Search results for: oral delivery

Authors: Robert L. Williamson

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A 'token economy' refers to a method of positive behaviour support whereby ‘tokens’ are delivered to students as a reward for exhibiting specific behaviours. Students later exchange tokens to ‘purchase’ items of interest. Unfortunately, implementation fidelity can be problematic as some find physical delivery of tokens while teaching difficult. This project developed and tested a prototype, iPad-based tool that enabled teachers to deliver and track tokens electronically. Using an alternating treatment design, any differences in on-task individual and/or group behaviours between the virtual versus physical token delivery systems were examined. Results indicated that while students and teachers preferred iPad-based implementation, no significant difference was found concerning on-task behaviours of students between the two methodologies. Perhaps more interesting was that the teacher found implementation of both methods problematic and suggested a second person was most effective in implementing a token economy method. This would represent a significant cost to the effective use of such a method. Further research should focus on the use of a lay volunteer regarding method implementation fidelity and associated outcomes of the method.

Keywords: positive behaviour support, inclusion, token economy, applied behaviour analysis

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Arindam Roy

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Public policy is an intriguing terrain, which involves complex interplay of administrative, social political and economic components. There is hardly any fit-for all formulation of public policy as Lindbloom has aptly categorized it as a science of muddling through. In fact, policies are both temporally and contextually determined as one the proponents of policy sciences Harold D Lasswell has underscored it in his ‘contextual-configurative analysis’ as early as 1950s. Though, a lot of theoretical efforts have been made to make sense of this intricate dynamics of policy making, at the end of the day the applied area of public policy negates any such uniform, planned and systematic formulation. However, our policy makers seem to have learnt very little of that. Until recently, policy making was deemed as an absolutely specialized exercise to be conducted by a cadre of professionally trained seasoned mandarin. Attributes like homogeneity, impartiality, efficiency, and neutrality were considered as the watchwords of delivering common goods. Citizen or clientele was conceptualized as universal political or economic construct, to be taken care of uniformly. Moreover, policy makers usually have the proclivity to put anything into straightjacket, and to ignore the nuances therein. Hence, least attention has been given to the ground level reality, especially the socio-cultural milieu where the policy is supposed to be applied. Consequently, a substantial amount of public money goes in vain as the intended beneficiaries remain indifferent to the delivery of public policies. The present paper in the light of Reproductive Health Care policy in rural West Bengal has tried to underscore the criticality of socio-cultural factors in public health delivery. Indian health sector has traversed a long way. From a near non-existent at the time of independence, the Indian state has gradually built a country-wide network of health infrastructure. Yet it has to make a major breakthrough in terms of coverage and penetration of the health services in the rural areas. Several factors are held responsible for such state of things. These include lack of proper infrastructure, medicine, communication, ambulatory services, doctors, nursing services and trained birth attendants. Policy makers have underlined the importance of supply side in policy formulation and implementation. The successive policy documents concerning health delivery bear the testimony of it. The present paper seeks to interrogate the supply-side oriented explanations for the failure of the delivery of health services. Instead, it identified demand side to find out the answer. The state-led and bureaucratically engineered public health measures fail to engender demands as these measures mostly ignore socio-cultural nuances of health and well-being. Hence, the hiatus between supply side and demand side leads to huge wastage of revenue as health infrastructure, medicine and instruments remain unutilized in most cases. Therefore, taking proper cognizance of these factors could have streamlined the delivery of public health.

Keywords: context, policy, socio-cultural factor, uniformity

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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Authors: Genevieve R. Kan, Jolyon Ford

