Search results for: anti-cancer treatment

Authors: Suvorov Vasyl, Filipchuk Viktor

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Developmental Dysplasia of the Hip (DDH) is a frequent pathology in pediatric orthopedist’s practice. Neglected or residual cases of DDH in walking patients are usually treated using pelvic osteotomies. Plastic changes take place in hinge points due to acetabulum reorientation during surgery. Classically described hinge points and a traditional division of pelvic osteotomies on reshaping and reorientation are currently debated. The purpose of this article was to evaluate biomechanical changes during the most commonly used pelvic osteotomies (Salter, Dega, Pemberton) for DDH treatment in pediatric patients. Methods: virtual pelvic models of 2- and 6-years old patients were created, material properties were assigned, pelvic osteotomies were simulated and biomechanical changes were evaluated using finite element analysis (FEA). Results: it was revealed that the patient's age has an impact on pelvic bones and cartilages density (in younger patients the pelvic elements are more pliable - p<0.05). Stress distribution after each of the abovementioned pelvic osteotomy was assessed in 2- and 6-years old patients’ pelvic models; hinge points were evaluated. The new term "restriction point" was introduced, which means a place where restriction of acetabular deformity correction occurs. Pelvic ligaments attachment points were mainly these restriction points. Conclusions: it was found out that there are no purely reshaping and reorientation pelvic osteotomies as previously believed; the pelvic ring acts as a unit in carrying out the applied load. Biomechanical overload of triradiate cartilage during Salter osteotomy in 2-years old patient and in 2- and 6-years old patients during Pemberton osteotomy was revealed; overload of the posterior cortical layer in the greater sciatic notch in 2-years old patient during Dega osteotomy was revealed. Level of Evidence – Level IV, prognostic.

Keywords: developmental dysplasia of the hip, pelvic osteotomy, finite element analysis, hinge point, biomechanics

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Authors: Hatem H.Saleh

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The aim of the study was to examine the effect of different concentrations of crude actinidin enzyme extract from kiwifruit juice and distilled water on some quality attributes of Awassi rams meats. Twelve Awassi rams were divided into four groups, After exsanguinations of rams carcasses they were infused (10% body weight) with crude of actinidin enzyme extract of kiwifruit juice with 10 and 15% of extract, and other group was infused with distilled water and were compared with other groups a non infusion treatment which were acted as a control. Thereafter samples from two main muscles, namely longissimus dorsi (LD) and Semimembranosus (SM) of the carcasses was chilled then stored in freezing, until testing time . The results showed a decrease in the rate pH decline on LD and SM muscle which was measured at time (0, 3, 6, 9, 12, 24 hours) postmortem among different treatments, It also reported lower values of the rate pH on the LD and SM muscle during the first of 12 hrs postmortem. No significant differences of the rate internal meat temperature in LD and SM muscle were observed among treatments postmortem except decreased of internal meat temperature during 3 hours postmortem when treated with enzyme extract. The results recorded higher values of glycolysis rate (R-value) in LD and SM muscle when treated with enzyme extract. Treated LD and LM muscle samples with 10 and 15% of crude actinidin enzyme extract of kiwifruit juice led to improve water holding capacity and higher significant differences in total tyrosine/ tryptophan index (T.T/T) in LD and SM muscles comparison with treatment control. It could be concluded that extract of kiwifruit juice infusion is could be used to improve of meat tenderization.

Keywords: extract of kiwifruit, decline of pH and Temperature , R-value, tyrosine / tryptophan index, sheep meat

Procedia PDF Downloads 543

Authors: Hadjer Sadoune, Liza Lamini, Scherazade Krim, Amel Djouadi, Rachida Rihani

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Deep neural networks are highly regarded for their accuracy in predicting intricate fermentation processes. Their ability to learn from a large amount of datasets through artificial intelligence makes them particularly effective models. The primary obstacle in improving the performance of these models is to carefully choose the suitable hyperparameters, including the neural network architecture (number of hidden layers and hidden units), activation function, optimizer, learning rate, and other relevant factors. This study predicts biogas production from real wastewater treatment plant data using a sophisticated approach: hybrid Bayesian optimization with a tree-structured Parzen estimator (BO-TPE) for an optimised deep neural network (DNN) model. The plant utilizes an Upflow Anaerobic Sludge Blanket (UASB) digester that treats industrial wastewater from soft drinks and breweries. The digester has a working volume of 1574 m3 and a total volume of 1914 m3. Its internal diameter and height were 19 and 7.14 m, respectively. The data preprocessing was conducted with meticulous attention to preserving data quality while avoiding data reduction. Three normalization techniques were applied to the pre-processed data (MinMaxScaler, RobustScaler and StandardScaler) and compared with the Non-Normalized data. The RobustScaler approach has strong predictive ability for estimating the volume of biogas produced. The highest predicted biogas volume was 2236.105 Nm³/d, with coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) values of 0.712, 164.610, and 223.429, respectively.

