Search results for: slow drug release

Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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Authors: Nawras Kurzom, Avi Mendelsohn

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The effects of background music on learning and memory are inconsistent, partly due to the intrinsic complexity and variety of music and partly to individual differences in music perception and preference. A prominent musical feature that is known to elicit strong emotional responses is musical tension. Musical tension can be brought about by building anticipation of rhythm, harmony, melody, and dynamics. Delaying the resolution of dominant-to-tonic chord progressions, as well as using dissonant harmonics, can elicit feelings of tension, which can, in turn, affect memory formation of concomitant information. The aim of the presented studies was to explore how forming declarative memory is influenced by musical tension, brought about within continuous music as well as in the form of isolated chords with varying degrees of dissonance/consonance. The effects of musical tension on long-term memory of declarative information were studied in two ways: 1) by evoking tension within continuous music pieces by delaying the release of harmonic progressions from dominant to tonic chords, and 2) by using isolated single complex chords with various degrees of dissonance/roughness. Musical tension was validated through subjective reports of tension, as well as physiological measurements of skin conductance response (SCR) and pupil dilation responses to the chords. In addition, music information retrieval (MIR) was used to quantify musical properties associated with tension and its release. Each experiment included an encoding phase, wherein individuals studied stimuli (words or images) with different musical conditions. Memory for the studied stimuli was tested 24 hours later via recognition tasks. In three separate experiments, we found positive relationships between tension perception and physiological measurements of SCR and pupil dilation. As for memory performance, we found that background music, in general, led to superior memory performance as compared to silence. We detected a trade-off effect between tension perception and memory, such that individuals who perceived musical tension as such displayed reduced memory performance for images encoded during musical tension, whereas tense music benefited memory for those who were less sensitive to the perception of musical tension. Musical tension exerts complex interactions with perception, emotional responses, and cognitive performance on individuals with and without musical training. Delineating the conditions and mechanisms that underlie the interactions between musical tension and memory can benefit our understanding of musical perception at large and the diverse effects that music has on ongoing processing of declarative information.

Keywords: musical tension, declarative memory, learning and memory, musical perception

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Authors: Samantha Jeffries, Chontit Chuenurah

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Thailand incarcerates the largest number of women and has the highest female incarceration rate in South East Asia. Since the 1990s, there has been a substantial increase in the number, rate and proportion of women imprisoned. Thailand places a high priority on the gender specific contexts out of which offending arises and the different needs of women in the criminal justice system. This is manifested in work undertaken to guide the development of the United Nations Rules for the Treatment of Women Prisoners and Non-Custodial Measures for Women Offenders (the Bangkok Rules); adopted by the United Nations General Assembly in 2010. The Bangkok Rules make a strong statement about Thailand’s recognition of and commitment to the fair and equitable treatment of women throughout their contact with the criminal justice system including at sentencing and in prison. This makes the comparatively high use of imprisonment for women in Thailand particularly concerning and raises questions about the relationship between gender, crime and criminal justice. While there is an extensive body of research in Western jurisdictions exploring women’s pathways to prison, there is a relative dearth of methodologically robust research examining the possible gendered circumstances leading to imprisonment in Thailand. In this presentation, we will report preliminary findings from a qualitative study of women’s pathways to prison in Thailand. Our research aims were to ascertain: 1) the type, frequency, and context of criminal behavior that led to women’s incarceration, 2) women’s experiences of the criminal justice system, 3) the broader life experiences and circumstances that led women to prison in Thailand. In-depth life history interviews (n=77) were utilized to gain a comprehensive understanding of women’s journeys into prison. The interview schedule was open-ended consisting of prisoner responses to broad discussion topics. This approach provided women with the opportunity to describe significant experiences in their lives, to bring together distinct chronologies of events, and to analyze links between their varied life experiences, offending, and incarceration. Analyses showed that women’s journey’s to prison take one of eight pathways which tentatively labelled as follows, the: 1) harmed and harming pathway, 2) domestic/family violence victimization pathway, 3) drug connected pathway, 4) street woman pathway, 5) economically motivated pathway, 6) jealousy anger and/or revenge pathway, 7) naivety pathway, 8) unjust and/or corrupted criminal justice pathway. Each will be fully discussed during the presentation. This research is significant because it is the first in-depth methodologically robust exploration of women’s journeys to prison in Thailand and one of a few studies to explore gendered pathways outside of western contexts. Understanding women’s pathways into Thailand’s prisons is crucial to the development of effective planning, policy and program responses not only while women are in prison but also post-release. To best meet women’s needs in prison and effectively support their reintegration, we must have a comprehensive understanding of who these women are, what offenses they commit, the reasons that trigger their confrontations with the criminal justice system and the impact of the criminal justice system on them.