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Background: Caesarean section has become the routine route of delivery for breech fetuses, but breech cesarean deliveries are hypothesized to have poorer immediate neonatal outcomes when compared to cephalic deliveries. In accordance with this, in many Australian hospitals, the pediatric team is routinely required to attend every elective breech cesarean section in case urgent resuscitation is required. Our study aimed to determine whether term elective breech deliveries indeed had worse immediate neonatal outcomes at delivery, which will justify the necessity of pediatric staff presence at every elective breech cesarean delivery and influence the workload for the pediatric team. Objective: Elective breech cesarean deliveries were compared to elective cephalic cesarean deliveries at 37 weeks gestation or above to evaluate the immediate neonatal outcomes (Apgar scores <7 at 5 minutes, and Special Care Nursery admissions on Day 1 of life) of each group. Design: A retrospective cohort study Method: This study examined 2035 elective breech and cephalic singleton cesarean deliveries at term over 5 years from July 2017 to July 2022 at Frankston Hospital, a metropolitan hospital in Melbourne, Australia. There were 260 breech deliveries and 1775 cephalic deliveries. De-identified patient data were collected retrospectively from the hospital’s electronically integrated pregnancy and birth records to assess demographics and neonatal outcomes. Results: Apgar scores <7 at 5 minutes of life were worse in the breech group compared to the cephalic group (3.4% vs 1.6%). Special Care Nursery admissions on Day 1 of life were also higher for the breech cohort compared to the cephalic cohort (9.6% vs 8.7%). Conclusions: Our results support the expected findings that breech deliveries are associated with worse immediate neonatal outcomes. It, therefore, suggests that routine attendance at elective breech cesarean deliveries by the pediatric team is indeed required to assist with potentially higher needs for neonatal resuscitation and special care nursery admission.

Keywords: breech, cesarean section, Apgar scores, special care nursery admission

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Authors: V. Balamuralidhara

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The aim of the present work was to develop Paclitaxel loaded polyacrylamide grafted guar gum nanoparticles as pH responsive nanoparticle systems for targeting colon. The pH sensitive nanoparticles were prepared by modified ionotropic gelation technique. The prepared nanoparticles showed mean diameters in the range of 264±0.676 nm to 726±0.671nm, and a negative net charge 10.8 mV to 35.4mV. Fourier Transformed Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) studies suggested that there was no chemical interaction between drug and polymers. The encapsulation efficiency of the drug was found to be 40.92% to 48.14%. The suitability of the polyacrylamide grafted guar gum ERN’s for the release of Paclitaxel was studied by in vitro release at pH 1.2 and 7.4. It was observed that, there was no significant amount of drug release at gastric pH and 97.63% of drug release at pH 7.4 was obtained for optimized formulation F3 at the end of 12 hrs. In vivo drug targeting performance for the prepared optimized formulation (F3) and pure drug Paclitaxel was evaluated by HPLC. It was observed that the polyacrylamide grafted guar gum can be used to prepare nanoparticles for targeting the drug to the colon. The release performance was greatly affected by the materials used in ERN’s preparation, which allows maximum release at colon’s pH. It may be concluded that polyacrylamide grafted guar gum nanoparticles loaded with paclitaxel have desirable release responsive to specific pH. Hence it is a unique approach for colonic delivery of drug having appropriate site specificity and feasibility and controlled release of drug.

Keywords: colon targeting, polyacrylamide grafted guar gum nanoparticles, paclitaxel, nanoparticles

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: G. Ozturk, B. Demirci

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It is well known that essential oils used for therapeutic purposes for many years. In this study, five different Pharmacopoeia grade essential oils (Achillea millefolium L., Pimpinella anisum L., Matricaria recutita L., Eucalyptus globulus L., Salvia officinalis L.) which obtained from commercial sources were evaluated for chemical compositions, synergistic antimicrobial activities, and lipoxygenase enzyme inhibitions. Volatile components were determined by gas chromatography/flame ionization detector and gas chromatography/mass spectrometer, simultaneously. The potential antimicrobial activity of essential oils was tested against oral pathogenic standard strains such as Streptococcus mutans, Streptococcus sanguinis, Staphylococcus aureus, Corynebacterium striatum, Candida albicans and Candida krusei by broth microdilution methods. Ciprofloxacin and ketoconazole were used positive controls. It has been observed that the essential oils tested have average inhibitory antimicrobial activity against oral pathogens with a Minimum Inhibition Concentration of 20-0.625 mg/mL. The active essential oils have been combined with antibiotics and synergistic effects have been evaluated by Checkerboard method. ƩFIC values were determined. In combination with antibiotics M. recutita essential oil has been shown to have a synergistic effect against S. aureus in combination with tetracycline (ƩFIC 0.46). In addition, 5-LOX inhibitory activity was measured by modifying the spectrophotometric method developed by Baylac and Racine. As a result, 5-LOX % inhibition of S. officinalis, E. globulus and M. recutita were calculated as 34.0 ± 6.66, 72.7 ± 2.78 and 27.7 ± 0.60, respectively.