Keywords: anaerobic digestion, biogas production, deep neural network, hybrid bo-tpe, hyperparameters tuning

Procedia PDF Downloads 38

Authors: Srisuporn Piyaratanawong, Suchai Assawapantanakul

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This study aims to reflect changes in beliefs and rituals among the Urak Lawoi sea gypsies on the Bulon archipelago of Satun Province that are related to changes of society according to each dimension of time. The historical study was conducted using an oral history approach. The study found that the traditional way of life as itinerants who moved seasonally resulted in their dependence on nature and beliefs in supernatural power, and mysterious powers and superstitions in the belief of ghosts, ancestors, guardian spirits, large banyan trees, life and living, treatment of diseases, king of nagas, and other beliefs. They displayed their respect to supernatural powers through rituals by worshiping, making offerings to spirits and performing Rongeng dance for spirits in return for fulfilling their vows. After World War II (1945), the Urak Lawoi sea gypsies on Bulon archipelago changed their itinerant way of life to permanent settlements. However, their beliefs in supernatural powers and ritual performances remained in existence. Until 1987, when tourism began to spread to the archipelago, some of them gradually turned to make a living with tourism. Moreover, during the last 20 years (from around 1994), Islam has spread among the people. With this social context, the traditional beliefs in supernatural powers have changed to beliefs according to the religion and the way of life that has changed. Thus, when the traditional beliefs and rituals can no longer fulfil the new way of life, they slowly disappear, such as the floating the boat ceremony that has been replaced with new beliefs and rituals according to Islam. Nevertheless, some beliefs and rituals still exist, such as beliefs about treatment of diseases and Rongeng dance for spirits in return for vow fulfilling. In conclusion, the traditional beliefs and rituals of the Urak Lawoi sea gypsies on the Bulon archipelago cannot fulfil the new way of life, and have, thus, brought about changes in beliefs and rituals that are congruent with the current society.

Keywords: belief, ritual, Urak Lawoi, sea gypsy, Bulon Archipelago

Procedia PDF Downloads 279

Authors: Mohanad Moustafa, Julia Sieberer, Rhys Davies

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Background: Orbital compartment syndrome (OCS) is a sight-threatening Ophthalmologic emergency caused by rapidly increasing intraorbital pressure. It is usually caused by a retrobulbar hemorrhage as a result of trauma. If not treated in a timely manner, permanent vision loss can occur. Lateral canthotomy and cantholysis are minor procedures that can be performed bedside with equipment available in the emergency department. The aim of the procedure is to release the attachments between the suspensory ligaments of the eye and the bony orbital wall, leading to a decrease in intraorbital pressure and preventing irreversible loss of vision. As most Ophthalmologists across the UK provide non-resident on-call service, this may lead to a delay in the treatment of OCS and stresses the need for Emergency medical staff to be able to provide this sight-saving procedure independently. Aim: To survey current training, experience, and confidence levels among Emergency Medicine doctors in performing emergency lateral canthotomy and to establish whether these variables change the following teaching from experienced ophthalmologists. RESULTS: Most EM registrars had little to no experience in performing lateral canthotomy and cantholysis. The majority of them showed a significant increase in their confidence to perform the procedure following ophthalmic-led teaching. The survey also showed that the registrars felt such training should be added to/part of the EM curriculum. Conclusion: The involvement of Ophthalmologists in the teaching of EM doctors to recognise and treat OCS independently may prevent delays in treatment and reduce the risk of permanent sight loss. This project showed potential in improving patient care and will lead to a National Survey of EM doctors across the UK.

Keywords: lateral canthotomy, retrobulbar hemorrhage, Ophthalmology, orbital compartment syndrome, sight loss, blindness

Procedia PDF Downloads 98

Authors: Salman Ahmad, Muhammad Aown Sammar Raza, Muhammad Farrukh Saleem, Rashid Iqbal, Muhammad Saqlain Zaheer, Muhammad Usman Aslam, Imran Haider, Muhammad Adnan Nazar, Muhammad Ali

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Among the various abiotic stresses, drought stress is one of the most challenging for field crops. Wheat is one of the major staple food of the world, which is highly affected by water deficit stress in the current scenario of climate change. In order to ensure food security by depleting water resources, there is an urgent need to adopt technologies which result in sufficient crop yield with less water consumption. Mulching and partial rootzone drying (PRD) are two important management techniques used for water conservation and to mitigate the negative impacts of drought. The experiment was conducted to screen out the best-suited mulch for wheat under PRD system. Two water application techniques (I1= full irrigation I2= PRD irrigation) and four mulch treatments (M0= un-mulched, M1= black plastic mulch, M2= wheat straw mulch and M4= cotton sticks mulch) were conducted in completely randomized design with four replications. The treatment, black plastic mulch was performed the best than other mulch treatments. For irrigation levels, higher values of growth, physiological and water-related parameters were recorded in control treatment while, quality traits and enzymatic activities were higher under partial root zone drying. The current study concluded that adverse effects of drought on wheat can be significantly mitigated by using mulches but black plastic mulch was best suited for partial rootzone drying irrigation system in wheat.

Keywords: antioxidants, leaf water relations, Mulches, osmolytes, partial root zone drying, photosynthesis

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Authors: María Cárdenas Gaudry, Gonzalo Ramces Fano Miranda

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Sediment removal is very important in the purification of water, not only for reasons of visual perception but also because of its association with odor and taste problems. The Cuchoquesera reservoir, which is in the Andean region of Ayacucho (Peru) at an altitude of 3,740 meters above sea level, visually presents suspended particles and organic impurities indicating that it contains water of dubious quality to deduce that it is suitable for direct consumption of human beings. In order to quantitatively know the degree of impurities, water quality monitoring was carried out from February to August 2018, in which four sampling stations were established in the reservoir. The selected measured parameters were electrical conductivity, total dissolved solids, pH, color, turbidity, and sludge volume. The indicators of the studied parameters exceed the permissible limits except for electrical conductivity (190 μS/cm) and total dissolved solids (255 mg/L). In this investigation, the best combination and the optimal doses of reagents were determined that allowed the removal of sediments from the waters of the Cuchoquesera reservoir, through the physicochemical process of coagulation-flocculation. In order to improve this process during the rainy season, six combinations of reagents were evaluated, made up of three coagulants (ferric chloride, ferrous sulfate, and aluminum sulfate) and two natural flocculants: prickly pear powder (Opuntia ficus-indica) and tara gum (Caesalpinia spinoza). For each combination of reagents, jar tests were developed following the central composite experimental design (CCED), where the design factors were the doses of coagulant and flocculant and the initial turbidity. The results of the jar tests were adjusted to mathematical models, obtaining that to treat the water from the Cuchoquesera reservoir, with a turbidity of 150 UTN and a color of 137 U Pt-Co, 27.9 mg/L of the coagulant aluminum sulfate with 3 mg/L of the natural tara gum flocculant to produce a purified water quality of 1.7 UTN of turbidity and 3.2 U Pt-Co of apparent color. The estimated cost of the dose of coagulant and flocculant found was 0.22 USD/m³. This is how “grey-green” technologies can be used as a combination in nature-based solutions in water treatment, in this case, to achieve potability, making it more sustainable, especially economically, if green technology is available at the site of application of the nature-based hybrid solution. This research is a demonstration of the compatibility of natural coagulants/flocculants with other treatment technologies in the integrated/hybrid treatment process, such as the possibility of hybridizing natural coagulants with other types of coagulants.

Keywords: prickly pear powder, tara gum, nature-based solutions, aluminum sulfate, jar test, turbidity, coagulation, flocculation

Procedia PDF Downloads 108

Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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Authors: Yong Hwang, Kang Yeol Suh, Yundeok Jang, Tae Hoon Kim

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Introduction: Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. Acute kidney injury is a potential complication of severe rhabdomyolysis and the prognosis is substantially worse if renal failure develops. We try to identify the factors that were predictive of AKI in severe trauma patients with rhabdomyolysis. Methods: This retrospective study was conducted at the emergency department of a level Ⅰ trauma center. Patients enrolled that initial creatine phosphokinase (CPK) levels were higher than 1000 IU with acute multiple trauma, and more than 18 years older from Oct. 2012 to June 2016. We collected demographic data (age, gender, length of hospital day, and patients’ outcome), laboratory data (ABGA, lactate, hemoglobin. hematocrit, platelet, LDH, myoglobin, liver enzyme, and BUN/Cr), and clinical data (Injury Mechanism, RTS, ISS, AIS, and TRISS). The data were compared and analyzed between AKI and Non-AKI group. Statistical analyses were performed using IMB SPSS 20.0 statistics for Window. Results: Three hundred sixty-four patients were enrolled that AKI group were ninety-six and non-AKI group were two hundred sixty-eight. The base excess (HCO3), AST/ALT, LDH, and myoglobin in AKI group were significantly higher than non-AKI group from laboratory data (p ≤ 0.05). The injury severity score (ISS), revised Trauma Score (RTS), Abbreviated Injury Scale 3 and 4 (AIS 3 and 4) were showed significant results in clinical data. The patterns of CPK level were increased from first and second day, but slightly decreased from third day in both group. Seven patients had received hemodialysis treatment despite the bleeding risk and were survived in AKI group. Conclusion: We recommend that HCO3, CPK, LDH, and myoglobin should be checked and be concerned about ISS, RTS, AIS with injury mechanism at the early stage of treatment in the emergency department.

Keywords: acute kidney injury, emergencies, multiple trauma, rhabdomyolysis

Procedia PDF Downloads 339

Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Gopal Lamichhane, Biswash Sapkota, Grinsun Sharma, Mahendra Adhikari

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Urolithiasis is a condition in which insoluble or less soluble salts like oxalate, phosphate etc. precipitate in urinary tract and causes obstruction in ureter resulting renal colic or sometimes haematuria. It is the third most common disorder of urinary tract affecting nearly 2% of world’s population. Poor urinary drainage, microbial infection, oxalate and calcium containing diet, calciferol, hyperparathyroidism, cysteine in urine, gout, dysfunction of intestine, drought environment, lifestyle, exercise, stress etc. are risk factors for urolithiasis. Wide ranges of treatments are available in allopathic system of medicine but reoccurrence is unpreventable even with the surgical removal of stone or lithotripsy. So, people prefer alternative medicinal systems such as Unani, homeopathic, ayurvedic etc. systems of medicine due to their fewer side effects over allopathic counterpart. Different plants based ethnomedicines are being well established by their continuous effective use in human since long time in treatment of urinary problem. Many studies have scientifically proved those ethnomedicines for antiurolithiatic effect in animal and in vitro model. Plant-based remedies were found to be therapeutically effective for both prevention as well as cure of calcium oxalate urolithiasis. Plants were known to show these effects through a combination of many effects such as antioxidant, diuretic, hypocalciuric, urine alkalinizing effect in them. Berberine, triterpenoids, lupeol are the phytochemicals established for antiurolithiatic effect. Hence, plant-based medicine can be the effective herbal alternative as well as means of discovery of novel drug molecule for curing urolithiatic disorder and should be focused on further research to discover their value in coming future.

Keywords: urolithiasis, herbal medicine, ethnomedicine, kidney stone, calcium oxalate

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

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Introduction: Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular malformation. It most often appears at birth or during the first days of life. Its origin is still unknown. It associates a livedo with telangiectasias of diffuse or segmental topography. In rare cases, it can be associated with neurological disorders such as macrocephaly and, less frequently, with epilepsy. Methodology: We report a case of an infant with Macrocephaly- Cutis marmorata telangiectatica congenita syndrome associated with epilepsy. Results: This is the case of a one month and 15 days old female infant from a non-consanguineous marriage, admitted for a status epilepticus in the context of apyrexia. Infectious and metabolic causes had been eliminated. Physical examination had shown non-infiltrated and reticular livedoid erythematous patches affecting the left upper limb and atrophic on the back of the left hand. Cerebral magnetic resonance imaging (MRI) showed thin layers of bifrontal, temporal, and left parietal hygromas associated with the widening of the bifrontal subarachnoid spaces. The electroencephalogram showed a well-organized sleep tracing with a single right occipital paroxysmal abnormality. Antiepileptic treatment has been administered with good clinical evolution and regression of the skin lesion and a control electroencephalogram without abnormality. Conclusion: This observation illustrates an association of CMTC with both macrocephaly and epilepsy. This pathology, which is relatively benign and has a good prognosis, generally does not require treatment. However, a detailed examination must be carried out, and a follow-up plan must be put in place for each patient presenting with CMTC, given the risk of association with other abnormalities, which can be potentially serious.

Keywords: cutis marmorata telangiectatica congenita, macrocephaly, epilepsy, children

Procedia PDF Downloads 60

Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni

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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.

Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis

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Authors: Parvaneh Eskandari, Rachel O'Reilly

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In the last years, controlling the self-assembly behavior of stimuli-responsive nano-objects, including micelles, vesicles, worm-like, etc., at different conditions is considered a pertinent challenge in the polymer community. The aim of the project was to synthesize aggregation-induced emission (AIE)-active stimuli-responsive polymeric nano-objects to control the self-assemblies morphologies of the prepared nano-objects. Two types of nanoobjects, micelle and vesicles, including PDMAEMA-b-P(BzMA-TPEMA) [PDMAEMA: poly(N,Ndimethylaminoethyl methacrylate); P(BzMA-TPEMA): poly[benzyl methacrylate-co- tetraphenylethene methacrylate]] were synthesized by using reversible addition−fragmentation chain-transfer (RAFT)- mediated polymerization-induced self-assembly (PISA), which combines polymerization and self-assembly in a single step. Transmission electron microscope and dynamic light scattering (DLS) analysis were used to confirm the formed self-assemblies morphologies. The controlled self-assemblies were applied as nitrophenolic compounds (NPCs) adsorbents from wastewater, thanks to their CO2-responsive part, PDMAEMA. Moreover, the fluorescence-active part of the prepared nano-objects, P(BzMA-TPEMA), played a key role in the detection of the NPCs at the aqueous solution. The optical properties of the prepared nano-objects were studied by UV/Vis and fluorescence spectroscopies. For responsivity investigations, the hydrodynamic diameter and Zeta-potential (ζ-potential) of the sample's aqueous solution were measured by DLS. In the end, the prepared nano-objects were used for the detection and adsorption of different NPCs.

Keywords: aggregation-induced emission polymers, stimuli-responsive polymers, reversible addition−fragmentation chain-transfer polymerization, polymerization-induced self-assembly, wastewater treatment

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Authors: Jaroslav Knapek, Kamila Vavrova, Tomas Kralik, Tereza Humesova

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The treatment and disposal of sewage sludge is one of the most important and critical problems of waste water treatment plants. Currently, 180 thousand tonnes of sludge dry matter are produced in the Czech Republic, which corresponds to approximately 17.8 kg of stabilized sludge dry matter / year per inhabitant of the Czech Republic. Due to the fact that sewage sludge contains a large amount of substances that are not beneficial for human health, the conditions for sludge management will be significantly tightened in the Czech Republic since 2023. One of the tested methods of sludge liquidation is the production of alternative fuel from sludge from sewage treatment plants and paper production. The paper presents an analysis of economic efficiency of alternative fuel production from sludge and its use for fluidized bed boiler with nominal consumption of 5 t of fuel per hour. The evaluation methodology includes the entire logistics chain from sludge extraction, through mechanical moisture reduction to about 40%, transport to the pelletizing line, moisture drying for pelleting and pelleting itself. For economic analysis of sludge pellet production, a time horizon of 10 years corresponding to the expected lifetime of the critical components of the pelletizing line is chosen. The economic analysis of pelleting projects is based on a detailed analysis of reference pelleting technologies suitable for sludge pelleting. The analysis of the economic efficiency of pellet is based on the simulation of cash flows associated with the implementation of the project over the life of the project. For the entered value of return on the invested capital, the price of the resulting product (in EUR / GJ or in EUR / t) is searched to ensure that the net present value of the project is zero over the project lifetime. The investor then realizes the return on the investment in the amount of the discount used to calculate the net present value. The calculations take place in a real business environment (taxes, tax depreciation, inflation, etc.) and the inputs work with market prices. At the same time, the opportunity cost principle is respected; waste disposal for alternative fuels includes the saved costs of waste disposal. The methodology also respects the emission allowances saved due to the displacement of coal by alternative (bio) fuel. Preliminary results of testing of pellet production from sludge show that after suitable modifications of the pelletizer it is possible to produce sufficiently high quality pellets from sludge. A mixture of sludge and paper waste has proved to be a more suitable material for pelleting. At the same time, preliminary results of the analysis of the economic efficiency of this sludge disposal method show that, despite the relatively low calorific value of the fuel produced (about 10-11 MJ / kg), this sludge disposal method is economically competitive. This work has been supported by the Czech Technology Agency within the project TN01000048 Biorefining as circulation technology.

Keywords: Alternative fuel, Economic analysis, Pelleting, Sewage sludge

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Authors: Rizvi Hasan

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Male factor infertility due to abnormalities in prolactin levels is encountered in a significant proportion. This was a case-control study carried out to determine the effects of prolactin abnormalities in normal males with infertility, recruiting 297 male infertile patients with informed written consent. All underwent a Basic Seminal Fluid Analysis (BSA) and endocrine profiles of FSH, LH, testosterone and prolactin (PRL) hormones using the random access chemiluminescent immunoassay method (normal range 2.5-17ng/ml). Age, weight, and height matched voluntary controls were recruited for comparison. None of the cases had anatomical, medical or surgical disorders related to infertility. Among the controls; mean age 33.2yrs ± 5.2, BMI 21.04 ± 1.39kgm-2, BSA 34×106, a number of children fathered 2±1, PRL 6.78 ± 2.92ng/ml. Of the 297 patients, 28 were hyperprolactinaemic while one was hypoprolactinaemic. All the hyperprolactinaemic patients had oligoasthenospermia, abnormal morphology and decreased viability. The serum testosterone levels were markedly lowered in 26 (92.86%) of the hyperprolactinaemic subjects. In the other 2 hyperprolactinaemic subjects and the single hypoprolactinaemic subject, the serum testosterone levels were normal. FSH and LH were normal in all patients. The 29 male patients with abnormalities in their serum PRL profiles were followed up for 12 months. The 28 patients suffering from hyperprolactinaemia were treated with oral bromocriptine in a dose of 2.5 mg twice daily. The hypoprolactinaemic patient defaulted treatment. From the follow-up, it was evident that 19 (67.86%) of the treated patients responded after 3 months of therapy while 4 (14.29%) showed improvement after approximately 6 months of bromocriptine therapy. One patient responded after 1 year of therapy while 2 patients showed improvements although not up to normal levels within the same period. Response to treatment was assessed by improvement in their BSA parameters. Prolactin abnormalities affect the male reproductive system and semen parameters necessitating further studies to ascertain the exact role of prolactin on the male reproductive tract. A parallel study was carried out incorporating 200 male white rats that were grouped and subjected to variations in their serum PRL levels. At the end of 100 days of treatment, these rats were subjected to morphological studies of their male reproductive tracts.Varying morphological changes depending on the levels of PRL changes induced were evident. Notable changes were arrest of spermatogenesis at the spermatid stage, a reduced testicular cellularity, a reduction in microvilli of the pseudostratified epithelial lining of the epididymis, while measurement of the tubular diameter showed a 30% reduction compared to normal tissue. There were no changes in the vas deferens, seminal vesicles, and the prostate. It is evident that both hyperprolactinaemia and hypoprolactinaemia have a direct effect on the morphology and function of the male reproductive tract. The morphological studies carried out on the groups of rats who were subjected to variations in their PRL levels could be the basis for infertility in male human beings.

Keywords: male factor infertility, morphological studies, prolactin, seminal fluid analysis

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Authors: Alessandra Pardu, Elena Curti, Marco Caredda, Alessio Dedola, Margherita Addis, Massimo Pes, Antonio Pirisi, Tonina Roggio, Sergio Uzzau, Roberto Anedda

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Some of the artisanal cheeses products of European Countries certificated as PDO (Protected Designation of Origin) are made from raw milk. To recognise potential frauds (e.g. pasteurisation or thermisation of milk aimed at raw milk cheese production), the alkaline phosphatase (ALP) assay is currently applied only for pasteurisation, although it is known to have notable limitations for the validation of ALP enzymatic state in nonbovine milk. It is known that frauds considerably impact on customers and certificating institutions, sometimes resulting in a damage of the product image and potential economic losses for cheesemaking producers. Robust, validated, and univocal analytical methods are therefore needed to allow Food Control and Security Organisms, to recognise a potential fraud. In an attempt to develop a new reliable method to overcome this issue, Time-Domain Nuclear Magnetic Resonance (TD-NMR) spectroscopy has been applied in the described work. Daily fresh milk was analysed raw (680.00 µL in each 10-mm NMR glass tube) at least in triplicate. Thermally treated samples were also produced, by putting each NMR tube of fresh raw milk in water pre-heated at temperatures from 68°C up to 72°C and for up to 3 min, with continuous agitation, and quench-cooled to 25°C in a water and ice solution. Raw and thermally treated samples were analysed in terms of 1H T2 transverse relaxation times with a CPMG sequence (Recycle Delay: 6 s, interpulse spacing: 0.05 ms, 8000 data points) and quasi-continuous distributions of T2 relaxation times were obtained by CONTIN analysis. In line with previous data collected by high field NMR techniques, a decrease in the spin-spin relaxation constant T2 of the predominant 1H population was detected in heat-treated milk as compared to raw milk. The decrease of T2 parameter is consistent with changes in chemical exchange and diffusive phenomena, likely associated to changes in milk protein (i.e. whey proteins and casein) arrangement promoted by heat treatment. Furthermore, experimental data suggest that molecular alterations are strictly dependent on the specific heat treatment conditions (temperature/time). Such molecular variations in milk, which are likely transferred to cheese during cheesemaking, highlight the possibility to extend the TD-NMR technique directly on cheese to develop a method for assessing a fraud related to the use of a milk thermal treatment in PDO raw milk cheese. Results suggest that TDNMR assays might pave a new way to the detailed characterisation of heat treatments of milk.

Keywords: cheese fraud, milk, pasteurisation, TD-NMR

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Authors: Guclu Insel, Efe Gumuslu, Gulten Yuksek, Nilay Sayi Ucar, Emine Ubay Cokgor, Tugba Olmez Hanci, Didem Okutman Tas, Fatos Germirli Babuna, Derya Firat Ertem, Okmen Yildirim, Ozge Erturan, Betul Kirci

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In order to eliminate water scarcity problems, effective precautions must be taken. Growing competition for water is increasingly forcing facilities to tackle their own water scarcity problems. At this point, application of wastewater reclamation and reuse results in considerable economic advantageous. In this study, an enamel coating facility, which is one of the high water consumed facilities, is evaluated in terms of its wastewater reuse potential. Wastewater reclamation and reuse can be defined as one of the best available techniques for this sector. Hence, process and pollution profiles together with detailed characterization of segregated wastewater sources are appraised in a way to find out the recoverable effluent streams arising from enamel coating operations. Daily, 170 m³ of process water is required and 160 m³ of wastewater is generated. The segregated streams generated by two enamel coating processes are characterized in terms of conventional parameters. Relatively clean segregated wastewater streams (reusable wastewaters) are separately collected and experimental treatability studies are conducted on it. The results reflected that the reusable wastewater fraction has an approximate amount of 110 m³/day that accounts for 68% of the total wastewaters. The need for treatment applicable on reusable wastewaters is determined by considering water quality requirements of various operations and characterization of reusable wastewater streams. Ultra-filtration (UF), Nano-filtration (NF) and Reverse Osmosis (RO) membranes are subsequently applied on reusable effluent fraction. Adequate organic matter removal is not obtained with the mentioned treatment sequence.

Keywords: enamel coating, membrane, reuse, wastewater reclamation

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Authors: Naso Isaiah Thanavisuth

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Introduction: Medical cannabis can be used for treatment, including anorexia, pain, inflammation, multiple sclerosis, Parkinson's disease, epilepsy, cancer, and metabolic syndrome-related disorders. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 (C430T) (Arg144Cys) and CYP2C9*3 on exon 7 (A1075C) (Ile359Leu) to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are a pharmacogenetics marker for prediction of THC-induced AEs in Thai patients. Objective: We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. Method: We enrolled 39 Thai patients with medical cannabis treatment consisting of men and women who were classified by clinical data. The quality of DNA extraction was assessed by using NanoDrop ND-1000. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay (ABI, Foster City, CA, USA). Results: All Thai patients who received the medical cannabis consist of twenty four (61.54%) patients who were female and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty nine (7.69%) and one of thirty nine (2.56%) , respectively. Conclusion: This is the first study to confirm the genetic polymorphism of CYP2C9 and medical cannabis-induced AEs in the Thai population. Although, our results indicates that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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Authors: Marilena Fatigante

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Contemporary psychoanalysis is increasingly acknowledging the existential demands of clients in psychotherapy. A significant aspect of the personal crises that patients face today is often rooted in the difficulty to find meaning in their own existence, even after working through or resolving traumatic memories and experiences. Tracing back to the correspondence between Freud and Romain Rolland (1927), psychoanalysis could not ignore that investigation of the psyche also encompasses the encounter with deep, psycho-sensory experiences, which involve a sense of "being one with the external world as a whole", the well-known “oceanic feeling”, as Rolland posed it. Despite the recognition of Non-ordinary States of Consciousness (NSC) as catalysts for transformation in clinical practice, highlighted by neuroscience and results from psychedelic-assisted therapies, there is few research on how psychoanalytic knowledge can integrate with other treatment traditions. These traditions, commonly rooted in non -Western, unconventional, and non-formal psychological knowledge, emphasize the individual’s innate tendency toward existential integrity and transcendence of self-boundaries. Inspired by an autobiographical account, this paper examines narratives of 12 individuals, who engaged in psychoanalytic therapy and also underwent treatment involving a non-formal helping relationship with an expert guide in consciousness, which included experience of this nature. The guide relies on 35 yrs of experience in Psychological, multidisciplinary studies in Human Sciences and Art, and demonstrates knowledge of many wisdom traditions, ranging from Eastern to Western philosophy, including Psychoanalysis and its development in cultural perspective (e.g, Ethnopsychiatry). Analyses focused primarily on two dimensions that research has identified as central in assessing the degree of treatment “success” in the patients’ narrative accounts of their therapies: agency and coherence, defined respectively as the increase, expressed in language, of the client’s perceived ability to manage his/her own challenges and the capacity, inherent in “narrative” itself as a resource for meaning making (Bruner, 1990), to provide the subject with a sense of unity, endowing his /her life experience with temporal and logical sequentiality. The present study reports that, in all narratives from the participants, agency and coherence are described differently than in “common” psychotherapy narratives. Although the participants consistently identified themselves as responsible agentic subject, the sense of agency derived from the non-conventional guidance pathway is never reduced to a personal, individual accomplishment. Rather, the more a new, fuller sense of “Life” (more than “Self”) develops out of the guidance pathway they engage with the expert guide, the more they “surrender” their own sense of autonomy and self-containment. Something, which Safran (2016) identified as well talking about the sense of surrender and “grace” in psychoanalytic sessions. Secondly, narratives of individuals engaging with the expert guide describe coherence not as repairing or enforcing continuity but as enhancing their ability to navigate dramatic discontinuities, falls, abrupt leaps and passages marked by feelings of loss and bereavement. The paper ultimately explores whether valid criteria can be established to analyze experiences of non-conventional paths of self-evolution. These paths are not opposed or alternative to conventional ones, and should not be simplistically dismissed as exotic or magical.

Keywords: oceanic feeling, non conventional guidance, consciousness, narratives, treatment outcomes

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Authors: Nalini Kaul, Barrie Drewitt, Elsie Kohoot

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Hyperpigmentation is the third most common pigmentary disorder where dermatologic treatment is sought. It affects all ages resulting in skin darkening because of melanin accumulation. An uneven skin tone because of either exposure to the sun (solar lentigos/age spots/sun spots or skin disruption following acne, or rashes (post-inflammatory hyperpigmentation -PIH) or hormonal changes (melasma) can lead to significant psychosocial impairment. Dyschromia is a result of various alterations in biochemical processes regulating melanogenesis. Treatments include the daily use of sunscreen with lightening, brightening, and exfoliating products. Depigmentation is achieved by various depigmenting agents: common examples are hydroquinone, arbutin, azelaic acid, aloesin, mulberry, licorice extracts, kojic acid, niacinamide, ellagic acid, arbutin, green tea, turmeric, soy, ascorbic acid, and tranexamic acid. These agents affect pigmentation by interfering with mechanisms before, during, and after melanin synthesis. While immediate correction is much sought after, patience and diligence are key. Our objective was to assess the effects of a facial product with pigmentation treatment and UV protection in 35 healthy F (35-65y), meeting the study criteria. Subjects with mild to moderate hyperpigmentation and fine lines with no use of skin-lightening products in the last six months or any dermatological procedures in the last twelve months before the study started were included. Efficacy parameters included expert clinical grading for hyperpigmentation, radiance, skin tone & smoothness, fine lines, and wrinkles bioinstrumentation (Corneometer®, Colorimeter®), digital photography and imaging (Visia-CR®), and self-assessment questionnaires. Safety included grading for erythema, edema, dryness & peeling and self-assessments for itching, stinging, tingling, and burning. Our results showed statistically significant improvement in clinical grading scores, bioinstrumentation, and digital photos for hyperpigmentation-brown spots, fine lines/wrinkles, skin tone, radiance, pores, skin smoothness, and overall appearance compared to baseline. The product was also well-tolerated and liked by subjects. Conclusion: Facial hyperpigmentation is of great concern, and treatment strategies are increasingly sought. Clinical trials with both subjective and objective assessments, imaging analyses, and self-perception are essential to distinguish evidence-based products. The multifunctional cosmetic product tested in this clinical study showed efficacy, tolerability, and subject satisfaction in reducing hyperpigmentation and global photoaging.

Keywords: hyperpigmentation; photoaging, clinical testing, expert visual evaluations, bio-instruments

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives: The duration of the disease could be one of the leading factors in the effectiveness of therapy in systemic sclerosis (SSc). The aim of the study was to assess how the duration of the disease affects the changes of lung function in patients(pts) with interstitial lung disease (ILD) associated with SSc during long-term RTX therapy. Methods: We prospectively included 113pts with SSc in this study. 85% of pts were female. Mean age was 48.1±13years. The diffuse cutaneous subset of the disease had 62pts, limited–40, overlap–11. The mean disease duration was 6.1±5.4years. Pts were divided into 2 groups depending on the disease duration - group 1 (less than 5 years-63pts) and group 2 (more than 5 years-50 pts). All pts received prednisolone at mean dose of 11.5±4.6 mg/day and 53 of them - immunosuppressants at inclusion. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3mo (point 1), 42±14mo (point 2) and 79±6.5mo (point 3) after initiation of RTX therapy. Cumulative mean dose of RTX in group 1 at point 1 was 1.7±0.6 g, at point 2 = 3.3±1.5g, at point 3 = 3.9±2.3g; in group 2 at point 1 = 1.6±0.6g, at point 2 = 2.7±1.5 g, at point 3 = 3.7±2.6 g. The results are presented in the form of mean values, delta(Δ), median(me), upper and lower quartile. Results. There was a significant increase of forced vital capacity % predicted (FVC) in both groups, but at points 1 and 2 the improvement was more significant in group 1. In group 2, an improvement of FVC was noted with a longer follow-up. Diffusion capacity for carbon monoxide % predicted (DLCO) remained stable at point 1, and then significantly improved by the 3rd year of RTX therapy in both groups. In group 1 at point 1: ΔFVC was 4.7 (me=4; [-1.8;12.3])%, ΔDLCO = -1.2 (me=-0.3; [-5.3;3.6])%, at point 2: ΔFVC = 9.4 (me=7.1; [1;16])%, ΔDLCO =3.7 (me=4.6; [-4.8;10])%, at point 3: ΔFVC = 13 (me=13.4; [2.3;25.8])%, ΔDLCO = 2.3 (me=1.6; [-5.6;11.5])%. In group 2 at point 1: ΔFVC = 3.4 (me=2.3; [-0.8;7.9])%, ