feed. To achieve efficient feed utilization and high milk yield, the microorganisms must have optimal conditions, and the disbalance of this system is highly undesirable. Pediococcus strains Pediococcus acidilactici BaltBio01 and Pediococcus pentosaceus BaltBio02 from spontaneous fermented rye were isolated (by rep – PCR method), identified, and characterized by their growth (by Thermo Bioscreen C automatic turbidometer), acidification rate (2 hours in 2.5 pH), gas production (Durham method), and carbohydrate metabolism (by API 50 CH test ). Antimicrobial activities of isolated pediococcus against variety of pathogenic and opportunistic bacterial strains previously isolated from diseased cattle, and their resistance to antibiotics were evaluated (EFSA-FEEDAP method). The isolated pediococcus strains were cultivated in barley/wheat bran (90 / 10, m / m) substrate, and developed supplements, with high content of valuable pediococcus, were used for Lithuanian black and white dairy cows feeding. In addition, the influence of supplements on milk production and composition was determined. Milk composition was evaluated by the LactoScope FTIR” FT1.0. 2001 (Delta Instruments, Holland). P. acidilactici BaltBio01 and P. pentosaceus BaltBio02 demonstrated versatile carbohydrate metabolism, grown at 30°C and 37°C temperatures, and acidic tolerance. Isolated pediococcus strains showed to be non resistant to antibiotics, and having antimicrobial activity against undesirable microorganisms. By barley/wheat bran utilisation using fermentation with selected pediococcus strains, it is possible to produce safer (reduced Enterobacteriaceae, total aerobic bacteria, yeast and mold count) feed stock with high content of pediococcus. Significantly higher milk yield (after 33 days) by using pediococcus supplements mix for dairy cows feeding could be obtained, while similar effect by using separate strains after 66 days of feeding could be achieved. It can be stated that barley/wheat bran could be used for higher value feed production in order to increase milk production. Therefore, further research is needed to identify what is the main mechanism of the positive action.

Keywords: barley/wheat bran, dairy cattle, fermented feed, milk, pediococcus

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Authors: V. Schmidt, L. Janovák, N. Wiegand, B. Patczai, K. Turzó

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Large bone defects are not able to heal spontaneously. Bioactive glasses seem to be appropriate (bio)materials for bone reconstruction. Bioactive glasses are osteoconductive and osteoinductive, therefore, play a useful role in bony regeneration and repair. Because of their not optimal mechanical properties (e.g., brittleness, low bending strength, and fracture toughness), their applications are limited. Bioactive glass can be used as a coating material applied on metal surfaces. In this way -when using them as implants- the excellent mechanical properties of metals and the biocompatibility and bioactivity of glasses will be utilized. Furthermore, ion release effects of bioactive glasses regarding osteogenic and angiogenic responses have been shown. Silicate bioactive glasses (45S5 Bioglass) induce the release and exchange of soluble Si, Ca, P, and Na ions on the material surface. This will lead to special cellular responses inducing bone formation, which is favorable in the biointegration of the orthopedic prosthesis. The incorporation of other additional elements in the silicate network such as fluorine, magnesium, iron, silver, potassium, or zinc has been shown, as the local delivery of these ions is able to enhance specific cell functions. Although hip and knee prostheses present a high success rate, bacterial infections -mainly implant associated- are serious and frequent complications. Infection can also develop after implantation of hip prostheses, the elimination of which means more surgeries for the patient and additional costs for the clinic. Prosthesis-related infection is a severe complication of orthopedic surgery, which often causes prolonged illness, pain, and functional loss. While international efforts are made to reduce the risk of these infections, orthopedic surgical infections (SSIs) continue to occur in high numbers. It is currently estimated that up to 2.5% of primary hip and knee surgeries and up to 20% of revision arthroplasties are complicated by periprosthetic joint infection (PJIs). According to some authors, these numbers are underestimated, and they are also increasing. Staphylococcus aureus is the leading cause of both SSIs and PJIs, and the prevalence of methicillin-resistant S. aureus (MRSA) is on the rise, particularly in the United States. These deep infections lead to implant removal and consequently increase morbidity and mortality. The study targets this clinical problem using our experience so far with the Ag-doped polymer coatings on Titanium implants. Non-modified or modified (e.g., doped with antibacterial agents, like Ag) bioactive glasses could play a role in the prevention of infections or the therapy of infected tissues. Bioactive glasses have excellent biocompatibility, proved by in vitro cell culture studies of human osteoblast-like MG-63 cells. Ag-doped bioactive glass-scaffold has a good antibacterial ability against Escherichia coli and other bacteria. It may be concluded that these scaffolds have great potential in the prevention and therapy of implant-associated bone infection.