Keywords: antimicrobial activity, essential oils, synergistic activity, 5-lipoxygenase inhibition

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Authors: H. Noureddine, P. Rao, R. Guru, A. Chandratreya

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The nice guidance for elective total knee replacements states that patients should be given mechanical thrombo-prophylaxis, and if no contraindications chemical thromboprophylaxis in the form of Dabigatran etexilate, Rivaroxiban, UFH, LMWH, or Fondaparinux sodium (CG92, 1.5.14, January 2010). In Practice administering oral agents has been the dominant practice as it reduces the nursing needs, and shortens hospital stay and is generally received better by patients. However, there are well documented associated bleeding risks, and their effects are difficult to reverse in case of major bleeding. Our experience with oral factor 10 inhibitors used for thromboprophylaxis was marked with several patients developing complications necessitating return to the theatre for wound washouts. This has led us to try a different protocol for thromboprophylaxis that we applied on our patients undergoing total and unicondylar knee replacements. We applied mechanical thromboprophylaxis in the form of intermittent pneumatic pressure devices, and chemical thromboprophylaxis in the form of a dose of prophylactic LMWH pre-op, then 150 mg of Aspirin to start 24 hours after the surgery and to continue for 6 weeks, alongside GI cover with PPIs or antihistamines. We also administered local anaesthetics intra-operatively in line with the ERAS protocol thus encouraging early mobilization. We have identified a cohort of 133 patients who underwent one of the aforementioned procedures in the same trust, and by the same surgeon, where this protocol was applied and examined their medical notes retrospectively with a mean follow-up period of 14 months, to identify the rate and percentage of patients who had thrombo-embolic events in the post-operative period.

Keywords: aspirin, heparin, knee arthroplasty, thromboprophylaxis

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Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

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Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: Trieu Anh Ngoc, Nguyen Quang Kim

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Located at the downstream of the Mekong Delta, the Vietnamese Mekong Delta is well-known as 'rice bowl' of Vietnam. The Vietnamese Mekong Delta experiences widespread flooding annually where is habitat for about 17 million people. The economy of this region mainly depends on the agricultural productivities. The suspended sediment load in the Mekong River plays an important role in carrying contaminants and nutrients to the delta and changing the geomorphology of the delta river system. In many past decades, flooding and suspended sediment were considered as indispensable factors in agricultural cultivations. Although flooding in the wet season caused serious inundation in paddy field and affected livelihoods, it is an effective facility for flushing acid and saline to this area - alluvial soil heavily contaminated with acid and salt intrusion. In addition, sediment delivery to this delta contained rich-nutrients distributed and deposited on the fields through flooding process. In recent decades, the changing of flow and sediment transport have been strongly and clearly occurring due to upstream dam development and climate change. However, effects of sediment delivery on agricultural cultivations were less attention. This study investigated the impacts of upstream flow on sediment distribution in the Vietnamese Mekong Delta. Flow fluctuation and sediment distribution were simulated by the Mike 11 model, including hydrodynamics model and advection-dispersion model. Various scenarios were simulated based on anticipated upstream discharges. Our findings indicated that sediment delivery into the Vietnamese Mekong Delta come from not only Tien River but also border of Cambodia floodplains. Sediment distribution in the Vietnamese Mekong Delta is dramatically changed by the distance from the main rivers and the secondary channels. The dam development in the upstream is one of the major factors leading a decrease in sediment discharge as well as sediment deposition. Moreover, sea level rise partially contributed to decrease in sediment transport and change of sediment distribution between upstream and downstream of the Vietnamese Mekong Delta.

Keywords: sediment transport, sea level rise, climate change, Mike Model

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Authors: Angela Obose Oriazowanlan

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Despite the introduction of Entrepreneurship education into the Nigerian University curriculum to prepare graduates for self-employment roles in order to abate employment challenges, their unemployment rate still soars high. The study, therefore, examined the relevance of the curriculum contents and its delivery mechanism to equip graduates with appropriate entrepreneurial skills prior to graduation. Four research questions and two hypotheses guided the study. The survey research design was adopted for the study. An infinite population of graduates of a period of five years with 200 sample representatives using the simple random sampling technique was adopted. A 45-item structured questionnaire was used for data gathering. The gathered data thereof was anlysed using the descriptive statistics of mean and standard deviation, while the formulated hypotheses were tested with Z-score at 0.5 level of significance. The findings revealed, among others, that graduates acquisition of appropriate entrepreneurial skills for self-employment generation is low due to curriculum deficiencies, insufficient time allotment, and the delivery mechanism. It was recommended, among others, that the curriculum should be reviewed to improve its relevancy and that sufficient time should be allotted to enable adequate teaching and learning process.

Keywords: evaluation of entrepreneurship education (EE) curriculum, self-employment generation, graduates of tertiary institutions, Edo state, Nigeria

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Authors: Gudakesh Yadav

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Utter Pradesh, which is one of the largest states of India with unequal distribution of resources and different socioeconomic and cultural characteristics, level of different new born health care indicators varies a lot from one district to another district. State shared more than 21 percent of total live births of India; whereas, it accounts for 28 percent of total infant deaths of the country, with the 53 per thousand infant mortality rate. The present paper attempts to examine tempo-spatial changes in new born care practices during NFHS-1 to NFHS-3 and DLHS-2 to DLHS-3 in Uttar Pradesh and different regions. Descriptive statistics, rate-ratios, concentration index, multivariate and decomposition analysis has been used for the study. Findings of the study reveal that new born care practices have improved over the time in the state and across all the regions because of giving more emphasis on venerable groups like poor, rural, less educated mothers and scheduled caste & tribes but still it did not achieve the desired successes. Regional analysis of third rounds of DLHS shows that, coverage of intuitional delivery was the lowest in the central region. Performance of the southern region was the lowest in terms of initiation of breastfeeding, keeping baby warm and dry after the birth. The study calls for proper follow up of new born children to accelerate new born and child health care service and prioritises increasing antenatal check-ups and institutional delivery, which helps to improve level of other new born care services. At the policy level there is need to reach venerable groups like scheduled caste and tribes, poor and uneducated, and new mother especially in rural areas. High focused district should be allocated for better implementation of new born care promotion programme in low performing districts. Partnership with the private sector health professional is necessary to reach the every part of population.

Keywords: decomposition, inequality, initiation of breastfeeding, institutional delivery

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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The increasing use of nanomaterials in consumer and industrial products has aroused global concern regarding their fate in biological systems resulting in demand for parallel risk assessment. The objective of this study is investigating either the effect of individual or combined doses of idebenone, carnosine and vitamin E on amelioration of some biochemical indices of nano sized titanium dioxide (TiO2 NPS) induced metabolic disorders in mice liver. TiO2-NPS was administered in an oral dose of 150 mg/kg for consecutive 14 days followed by oral daily doses of the aforementioned antioxidants for 1 month. TiO2-NPS induced a significant elevation in serum level of ALT and AST, hepatic inflammatory markers (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover, mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation-2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down-regulation in the antiapoptotic factor (bcl2) level. In conclusion, idebenone, carnosine and vitamin E ameliorated the deviated parameters with a variable degree with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: idebenone, carnosine, vitamin E, TiO2 NPS, caspase-3, NrF2, NF-KB

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Authors: Bert H. Jacobson, Taylor Monaghan, John Sellers