Keywords: pathways, prison, women, Thailand

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Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

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The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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Authors: Kyungsuk Cho, H. Y. Kim, S. U. Chae, J. H. Choi

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Technological development has led to the construction of super-tall buildings and insulators are increasingly used as exterior finishing materials to save energy. However, insulators are usually combustible and vulnerable to fire. Fires like that at Wooshin Golden Suite Building in Busan, Korea in 2010 and that at CCTV Building in Beijing, China are the major examples of fire spread accelerated by combustible insulators. The exterior finishing materials of a high-rise building are not made of insulators only, but they are integrated with the building’s external cladding system. There is a limit in evaluating the fire safety of a cladding system with a single small-unit material such as a cone calorimeter. Therefore, countries provide codes to evaluate the fire safety of exterior finishing materials using full-scale tests. This study compares and to examine the applicability of the methods to Korea. Standard analysis showed differences in the type and size of fire sources and duration and exterior finishing materials also differed in size. In order to confirm the differences, fire tests were conducted on identical external cladding systems to compare fire safety. Although the exterior finishing materials were identical, varying degrees of fire spread were observed, which could be considered as differences in the type and size of the fire sources and duration. Therefore, it is deduced that extended studies should be conducted before the evaluation methods and standards are employed in Korea. The two standards for evaluating fire safety provided different results. Peak heat release rate was 5.5MW in ISO method and 3.0±0.5MW in BS method. Peak heat release rate in ISO method continued for 15 minutes. Fire ignition, growth, full development and decay evolved for 30 minutes in BS method where wood cribs were used as fire sources. Therefore, follow-up studies should be conducted to determine which of the two standards provides fire sources that approximate the size of flames coming out from the openings or those spreading to the outside when a fire occurs at a high-rise building.

Keywords: external cladding systems, fire safety evaluation, ISO 13785-2, BS 8414

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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Authors: Aly Kassem, Eman Sapet, Eman Abdelbaset, Hosam Mahmoud

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Objective: Hypertension is an important public health challenge being one of the most common worldwide disease-affecting human. Our aim is to study the clinical characteristics, therapeutic regimens, treatment compliance, and risk factors in a sector of of hypertensive patients at Sohag City. Subject and Methods: A cross sectional study; conducted in Sohag city; it involved 520 patients; males (45.7 %) and females (54.3 %). Their ages ranged between 35-85 years. BP measurements, BMI, blood glucose, Serum creatinine, urine analysis, serum Lipids, blood picture and ECG were done all the studied patients. Results: Hypertension presented more between non-smokers (72.55%), females (54.3%), educated patients (50.99%) and patients with low SES (54.9%). CAD presented in (51.63%) of patients, while laboratory investigations showed hyperglycaemia in (28.7%), anemia in (18.3%), high serum creatinine level in (8.49%) and proteinuria in (10.45%) of patient. Adequate BP control was achieved in (49.67%); older patients had lower adequacy of BP control in spite of the extensive use of multiple-drug therapy. Most hypertensive patients had more than one coexistent CV risk factor. Aging, being a female (54.3%), DM (32.3%), family history of hypertension (28.7%), family history of CAD (25.4%), and obesity (10%) were the common contributing risk factors. ACE-inhibitors were prescribed in (58.16%), Beta-blockers in (34.64%) of the patients. Monotherapy was prescribed for (41.17%) of the patients. (75.81%) of patients had regular use of their drug regimens. (49.67%) only of patients had their condition under control, the number of drugs was inversely related to BP control. Conclusion: Hypertensive patients in Sohag city had a profile of high CV risks, and poor blood pressure control particularly in the elderly. A multidisciplinary approach for routine clinical check-up, follow-up, physicians and patients training, prescribing simple once-daily regimens and encouraging life style modifications are recommended. Anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance.