Keywords: antibacterial agents, bioactive glass, hip and knee prosthesis, medical implants

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Authors: Kai-Shiang Chang, Shiao-Shing Chen, Saikat Sinha Ray, Hung-Te Hsu

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In recent years, membrane bioreactors (MBR) have been widely utilized as it can effectively replace conventional activated sludge process (CAS). Membrane bioreactor (MBR) is found to be more effective technology compared to other conventional activated sludge process and advanced membrane separation technique. Additionally, as far as the MBR is concerned, it is having excellent control of sludge retention time (SRT) and hydraulic retention time (HRT) and conducive to the retention of high concentration of sludge biomass. The membrane bioreactor (MBR) can effectively reduce footprint in terms of area and omit the secondary processing procedures in the conventional activated sludge process (CAS). Currently, as per the membrane technology, the ceramic membrane is found to have highly strong anti-acid-base properties, and it is more suitable than polymeric membrane while using for backwash and chemical cleaning. This study is based upon the treatment of Cutting Fluid wastewater, as the Cutting Fluid is widely used in the cutting equipment. However, the Cutting Fluid wastewater is very difficult to treat. In this study, the ceramic membrane was used and combine with of MBR system to treat the Cutting Fluid wastewater. In this present study, different kind of chemical coagulants have been utilized for pretreatment purpose in order to get the supernatant and simultaneously this wastewater (supernatant) was treated by MBR process. Nevertheless, ceramic membrane has three advantages such as high mechanical strength, drug resistance and reuse. During the experiment, the backwash technique was used for every interval of 10 minutes in order to avoid fouling of the membrane. In this study, during pretreatment the Chemical Oxygen Demand (COD) removal efficiency was found to be 71-86% and oil removal efficiency was analyzed to be 83-92%. This pretreatment study suggests that it is quiet effective methodology to reduce COD and oil concentration. Finally, In the MBR system when the HRT is more than 7.5 hour, the COD removal efficiency was found to be 87-93% and could achieve 100% oil removal efficiency. Coagulation test series were seen in Refs coagulants for the treatment of wastewater containing cutting oil with better oil and COD removal efficiency. The results also showed that the oil removal efficiency in the MBR system could reduce the oil content to less than 1 mg / L when the oil quality was 126 mg / L. Therefore, in this paper, the performance of membrane bioreactor by utilizing ceramic membrane has been demonstrated for treatment of Cutting Fluid wastewater.

Keywords: membrane bioreactor, cutting fluid, oil, chemical oxygen demand

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Authors: Erick R. Bandala, Kebret Kebede, Nicole Johnson, Rebecca Murray, Destiny Green, John Mejia, Polioptro Martinez-Austria

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Summertemperature data from Clark County was collected and used to estimate two different heat-related indexes: the heat index (HI) and excess heat factor (EHF). These two indexes were used jointly with data of health-related deaths in Clark County to assess the effect of extreme heat on the exposed population. The trends of the heat indexes were then analyzed for the 2007-2016 decadeandthe correlation between heat wave episodes and the number of heat-related deaths in the area was estimated. The HI showed that this value has increased significantly in June, July, and August over the last ten years. The same trend was found for the EHF, which showed a clear increase in the severity and number of these events per year. The number of heat wave episodes increased from 1.4 per year during the 1980-2016 period to 1.66 per yearduring the 2007-2016 period. However, a different trend was found for heat-wave-event duration, which decreasedfrom an average of 20.4 days during the trans-decadal period (1980-2016) to 18.1 days during the most recent decade(2007-2016). The number of heat-related deaths was also found to increase from 2007 to 2016, with 2016 with the highest number of heat-related deaths. Both HI and the number of deaths showeda normal-like distribution for June, July, and August, with the peak values reached in late July and early August. The average maximum HI values better correlated with the number of deaths registered in Clark County than the EHF, probably because HI uses the maximum temperature and humidity in its estimation,whereas EHF uses the average medium temperature. However, it is worth testing the EHF of the study zone because it was reported to fit properly in the case of heat-related morbidity. For the overall period, 437 heat-related deaths were registered in Clark County, with 20% of the deaths occurring in June, 52% occurring in July, 18% occurring in August,and the remaining 10% occurring in the other months of the year. The most vulnerable subpopulation was people over 50 years old, for which 76% of the heat-related deaths were registered.Most of the cases were associated with heart disease preconditions. The second most vulnerable subpopulation was young adults (20-50), which accounted for 23% of the heat-related deaths. These deathswere associated with alcoholic/illegal drug intoxication.