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Intense resistance-type activity generally elicits delayed onset muscle soreness (DOMS) in individuals unaccustomed to such action. DOMS is a combination of contractile tissue microtrauma, osmotic pressure changes, alteration calcium regulation, and inflammation. Elevated muscle-specific enzyme creatine kinase (CK) is a marker of striated muscle damage. Avian immunoglobulin (IgY) mediates inflammation and may thereby reduce post-exercise DOMS. Purpose: The aim of this study was to compare the effect of oral IgY and placebo (Pl) on CK, serum relevels, and perceived pain following induced DOMS. Methods: Healthy college-aged females (N=16) were randomly divided into an experimental group (IgY) and a control group (PL). CK serum levels were recorded followed by 14 days of supplementation of either IgY or Pl at the following doses: days 1-2 =4.5 g, days 3-5 =9.0 g, and days 6-14 =13.5 g. Following the 14 d, lower limb DOMS was induced using two methods of resistance training. After 48 hours, subjects reported for a second blood draw. Results: One-way ANOVA resulted in the IgY group posting significantly less (p < 0.05) serum CK than the PL group. Furthermore, the IgY group experienced significantly less post-test perceived soreness than the Pl group. Conclusion: IgY supplementation lessens muscle CK levels and perceived muscle soreness following exercise, possibly due to an anti-inflammatory effect. It was suggested that IgY may serve as a buffer for DOMS thereby allowing the participant to continue vigorous exercise without discomfort.

Keywords: muscle, soreness, damage, serum

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Authors: Anandita Mitro, Archana Srivastava, Bidisha Banerjee

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The present paper attempts to analyze the hierarchy and interconnection of factors responsible for the uptake of BCG vaccination in India. The study uses National Family Health Survey (NFHS-5) data which was conducted during 2019-21. The univariate logistic regression method is used to understand the univariate effects while the interconnection effects have been studied using the Categorical Inference Tree (CIT) which is a non-parametric Machine Learning (ML) model. The hierarchy of the factors is further established using Conditional Inference Forest which is an extension of the CIT approach. The results suggest that BCG vaccination coverage was influenced more by system-level factors and awareness than education or socio-economic status. Factors such as place of delivery, antenatal care, and postnatal care were crucial, with variations based on delivery location. Region-specific differences were also observed which could be explained by the factors. Awareness of the disease was less impactful along with the factor of wealth and urban or rural residence, although awareness did appear to substitute for inadequate ANC. Thus, from the policy point of view, it is revealed that certain subpopulations have less prevalence of vaccination which implies that there is a need for population-specific policy action to achieve a hundred percent coverage.

Keywords: vaccination, NFHS, machine learning, public health

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Jiwon Lee, Si-hwan Jang, Sanghyun Joo

Abstract:

The popularity of emoticons are on the rise since the mobile messengers are generalized. At the same time, few problems of emoticons are also occurred due to innate characteristics of emoticons. Too many emoticons make difficult people to select one which is well-suited for user's intention. On the contrary to this, sometimes user cannot find the emoticon which expresses user's exact intention. Poor information delivery of emoticon is another problem due to a major part of current emoticons are focused on emotion delivery. In this situation, we propose a new concept of emoticons, editable emoticons, to solve above drawbacks of emoticons. User can edit the components inside the proposed editable emoticon and send it to express his exact intention. By doing so, the number of editable emoticons can be maintained reasonable, and it can express user's exact intention. Further, editable emoticons can be used as information deliverer according to user's intention and editing skills. In this paper, we propose the concept of editable emoticons and schema based editable emoticon description method. The proposed description method is 200 times superior to the compared screen capturing method in the view of transmission bandwidth. Further, the description method is designed to have compatibility since it follows MPEG-UD international standard. The proposed editable emoticons can be exploited not only mobile applications, but also various fields such as education and medical field.

Keywords: description schema, editable emoticon, emoticon transmission, mobile applications

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Authors: K. Kalaiarasan, B. Pandeeswari, A. Arockia John Francis

Abstract:

Wireless, Multi-hop networks consist of one or more intermediate nodes along the path that receive and forward packets via wireless links. The backpressure algorithm provides throughput optimal routing and scheduling decisions for multi-hop networks with dynamic traffic. Xpress, a cross-layer backpressure architecture was designed to reach the capacity of wireless multi-hop networks and it provides well coordination between layers of network by turning a mesh network into a wireless switch. Transmission over the network is scheduled using a throughput-optimal backpressure algorithm. But this architecture operates much below their capacity due to out-of-order packet delivery and variable packet size. In this paper, we present Xpress-T, a throughput optimal backpressure architecture with TCP support designed to reach maximum throughput of wireless multi-hop networks. Xpress-T operates at the IP layer, and therefore any transport protocol, including TCP, can run on top of Xpress-T. The proposed design not only avoids bottlenecks but also handles out-of-order packet delivery and variable packet size, optimally load-balances traffic across them when needed, improving fairness among competing flows. Our simulation results shows that Xpress-T gives 65% more throughput than Xpress.

Keywords: backpressure scheduling and routing, TCP, congestion control, wireless multihop network

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Authors: Jinfeng Zhang, Chun-Sing Lee

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The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

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Authors: Mimoza Canga, Irene Malagnino, Vergjini Mulo, Alketa Qafmolla, Vito Antonio Malagnino

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Background: Dental caries is the most common dental disease and pregnancy represents a special process of physical, hormonal and metabolic changes in pregnant women, which is accompanied by an imbalance in the oral cavity. Objective: The objective of this study is to evaluate caries reduction after dental visits, the scaling of teeth, fluoridated water, brushing of the teeth and using fluoride toothpaste before and during pregnancy. Materials and methods: This study was conducted in the time period March 2018- September 2021, the age range of the participants was: 18-41 years old. The sample taken under observation was composed of 84 pregnant women. The questionnaire included the demographic characteristics of the sample, such as age, women's education level was primary, secondary, and higher education. Based on women's education level, our analysis found that 25.9% of pregnant women had completed primary education, 35.2% of them had secondary education and 38.9% of pregnant women had higher education. The descriptive and analytical research analysis is formulated as a longitudinal study. Statistical analysis was performed using IBM SPSS Statistics 23.0. The significance level (α) was set at 0.05, whereas P-value and analysis of variance (ANOVA) were used to analyze the data. Results: In the present study, it was observed that there is a strong relationship between dental visits and the scaling of the teeth with the value of P˂ .0001. While the number of teeth with caries before pregnancy and fluoridated water have a P-value=0.002. If we compare the same factor with the number of teeth with dental caries during pregnancy, the correlation is P-value = 0.0001. The number of teeth with caries before pregnancy and carbohydrates consumption has a strong relation with P-value=0.05. According to the present research, the number of teeth with dental caries before pregnancy in relation to brushing the teeth has a P-value ˂ 0.05. Furthermore, in the actual research, it was established that using fluoride toothpaste doesn’t affect the number of teeth with caries before pregnancy with a P-value= .314. Conclusion: According to the results of the present study performed in Albania, it was found out that the periodical dental visits, scaling of the teeth, fluoridated water, brushing of the teeth influenced caries reduction before and during pregnancy. In comparison, the usage of fluoride toothpaste did not have any effect on dental caries reduction in the same time period. The recommendations are as follows: maintaining oral hygiene, using fluoridated water and brushing the teeth regularly. Healthcare providers should inform pregnant women about the importance of oral health and the implementation of measures to manage dental caries.

Keywords: brushing of the teeth, dental visits, dental scaling, fluoridated water, pregnancy

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Authors: Evelyn Osehontue Uroro, Richard Bright, Jing Yang Quek, Krasimir Vasilev

Abstract:

Bacterial infections have been a challenge both in the public and private sectors. The colonization of bacteria often occurs in medical devices such as catheters, heart valves, respirators, and orthopaedic implants. When biomedical devices are inserted into patients, the deposition of macromolecules such as fibrinogen and immunoglobin on their surfaces makes it easier for them to be prone to bacteria colonization leading to the formation of biofilms. The formation of biofilms on medical devices has led to a series of device-related infections which are usually difficult to eradicate and sometimes cause the death of patients. These infections require surgical replacements along with prolonged antibiotic therapy, which would incur additional health costs. It is, therefore, necessary to prevent device-related infections by inhibiting the formation of biofilms using intelligent technology. Antibiotic resistance of bacteria is also a major threat due to overuse. Different antimicrobial agents have been applied to microbial infections. They include conventional antibiotics like rifampicin. The use of conventional antibiotics like rifampicin has raised concerns as some have been found to have hepatic and nephrotoxic effects due to overuse. Hence, there is also a need for proper delivery of these antibiotics. Different techniques have been developed to encapsulate and slowly release antimicrobial agents, thus reducing host cytotoxicity. Examples of delivery systems are solid lipid nanoparticles, hydrogels, micelles, and polymeric nanoparticles. The different ways by which drugs are released from polymeric nanoparticles include diffusion-based release, elution-based release, and chemical/stimuli-responsive release. Polymeric nanoparticles have gained a lot of research interest as they are basically made from biodegradable polymers. An example of such a biodegradable polymer is polycaprolactone (PCL). PCL degrades slowly by hydrolysis but is often sensitive and responsive to stimuli like enzymes to release encapsulants for antimicrobial therapy. This study presents the synthesis of PCL nanoparticles loaded with rifampicin and the on-demand release of rifampicin for treating staphylococcus aureus infections.

Keywords: enzyme, Staphylococcus aureus, PCL, rifampicin

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Authors: G. Salavwa, P. Erhijakpor Jr., H. Ukwu

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This study will explore child labour issues in Nigeria because it is capable of affecting the physical and general well-being of children who perform hazardous work. This feat will be achieved through qualitative research methodology. Data collection shall be elicited by oral interviews and documental content analysis to delve on the application of the Convention on the Rights of the Child (CRC), International Labour Organization ILO and Geneva Convention relating to child labour practices in Nigeria. This will include the relevance of present domestic laws relating to child labour as implemented in Nigeria, together with factors that contribute to the practice of child labour in the country. The oral interview data analysis will be performed by breaking the interview data into significant statements and themes. This shall be done by comparing and determining the commonalities that are prevalent in the participants’ views regarding child labour menace in Nigeria. Presumably, findings from this study shall unveil that a poor educational policy, a widespread poverty level which is mostly prevalent amongst families in the rural areas of the country, a lack of employment for adults, have led to the ineffectiveness of the local child labour laws in Nigeria. These has in turn culminated into a somewhat non-implementation of the international laws of the CRC, ILO and Geneva Declaration on child labour to which the Nigerian government is a signatory. Based on the finding, this study will calls on the government of Nigeria to extend its free educational policy from the elementary, secondary to tertiary educations. The government also has to ensure that offenders of children’s rights should face a severe punishment.

Keywords: commonalities, tertiary, constitution, qualitative

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Authors: F. O. Adeosun, I. O. Orubuloye, O. O. Babalola

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Although caesarean section has greatly improved obstetric care throughout the world, in developing countries there is a great aversion to caesarean section. This study was carried out to examine the rate at which pregnant women with pre-eclampsia choose caesarean section over natural birth. A cross-sectional study was conducted among 500 pre-eclampsia antenatal clients seen at the States University Teaching Hospitals in the last one year. The sample selection was purposive. Information on their educational background, beliefs and attitudes were collected. Data analysis was presented using simple percentages. Out of 500 women studied, 38% favored caesarean section while 62% were against it. About 89% of them understood what caesarean section is, 57.3% of those who understood what caesarean section is will still not choose it as an option. Over 85% of the women believed caesarean section is done for medical reasons. If caesarean section is given as an option for childbirth, 38% would go for it, 29% would try religious intervention, 5.5% would not choose it because of fear, while 27.5% would reject it because they believe it is culturally wrong. Majority of respondents (85%) who favored caesarean delivery are aware of the risk attached to choosing virginal birth but go an extra mile in sourcing funds for a caesarean session while over 64% cannot afford the cost of caesarean delivery. It is therefore pertinent to encourage research in prediction methods and prevention of occurrence, since this would assist patients to plan on how to finance treatment.

Keywords: caesarean section, choice, cost, pre eclampsia, prediction methods

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Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

Abstract:

Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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Authors: Joseph Carl Macalintal, Erlinda Armovit

Abstract:

Magnesium sulfate has been a mainstay in the management of preeclampsia and is associated with a decreased incidence of morbidity and mortality. The syndrome has an unpredictable course, sometimes rapidly evolving to full-blown disease. In patients with deteriorating status, it is indicated to terminate the pregnancy via cesarean section. The anesthesiologists would prefer to have the procedure done under regional anesthesia; however, there may be cases when neuraxial anesthesia is contraindicated, or a general anesthesia would permit prompt delivery of the fetus. A patient with severe preeclampsia was given magnesium sulfate intrapartum, wherein a primary cesarean section was indicated for arrest in cervical dilatation, and was performed under general anesthesia. The patient developed acute respiratory failure and the causes of this occurrence were investigated in this report. It was later found out that neither the hypermagnesemia nor the muscle relaxant alone caused the patient’s condition but the interaction between the two. The patient was managed expectantly at the intensive care unit (ICU) and was eventually extubated during the 1st post-operative day. Knowledge of this drug interaction would allow obstetricians to advise their patients and their family about the possibility of prolonged intubation and ICU admission. This would also bring to the anesthesiologists’ attention the need to decrease the dose of muscle relaxant and to prepare drugs for immediate decurarisation.

Keywords: eclampsia, magnesium sulfate, preeclampsia, rocuronium bromide

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Authors: Ma. Eliza Jijeth V. dela Cruz

Abstract:

Technology is a recent prodigy in people’s everyday life that has taken off. It infiltrated almost every aspect of one’s lives, changing how people work, how people learn and how people perceive things. Academic Institutions, just like other organizations, have deeply modified its strategies to integrate technology into the institutional vision and corporate strategy that has never been greater. Information and Communications Technology (ICT) continues to be recognized as a major factor in organizations realizing its aims and objectives. Consequently, ICT has an important role in the mobilization of an academic institution’s strategy to support the delivery of operational, strategic or transformational objectives. This ICT strategy should align the institution with the radical changes of the ICT world through the use of Enterprise Architecture (EA). Hence, EA’s objective is to optimize the islands of legacy processes to be integrated that is receptive to change and supportive of the delivery of the strategy. In this paper, the focus is to explore the motivational antecedents during the adoption of EA in a Higher Education Institution in the Philippines for its ICT strategic plan. The seven antecedents (viewpoint, stakeholders, human traits, vision, revolutionary innovation, techniques and change components) provide understanding into EA adoption and the antecedents that influences the process of EA adoption.

Keywords: Enterprise Architecture, Adoption, Antecedents, Higher Educational Institutions

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Authors: Janis Zarins, Kristaps Blums, Oskars Radzins, Renars Deksnis, Atis Svare, Santa Salaka

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Wide tumor resection remains the first choice method for tumors of the oral cavity. Nevertheless, remained tissue defect impacts patients functional and aesthetical outcome, which could be improved using microvascular tissue transfers. Mandibular reconstruction is challenging due to the complexity of composite tissue defects and occlusal relationships for normal eating, chewing, and pain free jaw motions. Individual 3-D virtual planning would provide better symmetry and functional outcome. The main goal of preoperative planning is to develop a customized surgical approach with patient specific cutting guides of the mandible, osteotomy guides of the fibula, pre-bended osteosynthesis plates to perform more precise reconstruction, to decrease the surgery time and reach the best outcome. Our study is based on the analysis of 32 patients operated on between 2019 to 2021. All patients underwent mandible reconstruction with vascularized fibula flaps. Patients characteristics, surgery profile, survival, functional outcome, and quality of life was evaluated. Preoperative planning provided a significant decrease of surgery time and the best arrangement of bone closely similar as before the surgery. In cases of bone asymmetry, deformity and malposition, a new mandible was created using 3D planning to restore the appearance of lower jaw anatomy and functionality.

Keywords: mandibular, 3D planning, cutting guides, fibula flap, reconstruction

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