Keywords: anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance

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Authors: Yang, Min-chih, Shih-Jen Feng, Bo-Tsang Li

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The concept of “Brownfield” has been developed for nearly 35 years since it was put forward in 《Comprehensive Environmental Response, Compensation, and Liability Act, CERCLA》of USA in 1980 for solving the problem of soil contamination of those old industrial lands, and later, many countries have put forward relevant policies and researches continuously. But the related concept in Taiwan, a country has developed its industry for 60 years, is still in its infancy. This leads to the slow development of Brownfield related research and policy in Taiwan. When it comes to build the foundation of Brownfield development, we have to depend on the related experience and research of other countries. They are four aspects about Brownfield: 1. Contaminated Land; 2. Derelict Land; 3. Vacant Land; 4. Previously Development Land. This study will focus on and deeply investigate the Vacant land and contaminated land.

Keywords: brownfield, industrial land, redevelopment, assessment index

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Authors: Razyeh Behbahani, Martin L. Plumer, Ivan Saika-Voivod

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Micromagnetic simulations based on the stochastic Landau-Lifshitz-Gilbert equation are used to calculate dynamic magnetic hysteresis loops relevant to magnetic hyperthermia applications. With the goal to effectively simulate room-temperature loops for large iron-oxide based systems at relatively slow sweep rates on the order of 1 Oe/ns or less, a coarse-graining scheme is proposed and tested. The scheme is derived from a previously developed renormalization-group approach. Loops associated with nanorods, used as building blocks for larger nanoparticles that were employed in preclinical trials (Dennis et al., 2009 Nanotechnology 20 395103), serve as the model test system. The scaling algorithm is shown to produce nearly identical loops over several decades in the model grain sizes. Sweep-rate scaling involving the damping constant alpha is also demonstrated.

Keywords: coarse-graining, hyperthermia, hysteresis loops, micromagnetic simulations

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: A. Argiri, A. Molla, Tzouvalekas, E. Skoufogianni, N. Danalatos

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The release of heavy metals into the environment has increased over the last years. In this study, 25 soil samples (0-15 cm) from the fields near the mining area in Drama region were selected. The samples were analyzed in the laboratory for their physicochemical properties and for seven “pseudo-total’’ heavy metals content, namely Pb, Zn, Cd, Cr, Cu, Ni, and Mn. The total metal concentrations (Pb, Zn, Cd, Cr, Cu, Ni and Mn) in digests were determined by using the atomic absorption spectrophotometer. According to the results, the mean concentration of the listed heavy metals in 25 soil samples are Cd 1.1 mg/kg, Cr 15 mg/kg, Cu 21.7 mg/kg, Ni 30.1 mg/kg, Pd 50.8 mg/kg, Zn 99.5 mg/kg and Mn 815.3 mg/kg. The results show that the heavy metals remain in the soil even if the mining closed many years ago.

Keywords: Greece, heavy metals, mining, pollution

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

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The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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Authors: Syeda Azeem Unnisa

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The present study was undertaken at Jawaharnagar Solid Waste Municipal Dumpsite, Greater Hyderabad Municipal Corporation, Telangana State, India in 2017 which generates 90,000 litres of leachate per day. The main objective of the leachate treatment was to remove organic compounds like color, suspended solids, ammonia and COD by coagulation-flocculation using polyaluminum chloride (PAC) as coagulant which has higher coagulant efficiency and relative low cost compared to the conventional coagulants. Jar test apparatus was used to conduct experiments for pH 7, rapid mixing speed 150 rpm for 3 minute, slow mixing speed 30 rpm for 20 minute and the settling time of 30 minute for different dosage of PAC (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 and 5.0 g/L). The highest percentage of removal of suspended solids, color, COD and ammonical nitrogen are 97%, 96%, 60% and 37% with PAC optimum dose of 2.0 g/l. The results indicate that the PAC was effective in leachate treatment which is very much suitable for high toxicity of waste and economically feasible for Indian conditions. The treated water can be utilized for other purpose apart from drinking.