Keywords: heat, health, hazards, workforce

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Authors: Muhammad Umer Mehmood, Muhammad Luqman, Muhammad Yaseen, Imtiaz Hussain

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Climate change is an arduous fact, which could not be unheeded easily. It is a phenomenon which has brought a collection of challenges for the mankind. Scientists have found many of its negative impacts on the life of human being and the resources on which the life of humanity is dependent. There are many issues which are associated with the factor of prime importance in this study, 'climate change'. Whenever changes happen in nature, they strike the whole globe. Effects of these changes vary from region to region. Climate of every region of this globe is different from the other. Even within a state, country or the province has different climatic conditions. So it is mandatory that the response in that specific region and the coping strategy of this specific region should be according to the prevailing risk. In the present study, the objective was to assess the coping strategies and vulnerability of small landholders. So that a professional suggestion could be made to cope with the vulnerability factor of small farmers. The cross-sectional research design was used with the intervention of quantitative approach. The study was conducted in the Khanewal district, of Punjab, Pakistan. 120 small farmers were interviewed after randomized sampling from the population of respective area. All respondents were above the age of 15 years. A questionnaire was developed after keen observation of facts in the respective area. Content and face validity of the instrument was assessed with SPSS and experts in the field. Data were analyzed through SPSS using descriptive statistics. From the sample of 120, 81.67% of the respondents claimed that the environment is getting warmer and not fit for their present agricultural practices. 84.17% of the sample expressed serious concern that they are disturbed due to change in rainfall pattern and vulnerability towards the climatic effects. On the other hand, they expressed that they are not good at tackling the effects of climate change. Adaptation of coping strategies like change in cropping pattern, use of resistant varieties, varieties with minimum water requirement, intercropping and tree planting was low by more than half of the sample. From the sample 63.33% small farmers said that the coping strategies they adopt are not effective enough. The present study showed that subsistence farming, lack of marketing and overall infrastructure, lack of access to social security networks, limited access to agriculture extension services, inappropriate access to agrometeorological system, unawareness and access to scientific development and low crop yield are the prominent factors which are responsible for the vulnerability of small farmers. A comprehensive study should be conducted at national level so that a national policy could be formulated to cope with the dilemma in future with relevance to climate change. Mainstreaming and collaboration among the researchers and academicians could prove beneficiary in this regard the interest of national leaders’ does matter. Proper policies to avoid the vulnerability factors should be the top priority. The world is taking up this issue with full responsibility as should we, keeping in view the local situation.

Keywords: adaptation, coping strategies, climate change, Pakistan, small farmers, vulnerability

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Authors: Valeria Abreu Minero, Edward Barker, Hannah Dickson, Francois Husson, Sandra Flynn, Jennifer Shaw

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Purpose – The purpose of this paper is to identify offender typologies based on aspects of the offenders’ psychopathology and their associations with crime scene behaviours using data derived from the National Confidential Enquiry into Suicide and Safety in Mental Health concerning homicides in England and Wales committed by offenders in contact with mental health services in the year preceding the offence (n=759). Design/methodology/approach – The authors used multiple correspondence analysis to investigate the interrelationships between the variables and hierarchical agglomerative clustering to identify offender typologies. Variables describing: the offender’s mental health history; the offenders’ mental state at the time of offence; characteristics useful for police investigations; and patterns of crime scene behaviours were included. Findings – Results showed differences in the offender’s histories in relation to their crime scene behaviours. Further, analyses revealed three homicide typologies: externalising, psychosis and depression. Analyses revealed three homicide typologies: externalising, psychotic and depressive. Practical implications – These typologies may assist the police during homicide investigations by: furthering their understanding of the crime or likely suspect; offering insights into crime patterns; provide advice as to what an offender’s offence behaviour might signify about his/her mental health background; findings suggest information concerning offender psychopathology may be useful for offender profiling purposes in cases of homicide offenders with schizophrenia, depression and comorbid diagnosis of personality disorder and alcohol/drug dependence. Originality/value – Empirical studies with an emphasis on offender profiling have almost exclusively focussed on the inference of offender demographic characteristics. This study provides a first step in the exploration of offender psychopathology and its integration to the multivariate analysis of offence information for the purposes of investigative profiling of homicide by identifying the dominant patterns of mental illness within homicidal behaviour.

Keywords: offender profiling, mental illness, psychopathology, multivariate analysis, homicide, crime scene analysis, crime scene behviours, investigative advice

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Authors: Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Kemal Aygun, Ecem Deniz Kırkpantur, Ozge Ecmel Onur

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Although the mechanism of action is not well known, Intravenous Lipid Emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that ILE probably separate the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high dose free fatty acids activating the voltage gated calcium channels in the myocytes. In this study, the effects of ILE treatment on digoxin overdose which are frequently observed in emergency departments was searched in an animal model in terms of cardiac side effects and survival. The study was carried out at Yeditepe University, Faculty of Medicine-Experimental Animals Research Center Labs in December 2015. 40 Sprague-Dawley rats weighing 300-400 g were divided into 5 groups randomly. As the pre-treatment, the first group received saline, the second group received lipid, the third group received DigiFab, and the fourth group received DigiFab and lipid. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest occurrence times were recorded. As no medication causing arrhythmia was infused, Group 5 was excluded from the statistical analysis performed for the comparisons of first arrhythmia and death time. According to the results although there was no significant difference in the statistical analysis comparing the four groups, as the rats, only exposed to digoxin intoxication were compared with the rats pre-treated with ILE in terms of first arrhythmia time and cardiac arrest occurrence times, significant difference was observed between the groups. According to our results, using DigiFab treatment, intralipid treatment, intralipid and DigiFab treatment for the rats exposed to digoxin intoxication makes no significant difference in terms of the first arrhythmia and death occurrence time. However, it is not possible to say that at the doses we use in the study, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the inter-comparisons of all the groups, the study should be repeated in the larger groups.

Keywords: arrhytmia, cardiac arrest, DigiFab, digoxin intoxication

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Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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Authors: Pei-Ru Yang, Yu-Chen Lin, Jia-Min Wu

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Background: A 58-year-old man with a history of osteoporosis and diabetes presented with chronic pain in his left knee due to severe knee joint degeneration. The knee replacement surgery was recommended by the doctor. But the patient suffered from low pain tolerance and wondered if virtual reality could relieve acute postoperative wound pain. Methods: We used the PICO (patient, intervention, comparison, and outcome) approach to generate indexed keywords and searched systematic review articles from 2017 to 2021 on the Cochran Library, PubMed, and Clinical Key databases. Results: The initial literature results included 38 articles, including 12 Cochrane library articles and 26 PubMed articles. One article was selected for further analysis after removing duplicates and off-topic articles. The eight trials included in this article were published between 2013 and 2019 and recruited a total of 723 participants. The studies, conducted in India, Lebanon, Iran, South Korea, Spain, and China, included adults who underwent hemorrhoidectomy, dental surgery, craniotomy or spine surgery, episiotomy repair, and knee surgery, with a mean age (24.1 ± 4.1 to 73.3 ± 6.5). Virtual reality is an emerging non-drug postoperative analgesia method. The findings showed that pain control was reduced by a mean of 1.48 points (95% CI: -2.02 to -0.95, p-value < 0.0001) in minor surgery and 0.32 points in major surgery (95% CI: -0.53 to -0.11, p-value < 0.03), and the overall postoperative satisfaction has improved. Discussion: Postoperative pain is a common clinical problem in surgical patients. Research has confirmed that virtual reality can create an immersive interactive environment, communicate with patients, and effectively relieve postoperative pain. However, virtual reality requires the purchase of hardware and software and other related computer equipment, and its high cost is a disadvantage. We selected the best literature based on clinical questions to answer the patient's question and used share decision making (SDM) to help the patient make decisions based on the clinical situation after knee replacement surgery to improve the quality of patient-centered care.

Keywords: knee replacement surgery, postoperative pain, share decision making, virtual reality

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Authors: Aijing Luo, Zirui Xin, Yifeng Yuan

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Background: With the rapid development of the online health community, more and more patients or families are seeking health information on the Internet. Objective: This study aimed to discuss how to fully reveal the health information needs expressed by hypertensive patients in their questions in the online environment. Methods: This study randomly selected 1,000 text records from the question data of hypertensive patients from 2008 to 2018 collected from the website www.haodf.com and constructed a classification system through literature research and content analysis. This paper identified the background characteristics and questioning the intention of each hypertensive patient based on the patient’s question and used co-occurrence network analysis to explore the features of the health information needs of hypertensive patients. Results: The classification system for health information needs of patients with hypertension is composed of 9 parts: 355 kinds of drugs, 395 kinds of symptoms and signs, 545 kinds of tests and examinations , 526 kinds of demographic data, 80 kinds of diseases, 37 kinds of risk factors, 43 kinds of emotions, 6 kinds of lifestyles, 49 kinds of questions. The characteristics of the explored online health information needs of the hypertensive patients include: i)more than 49% of patients describe the features such as drugs, symptoms and signs, tests and examinations, demographic data, diseases, etc. ii) these groups are most concerned about treatment (77.8%), followed by diagnosis (32.3%); iii) 65.8% of hypertensive patients will ask doctors online several questions at the same time. 28.3% of the patients are very concerned about how to adjust the medication, and they will ask other treatment-related questions at the same time, including drug side effects, whether to take drugs, how to treat a disease, etc.; secondly, 17.6% of the patients will consult the doctors online about the causes of the clinical findings, including the relationship between the clinical findings and a disease, the treatment of a disease, medication, and examinations. Conclusion: In the online environment, the health information needs expressed by Chinese hypertensive patients to doctors are personalized; that is, patients with different background features express their questioning intentions to doctors. The classification system constructed in this study can guide health information service providers in the construction of online health resources, to help solve the problem of information asymmetry in communication between doctors and patients.

Keywords: online health community, health information needs, hypertensive patients, doctor-patient communication

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Authors: Ersumo Tessema, Bogale Girmaye Tamrat, Mohammed Burka

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Background: Hyperthyroidism is a common thyroid disorder especially in women and characterized by increased thyroid hormone synthesis and secretion. The disorder manifests predominantly as Graves’ disease in iodine-sufficient areas and has increasing prevalence in iodine-deficient countries in patients with nodular thyroid disease and following iodine fortification. In Ethiopia, the magnitude of the disorder is unknown and, in Africa, due to scarcity of resources, its management remains suboptimal. Objective: The aim of this study was to analyze the pattern and management of patients with hyperthyroidism at the United Vision Medical Services Center, Addis Ababa between August 30, 2013, and February 1, 2018. Patients and methods: The study was a retrospective analysis of medical records of all patients with hyperthyroidism at the United Vision Private Medical Services Center, Addis Ababa. A questionnaire was filled out; the collected data entered into a computer and statistically analyzed using the SPSS package. The results were tabulated and discussed with literature review. Results: A total of 589 patients were included in this study. The median age was 40 years, and the male to female ratio was 1.0:7.9. Most patients (93%) presented with goiter and the associated features of toxic goiter except weight loss, sweating and tachycardia were uncommon. Majority of patients presented more than two years after the onset of their presenting symptoms. The most common physical finding (91%), as well as diagnosis, was toxic nodular goiter. The most frequent (83%) derangement in the thyroid function tests was a low thyroid-stimulating hormone, and the most commonly (94%) used antithyroid drug was a propylthiouracil. The most common (96%) surgical procedure in 213 patients was a near-total thyroidectomy with a postoperative course without incident in 92% of all the patients. Conclusion: The incidence and prevalence of hyperthyroidism are apparently on the increase in Addis Ababa, which may be related to the existing severe iodine-deficiency and or the salt iodation program (iodine-induced hyperthyroidism). Hyperthyroidism predominantly affects women and, in surgical services, toxic nodular goiter is more common than diffuse goiter, and the treatment of choice in experienced hands is a near-total thyroidectomy.

Keywords: Ethiopia, grave’s disease, hyperthyroidism, toxic nodular goiter

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Authors: Geremew Geidare Kailo, Igor Gáspár, András Koris, Ivana Pajčin, Flóra Vitális, Vanja Vlajkov

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Three-dimension (3D) printing, a very popular additive manufacturing technology, has recently undergone rapid growth and replaced the use of conventional technology from prototyping to producing end-user parts and products. The 3D Printing technology involves a digital manufacturing machine that produces three-dimensional objects according to designs created by the user via 3D modeling or computer-aided design/manufacturing (CAD/CAM) software. The most popular 3D printing system is Fused Deposition Modeling (FDM) or also called Fused Filament Fabrication (FFF). A 3D-printed object is considered food safe if it can have direct contact with the food without any toxic effects, even after cleaning, storing, and reusing the object. This work analyzes the processing timeline of the filament (material for 3D printing) from unboxing to the extrusion through the nozzle. It is an important task to analyze the growth of bacteria on the 3D printed surface and in gaps between the layers. By default, the 3D-printed object is not food safe after longer usage and direct contact with food (even though they use food-safe filaments), but there are solutions for this problem. The aim of this work was to evaluate the 3D-printed object from different perspectives of food safety. Firstly, testing antimicrobial 3D printing filaments from a food safety aspect since the 3D Printed object in the food industry may have direct contact with the food. Therefore, the main purpose of the work is to reduce the microbial load on the surface of a 3D-printed part. Coating with epoxy resin was investigated, too, to see its effect on mechanical strength, thermal resistance, surface smoothness and food safety (cleanability). Another aim of this study was to test new temperature-resistant filaments and the effect of high temperature on 3D printed materials to see if they can be cleaned with boiling or similar hi-temp treatment. This work proved that all three mentioned methods could improve the food safety of the 3D printed object, but the size of this effect variates. The best result we got was with coating with epoxy resin, and the object was cleanable like any other injection molded plastic object with a smooth surface. Very good results we got by boiling the objects, and it is good to see that nowadays, more and more special filaments have a food-safe certificate and can withstand boiling temperatures too. Using antibacterial filaments reduced bacterial colonies to 1/5, but the biggest advantage of this method is that it doesn’t require any post-processing. The object is ready out of the 3D printer. Acknowledgements: The research was supported by the Hungarian and Serbian bilateral scientific and technological cooperation project funded by the Hungarian National Office for Research, Development and Innovation (NKFI, 2019-2.1.11-TÉT-2020-00249) and the Ministry of Education, Science and Technological Development of the Republic of Serbia. The authors acknowledge the Hungarian University of Agriculture and Life Sciences’s Doctoral School of Food Science for the support in this study

Keywords: food safety, 3D printing, filaments, microbial, temperature

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Authors: V. S. Bessa, I. S. Moreira, S. Murgolo, C. Piccirillo, G. Mascolo, P. M. L. Castro

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The occurrence of pharmaceuticals in the environment has been a topic of increasing concern. Pharmaceuticals are not completely mineralized in the human body and are released on the sewage systems as the pharmaceutical itself and as their “biologically active” metabolites through excretion, as well as by improper elimination and disposal. Conventional wastewater treatment plants (WWTPs) are not designed to remove these emerging pollutants and they are thus released into the environment. The antiepileptic drug carbamazepine (CBZ) and the non-steroidal anti-inflammatory diclofenac (DCF) are two widely used pharmaceuticals, frequently detected in water bodies, including rivers and groundwater, in concentrations ranging from ng L 1 to mg L 1. These two compounds were classified as medium to high-risk pollutants in WWTP effluents and surface waters. Also, CBZ has been suggested as a molecular marker of wastewater contamination in surface water and groundwater and the European Union included DCF in the watch list of substances Directive to be monitored. In the present study, biodegradation of CBZ and DCF by the bacterial strain Labrys portucalensis F11, a strain able to degrade other pharmaceutical compounds, was assessed; tests were performed with F11 as single carbon and energy source, as well as in presence of 5.9mM of sodium acetate. In assays supplemented with 2.0 and 4.0 µM of CBZ, the compound was no longer detected in the bulk medium after 24hr and 5days, respectively. Complete degradation was achieved in 21 days for 11.0 µM and in 23 days for 21.0 µM. For the highest concentration tested (43.0 µM), 95% of degradation was achieved in 30days. Supplementation with acetate increased the degradation rate of CBZ, for all tested concentrations. In the case of DCF, when supplemented as a single carbon source, approximately 70% of DCF (1.7, 3.3, 8.4, 17.5 and 34.0 µM) was degraded in 30days. Complete degradation was achieved in the presence of acetate for all tested concentrations, at higher degradation rates. The detection of intermediates produced during DCF biodegradation was performed by UPLC-QTOF/MS/MS, which allowed the identification of a range of metabolites. Stoichiometric liberation of chorine occurred and no metabolites were detected at the end of the biodegradation assays suggesting a complete mineralization of DCF. Strain Labrys portucalensis F11 proved to be able to degrade these two top priority environmental contaminants and may be potentially useful for biotechnological applications/environment remediation.

Keywords: biodegradation, carbamazepine, diclofenac, pharmaceuticals

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Authors: Adil Mustafa, Ahmet Erten, Alper Kiraz, Melikhan Tanyeri

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Work presented here is based on a novel experimental technique used to hydrodynamically trap oil microdroplets inside a microfluidic chip at the junction of microchannels known as stagnation point. Hydrodynamic trapping has been recently used to trap and manipulate a number of particles starting from microbeads to DNA and single cells. Benzyl Benzoate (BB) is used as droplet material. The microdroplets are trapped individually at stagnation point and their dissolution was observed. Experiments are performed for two concentrations (10mM or 10µM) of AOT surfactant (Docusate Sodium Salt) and two flow rates for each case. Moreover, experimental data is compared with Zhang-Yang-Mao (ZYM) model which studies dissolution of liquid microdroplets in the presence of a host fluid experiencing extensional creeping flow. Industrial processes like polymer blending systems in which heat or mass transport occurs experience extensional flow and an insight into these phenomena is of significant importance to many industrial processes. The experimental technique exploited here gives an insight into the dissolution of liquid microdroplets under extensional flow regime. The comparison of our experimental results with ZYM model reveals that dissolution of microdroplets at lower surfactant concentration (10µM) fits the ZYM model at saturation concentration (Cs) value reported in literature (Cs = 15×10⁻³Kg\m³) while for higher surfactant concentration (10mM) which is also above the critical micelle concentration (CMC) of surfactant (5mM) the data fits ZYM model at (Cs = 45×10⁻³Kg\m³) which is 3X times the value reported in literature. The difference in Cs value from the literature shows enhancement in dissolution rate of sparingly soluble BB microdroplets at surfactant concentrations higher than CMC. Enhancement in the dissolution of sparingly soluble materials is of great importance in pharmaceutical industry. Enhancement in the dissolution of sparingly soluble drugs is a key research area for drug design industry. The experimental method is also advantageous because it is robust and has no mechanical contact with droplets under study are freely suspended in the fluid as compared existing methods used for testing dissolution of drugs. The experiments also give an insight into CMC measurement for surfactants.

Keywords: extensional flow, hydrodynamic trapping, Zhang-Yang-Mao, CMC

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Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

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Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

Procedia PDF Downloads 173

Authors: Evelyn Ilabaca, Ximena Valenzuela, Alejandra Torres, María José Galotto, Abel Guarda

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One of the biggest problems in food packaging industry, especially with the plastic materials, is the fact that these materials are usually obtained from non-renewable resources and also remain as waste after its use, causing environmental issues. This is an international concern and particular attention is given to reduction, reuse and recycling strategies for decreasing the waste from plastic packaging industry. In general, polyethylenes represent most plastic waste and recycling process of post-consumer polyethylene terephthalate (PCR-PET) has been studied. US Food and Drug Administration (FDA), European Food Safety Authority (EFSA) and Southern Common Market (MERCOSUR) have generated different legislative documents to control the use of PCR-PET in the production of plastic packaging intended direct food contact in order to ensure the capacity of recycling process to remove possible contaminants that can migrate into food. Consequently, it is necessary to demonstrate by challenge test that the recycling process is able to remove specific contaminants, obtaining a safe recycled plastic to human health. These documents establish that the concentration limit for substitute contaminants in PET is 220 ppb (ug/kg) and the specific migration limit is 10 ppb (ug/kg) for each contaminant, in addition to assure the sensorial characteristics of food are not affected. Moreover, under the Commission Regulation (EU) N°10/2011 on plastic materials and articles intended to come into contact with food, it is established that overall migration limit is 10 mg of substances per 1 dm2 of surface area of the plastic material. Thus, the aim of this work is to determine the safety of PCR-PET-containing food packaging materials in Chile by measuring their overall migration, and their comparison with the established limits at international level. This information will serve as a basis to provide a regulation to control and regulate the use of recycled plastic materials in the manufacture of plastic packaging intended to be in direct contact with food. The methodology used involves a procedure according to EN-1186:2002 with some modifications. The food simulants used were ethanol 10 % (v/v) and acetic acid 3 % (v/v) as aqueous food simulants, and ethanol 95 % (v/v) and isooctane as substitutes of fatty food simulants. In this study, preliminary results showed that Chilean food packaging plastics with different PCR-PET percentages agree with the European Legislation for food aqueous character.

Keywords: contaminants, polyethylene terephthalate, plastic food packaging, recycling

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Authors: Ramin Mehdiabadi

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Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

Procedia PDF Downloads 150

Authors: Govind Kumar

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The concept of ‘e-governance’ that was brought about by the new wave of reforms, namely ‘LPG’ in the early 1990s, has been enabling governments across the globe to digitally transform themselves. Digital transformation is leading the governments with qualitative decisions, optimization in rational use of resources, facilitation of cost-benefit analyses, and elimination of redundancy and corruption with the help of ICT-based applications interface. ICT-based applications/technologies have enormous potential for impacting positive change in the social lives of the global citizenry. Supercomputers test and analyze millions of drug molecules for developing candidate vaccines to combat the global pandemic. Further, e-commerce portals help distribute and supply household items and medicines, while videoconferencing tools provide a visual interface between the clients and hosts. Besides, crop yields are being maximized with the help of drones and machine learning, whereas satellite data, artificial intelligence, and cloud computing help governments with the detection of illegal mining, tackling deforestation, and managing freshwater resources. Such e-applications have the potential to take governance an extra mile by achieving 5 Es (effective, efficient, easy, empower, and equity) of e-governance and six Rs (reduce, reuse, recycle, recover, redesign and remanufacture) of sustainable development. If such digital transformation gains traction within the government framework, it will replace the traditional administration with the digitalization of public administration. On the other hand, it has brought in a new set of challenges, like the digital divide, e-illiteracy, technological divide, etc., and problems like handling e-waste, technological obsolescence, cyber terrorism, e-fraud, hacking, phishing, etc. before the governments. Therefore, it would be essential to bring in a rightful mixture of technological and humanistic interventions for addressing the above issues. This is on account of the reason that technology lacks an emotional quotient, and the administration does not work like technology. Both are self-effacing unless a blend of technology and a humane face are brought in into the administration. The paper will empirically analyze the significance of the technological framework of digital transformation within the government set up for the digitalization of public administration on the basis of the synthesis of two case studies undertaken from two diverse fields of administration and present a future framework of the study.

Keywords: digital transformation, electronic governance, public administration, knowledge framework

Procedia PDF Downloads 81

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Ioan Rusu

Abstract:

In the operation of power transformers of 110 kV/MV from substations, these are traveled by fault current resulting from MV line damage. Defect electrical contacts are heated when they are travelled from fault currents. In the case of high temperatures when 135 °C is reached, the electrical insulating oil in the vicinity of the electrical faults comes into contact with these contacts releases gases, and activates the electrical protection. To avoid auto-flammability of electro-insulating oil, we designed a security system thermal of electrical contact defects by pouring fire-resistant polyurethane foam, mastic or mortar fire inside a cardboard electro-insulating cylinder. From practical experience, in the exploitation of power transformers of 110 kV/MT in oil electro-insulating were recorded some passing disconnecting commanded by the gas protection at internal defects. In normal operation and in the optimal load, nominal currents do not require thermal secure contacts inside electrical transformers, contacts are made at the fabrication according to the projects or to repair by solder. In the case of external short circuits close to the substation, the contacts inside electrical transformers, even if they are well made in sizes of Rcontact = 10^‑6 Ω, are subjected to short-circuit currents of the order of 10 kA-20 kA which lead to the dissipation of some significant second-order electric powers, 100 W-400 W, on contact. At some internal or external factors which action on electrical contacts, including electrodynamic efforts at short-circuits, these factors could be degraded over time to values in the range of 10^-4 Ω to 10^-5 Ω and if the action time of protection is great, on the order of seconds, power dissipation on electrical contacts achieve high values of 1,0 kW to 40,0 kW. This power leads to strong local heating, hundreds of degrees Celsius and can initiate self-ignition and burning oil in the vicinity of electro-insulating contacts with action the gas relay. Degradation of electrical contacts inside power transformers may not be limited for the duration of their operation. In order to avoid oil burn with gas release near electrical contacts, at short-circuit currents 10 kA-20 kA, we have outlined the following solutions: covering electrical contacts in fireproof materials that would avoid direct burn oil at short circuit and transmission of heat from electrical contact along the conductors with heat dissipation gradually over time, in a large volume of cooling. Flame retardant materials are: polyurethane foam, mastic, cement (concrete). In the normal condition of operation of transformer, insulating of conductors coils is with paper and insulating oil. Ignition points of its two components respectively are approximated: 135 °C heat for oil and 200 ⁰C for paper. In the case of a faulty electrical contact, about 10^-3 Ω, at short-circuit; the temperature can reach for a short time, a value of 300 °C-400 °C, which ignite the paper and also the oil. By burning oil, there are local gases that disconnect the power transformer. Securing thermal electrical contacts inside the transformer, in cardboard tube with polyurethane foams, mastik or cement, ensures avoiding gas release and also gas protection working.

Keywords: power transformer, oil insulatation, electric contacts, Bucholtz relay

Procedia PDF Downloads 139

Authors: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad

Abstract:

Predicting the risk of diabetic retinopathy (DR) in Indian type 2 diabetes patients is immensely necessary. India, being the second largest country after China in terms of a number of diabetic patients, to the best of our knowledge not a single risk score for complications has ever been investigated. Diabetic retinopathy is a serious complication and is the topmost reason for visual impairment across countries. Any type or form of DR has been taken as the event of interest, be it mild, back, grade I, II, III, and IV DR. A sample was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of DR. Cox proportional hazard regression is used to design risk scores for the prediction of retinopathy. Model calibration and discrimination are assessed from Hosmer Lemeshow and area under receiver operating characteristic curve (ROC). Overfitting and underfitting of the model are checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Optimal cut off point is chosen by Youden’s index. Five-year probability of DR is predicted by both survival function, and Markov chain two state model and the better technique is concluded. The risk scores developed can be applied by doctors and patients themselves for self evaluation. Furthermore, the five-year probabilities can be applied as well to forecast and maintain the condition of patients. This provides immense benefit in real application of DR prediction in T2DM.

Keywords: Cox proportional hazard regression, diabetic retinopathy, ROC curve, type 2 diabetes mellitus

Procedia PDF Downloads 163

Authors: Mohamad Shamsuri Juhari

Abstract:

Fathers who positively involve themselves in their children’s lives will have had a constructive influence on the latter’s social, behavioural, and psychological development. This paper will share the preliminary findings of an ongoing research project which investigates Singaporean fathers from the nation’s minority Malay-Muslim community who commit the reverse, that is, it intends to study the reasons behind these fathers’ non-involvement during the period of their children’s developing years be it through absence, disinterest or ignorance. For instance, children from homes with absentee fathers are more likely to develop deficiencies in attitude and conduct. A father’s negative show of parental skills can also cause setbacks in the child’s education, economic instability in the latter’s future family life, as well as the likelihood of an ensuing intergenerational transmission of criminal behaviour. In the context of the minority Singaporean Malay-Muslim community, the need to investigate the challenges faced by fathers from the ethnic group in carrying out their parental roles arose due to the perceptible rise in statistics reflecting delinquency among its youths. This has resulted in other associated issues such as teenage pregnancies (and the subsequent cyclical patterns of divorce and single motherhood), over-representation in the data for drug offences, and under-representation in statistics reflecting academic achievement. While other factors are known to be involved, these negative outcomes have also been attributed to the lack of fatherly guidance in the affected Malay families. This still-ongoing research project is being carried out in two phases: The first by means of secondary research as well as exploratory data collection via roundtable and focus group discussions with fathers from diverse socio-economic backgrounds. This sets the way for the second phase in which a survey will be undertaken, followed by a series of in-depth face-to-face interviews. The research findings will then be translated into intervention initiatives to overcome the identified challenges. Based on the results collated from Phase 1 of the research, this paper will share a ‘first look’ on the challenges to effective parenting faced by Malay-Muslim fathers in Singapore specifically those relating to the socio-cultural domains of attitude, knowledge, and practice.

Keywords: Malay fathers, socio-cultural domains, attitude, knowledge, practice

Procedia PDF Downloads 176