Keywords: coagulant, leachate, polyaluminium chloride, treatment

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Authors: Anne-Loes K. Warps, Rob A. E. M. Tollenaar, Pieter J. Tanis, Jan Willem T. Dekker

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Anastomotic leakage after colorectal cancer surgery remains a severe complication. Early diagnosis and treatment are essential to prevent further adverse outcomes. In the literature, it has been suggested that earlier reintervention is associated with better survival, but anastomotic leakage can occur with a highly variable time interval to index surgery. This study aims to evaluate the time-interval between rectal cancer resection with primary anastomosis creation and reoperation, in relation to short-term outcomes, stratified for the use of a defunctioning stoma. Methods: Data of all primary rectal cancer patients that underwent elective resection with primary anastomosis during 2013-2019 were extracted from the Dutch ColoRectal Audit. Analyses were stratified for defunctioning stoma. Anastomotic leakage was defined as a defect of the intestinal wall or abscess at the site of the colorectal anastomosis for which a reintervention was required within 30 days. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay and readmission. The association between time to reoperation and outcome was evaluated in three ways: Per 2 days, before versus on or after postoperative day 5 and during primary versus readmission. Results: In total 10,772 rectal cancer patients underwent resection with primary anastomosis. A defunctioning stoma was made in 46.6% of patients. These patients had a lower anastomotic leakage rate (8.2% vs. 11.6%, p < 0.001) and less often underwent a reoperation (45.3% vs. 88.7%, p < 0.001). Early reoperations (< 5 days) had the highest complication and mortality rate. Thereafter the distribution of adverse outcomes was more spread over the 30-day postoperative period for patients with a defunctioning stoma. Median time-interval from primary resection to reoperation for defunctioning stoma patients was 7 days (IQR 4-14) versus 5 days (IQR 3-13 days) for no-defunctioning stoma patients. The mortality rate after primary resection and reoperation were comparable (resp. for defunctioning vs. no-defunctioning stoma 1.0% vs. 0.7%, P=0.106 and 5.0% vs. 2.3%, P=0.107). Conclusion: This study demonstrated that early reinterventions after anastomotic leakage are associated with worse outcomes (i.e. mortality). Maybe the combination of a physiological dip in the cellular immune response and release of cytokines following surgery, as well as a release of endotoxins caused by the bacteremia originating from the leakage, leads to a more profound sepsis. Another explanation might be that early leaks are not contained to the pelvis, leading to a more profound sepsis requiring early reoperations. Leakage with or without defunctioning stoma resulted in a different type of reinterventions and time-interval between surgery and reoperation.

Keywords: rectal cancer surgery, defunctioning stoma, anastomotic leakage, time-interval to reoperation

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and Public Health Significance of Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Socio-demographic data and Public Health Significance were collected using a predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using an ice box to Mekelle University, College of Veterinary Sciences, for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by the disc diffusion method. Data obtained were cleaned and entered into STATA 22.0 and a logistic regression model with odds ratio was calculated to assess the association of risk factors with bacterial contamination. A P-value < 0.05 was considered statistically significant. Results: In the present study, 88 out of 250 (35.2%) were found to be contaminated with Staphylococcus aureus. Among the raw meat specimens, the positivity rate of Staphylococcus aureus was 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risks, factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35 3.35) was found to be statistically significant and have associated with Staphylococcus aureus contamination. All isolates of thirty-seven of Staphylococcus aureus were checked and displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. Whereas the showed resistance to cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aureus isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin, whereas they showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi-drug resistance pattern for Staphylococcus aureus was 90% and 100% of butchery and abattoir houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the development of hand washing behavior and availability of safe water in the butchery houses to reduce the burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics.

Keywords: abattoir house, AMR, butchery house, S. aureus

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Authors: Sadhana Sharma, Neha Sharma, Hardik Khandelwal, Arti Sharma

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Background: It is widely acknowledged globally that parents must advocate for their children's drug and substance abuse prevention. However, many parents find it difficult to advocate due to systemic and logistical barriers. Alternatives to introducing advocacy, awareness, and support for the prevention of drug and substance abuse to children could occur in schools. However, little research has been conducted on the development of advocates for substance abuse in school settings. Objective: to evaluate the effectiveness of a school-based addiction prevention and control created as part of the Rajasthan Addiction Prevention Project (a partnership between state-community initiative). Methods: We conducted an evaluation in this study to determine the impact of a RAPP on a primary outcome (substance abuse knowledge) and other outcomes (family–school partnership, empowerment, and support). Specifically, between September-December 2022, two schools participated in the intervention group (advocacy training), and two schools participated in the control group (waiting list). The RAPP designed specialised 2-hrs training to equip teachers-parents with the knowledge and skills necessary to advocate for their own children and those of other families. All participants were required to complete a pre- and post-survey. Results: The intervention group established school advocates in schools where trained parents volunteered to lead support groups for high-risk children. Compared to the participants in the wait list control group, those in the intervention group demonstrated greater education knowledge, P = 0.002, and self-mastery, P = 0.04, and decreased family–school partnership quality, P = 0.002.Conclusions: The experimental evaluation of school-based advocacy programme revealed positive effects on substance abuse that persist over time. The approach wa s deemed feasible and acceptable by both parents and the school.

Keywords: prevention, school based, addiction, advocacy

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Authors: Mohammad Ranjbar, Mohammad Bazyar, Blake Angell, Thomas Lung, Yibeltal Assefa

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Background: Current health insurance programs in Iran suffer from low enrolment and are not sufficient to attain the country to universal health coverage (UHC). We hypothesize that improving the enrollment rate and moving towards a more sustainable UHC can be achieved by improving the benefits package and providing new incentives. The objective of this study is to assess public preferences and willingness to pay (WTP) for social health insurance (SHI) in Iran. Methods: A discrete choice experiment (DCE) was conducted in 2021, using a self-administered questionnaire on 500 participants to estimate WTP and determine individual preferences for the SHI in Yazd, Iran. Respondents were presented with an eight-choice set and asked to select their preferred one. In each choice set, scenarios were described by eight attributes with varying levels. The conditional logit regression model was used to analyze the participants' preferences. Willingness to pay for each attribute was also calculated. Results: Most included attributes were significant predictors of the choice of a health insurance package. The maximum coverage of hospitalization costs in the private sector, ancillary services such as glasses, canes, etc., as well as coverage for hospitalization costs in the public sector and drug costs, were the most important determining factors for this choice. Coverage of preventive dental care did not significantly influence respondent choices. Estimating WTP showed that individuals are willing to pay more for higher financial protection, particularly against private sector costs; the WTP to increase the coverage of hospitalization costs in the private sector from 50% to 90% is estimated at 362,068 IR, Rials per month. Conclusion: This study identifies the key factors that the population value with regard to health insurance and the tradeoffs they are willing to make between them. Hospitalization, drugs, and ancillary services were the most important determining factors for their choice. The data suggest that additional resources coming into the Iranian health system might best be prioritized to cover hospitalization and drug costs and those associated with ancillary services.

Keywords: social health insurance, preferences, discrete choice experiment, willingness to pay

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Authors: P. F. Wong, H. Salleh, F. A. Rahim

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The adoption of building information modeling (BIM) is increasing in the construction industry. However, quantity surveyors are slow in adoption compared to other professions due to lack of awareness of the BIM’s potential in their profession. It is still unclear on how BIM application can enhance quantity surveyors’ work performance and project performance. The aim of this research is to identify the capabilities of BIM in quantity surveying practices and examine the relationship between BIM capabilities and project performance. Questionnaire survey and interviews were adopted for data collection. Literature reviews identified there are eleven BIM capabilities in quantity surveying practice. Questionnaire results showed that there are several BIM capabilities significantly correlated with project performance in time, cost and quality aspects and the results were validated through interviews. These findings show that BIM has the capabilities to enhance quantity surveyors’ performances and subsequently improved project performance.

Keywords: Building Information Modeling (BIM), quantity surveyors, capability, project performance

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Authors: A. Al-Yaqout, A. Al-Alawi, T. Al-Said, E. Al-Enezi, M. Al-Roumi

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Kuwait’s marine environment suffers from increased organic pollution. Sea cucumbers play an important role in the marine environment. They create a healthier environment for many types of benthic micro-organisms through their slow movement and feeding mechanism on micro-organisms and organic material. A preliminary study has been conducted in Kuwait Institute for Scientific Research to assess the possibility of using sea cucumbers for mitigation of the coastal pollution. Sediments were collected from locations identified to be heavily loaded with organic pollutants. Ten aquaria glass tanks, 65x 40x 30cm will be supplied with 10 cm height (14 kg) of the sediments added in each tank and filled with 70 L of filtered seawater. Two species were used in this study, Stichopus hermanni, and Holothuria atra. Water and sediment samples were analyzed weekly. The results showed promising possibility for using sea cucumber to lower the organic load in sediments.

Keywords: organic pollution, sea cucumbers, mitigation, Stichopus hermanni, Holothuria atra

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Authors: Noshaba Dilbar, Hina Ashraf

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Medicinal plants are considered as rich source of ingredients which can be used in drug development and synthesis. Moreover, these plants play a vital role in the development of human culture of using ayurvedic medicines around the whole world. Among all plants, dessert plants are being proved as effective source of ayurvedic medicines and remedy against many diseases. Considering the fact, two plant species Limium indicum and Euphorbia granulata were taken from Cholistan dessert of Bahawalpur, Pakistan. Firstly, phytochemical screening was done by making dry and fresh plant extracts in five different solvents i.e Petroleum ether, benzene, chloroform, ethanol and methanol. Standard confirmation tests for all compounds were applied for analysis. Results revealed the presence of high range of bioactive compounds such as alakaloids, terpenoids, glycosides, steroids, flavonoids, saponins, phytosterols, oxalic acid, anthocyanin and quinone in both plants. Best results were obtained by methanolic, chloroform and petroleum ether extracts and methanolic, ethanolic and benzene extracts of Limium indicum and Euphorbia granulate respectively. Considering the results, methanolic extracts of both plants were further analysed for antibacterial activity. Plants were analysed against four pathogens including Escherchia coli, Proteus vulgaris, Klebsiella pneumonia and Pseudomonas aruginosa using disc diffusion method. Limium indicum showed highly significant activity against all pathogens while Euphorbia granulata showed significant activity against Klebsiella pneumonia and Proteus vulgaris but lesser against Escherchia coli and Pseudomonas aruginosa. MIC of extracts against each positive bacterium was calculated and recorded. Present plants can be considered for making useful drugs but further studies are needed to isolate active agents from plant extracts for drug development.

Keywords: antibacterial activity, Euphorbia granulata, Limium indicum, medicinal plants, phytochemical screening

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Authors: V. Swarnalatha, A. V. Narasimha Rao, P. Pal

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The present research reports the investigation of fast etching of silicon for the fabrication of microelectromechanical systems (MEMS) structures using silicon wet bulk micromachining. Low concentration tetramethyl-ammonium hydroxide (TMAH) and hydroxylamine (NH₂OH) are used as main etchant and additive, respectively. The concentration of NH₂OH is varied to optimize the composition to achieve best etching characteristics such as high etch rate, significantly high undercutting at convex corner for the fast release of the microstructures from the substrate, and improved etched surface morphology. These etching characteristics are studied on Si{100} and Si{110} wafers as they are most widely used in the fabrication of MEMS structures as wells diode, transistors and integrated circuits.

Keywords: KOH, MEMS, micromachining, silicon, TMAH, wet anisotropic etching

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Authors: Kushal Patel, Manasa Dittakavi, Cyrus Falsafi, Gretchen Lovett

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Rural America has seen a surge in opioid addiction rates and overdose deaths in recent years, becoming a significant public health crisis. This may be due to a variety of factors, such as lack of access to healthcare or other economic and social factors that can contribute to addiction such as poverty, unemployment, and social isolation. As the opioid epidemic has disproportionately affected rural communities, pregnant women in these areas may be highly susceptible and face additional difficulties in facing the appropriate care they need. Opioid use disorder has many negative effects on prenatal infants. These include changes in their microbiome, mental health, neurodevelopment and cognition. These can affect how the child performs in various activities in life and how they interact with others. It has been demonstrated that using cognitive behavioral therapy improves not just pain-related results but also mobility, quality of life, disability, and mood outcomes. This indicates that cognitive behavioral therapy (CBT) may be a useful therapeutic strategy for enhancing general health and wellbeing in people with opioid use problems. In terms of treating psychiatric diseases, CBT carries fewer dangers than opioids. One study that illustrates the potential for CBT to promote a reduction in opioid use disorder used self-reported drug use patterns 6 months prior to and during their pregnancy. At the beginning of the study, participants reported an average of 3.78 drug or alcohol use days in the previous 28 days, which decreased to 1.63 days after treatment. The study also found a decrease in depression scores, as measured by IDS scores, from 23.9 to 17.1 at the end of treatment. These and other results show that CBT can have meaningful impacts on pregnant women in Rural America who struggle with an opioid use disorder. This project has been approved by the West Virginia School of Osteopathic Medicine- Office of Research and Sponsored Programs and deemed non-research scholarly work.

Keywords: appalachia, CBT, opiods, pregnancy

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Authors: Yung-Chih Kuo, I-Hsin Wang

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Catanionic solid lipid nanoparticles (CASLNs) with surface wheat germ agglutinin (WGA) and lactoferrin (Lf) were formulated for entrapping and releasing etoposide (ETP), crossing the blood–brain barrier (BBB), and inhibiting the growth of glioblastoma multiforme (GBM). Microemulsified ETP-CASLNs were modified with WGA and Lf for permeating a cultured monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and for treating malignant U87MG cells. Experimental evidence revealed that an increase in the concentration of catanionic surfactant from 5 μM to 7.5 μM reduced the particle size. When the concentration of catanionic surfactant increased from 7.5 μM to 12.5 μM, the particle size increased, yielding a minimal diameter of WGA-Lf-ETP-CASLNs at 7.5 μM of catanionic surfactant. An increase in the weight percentage of BW from 25% to 75% enlarged WGA-Lf-ETP-CASLNs. In addition, an increase in the concentration of catanionic surfactant from 5 to 15 μM increased the absolute value of zeta potential of WGA-Lf-ETP-CASLNs. It was intriguing that the increment of the charge as a function of the concentration of catanionic surfactant was approximately linear. WGA-Lf-ETP-CASLNs revealed an integral structure with smooth particle contour, displayed a lighter exterior layer of catanionic surfactant, WGA, and Lf and showed a rigid interior region of solid lipids. A variation in the concentration of catanionic surfactant between 5 μM and 15 μM yielded a maximal encapsulation efficiency of ETP ata 7.5 μM of catanionic surfactant. An increase in the concentration of Lf/WGA decreased the grafting efficiency of Lf/WGA. Also, an increase in the weight percentage of ETP decreased its encapsulation efficiency. Moreover, the release rate of ETP from WGA-Lf-ETP-CASLNs reduced with increasing concentration of catanionic surfactant, and WGA-Lf-ETP-CASLNs at 12.5 μM of catanionic surfactant exhibited a feature of sustained release. The order in the viability of HBMECs was ETP-CASLNs ≅ Lf-ETP-CASLNs ≅ WGA-Lf-ETP-CASLNs > ETP. The variation in the transendothelial electrical resistance (TEER) and permeability of propidium iodide (PI) was negligible when the concentration of Lf increased. Furthermore, an increase in the concentration of WGA from 0.2 to 0.6 mg/mL insignificantly altered the TEER and permeability of PI. When the concentration of Lf increased from 2.5 to 7.5 μg/mL and the concentration of WGA increased from 2.5 to 5 μg/mL, the enhancement in the permeability of ETP was minor. However, 10 μg/mL of Lf promoted the permeability of ETP using Lf-ETP-CASLNs, and 5 and 10 μg/mL of WGA could considerably improve the permeability of ETP using WGA-Lf-ETP-CASLNs. The order in the efficacy of inhibiting U87MG cells was WGA-Lf-ETP-CASLNs > Lf-ETP-CASLNs > ETP-CASLNs > ETP. As a result, WGA-Lf-ETP-CASLNs reduced the TEER, enhanced the permeability of PI, induced a minor cytotoxicity to HBMECs, increased the permeability of ETP across the BBB, and improved the antiproliferative efficacy of U87MG cells. The grafting of WGA and Lf is crucial to control the medicinal property of ETP-CASLNs and WGA-Lf-ETP-CASLNs can be promising colloidal carriers in GBM management.

Keywords: catanionic solid lipid nanoparticle, etoposide, glioblastoma multiforme, lactoferrin, wheat germ agglutinin

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Authors: Mohammad Amjad Sabir, Ishtiaq Khan, Shahid Ali, Umar Shabbir, Aneel Ahmad

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Creep, being the main silt contributor to the rivers, is a slow, downhill flow of soils. The creep velocity is measured in millimeters to a couple of centimeters per year and is determined with the help of tilt caused by creep in the vertical objects and needs at least ten years to get a reliable creep velocity. This project was devised to calculate creep velocity using dendrochronology and looking for the difference of creep velocity registered by different trees on the same slope. It was concluded that dendrochronology provides a very reliable procedure of creep velocity estimation if ‘J’ shaped trees are studied for their horizontal movement and age. The age of these trees was measured using tree coring, and the horizontal movement was measured with a conventional tape. Using this procedure it does not require decades and additionally the data reveals the creep velocity for up to 150 years and even more instead of just a decade. It was also concluded that the creep velocity does not only depend on bulk density of soil hence no pronounced effect of bulk density was detected.

Keywords: creep velocity, Galiyat, Pakistan, dendrochronology, Nagri Bala

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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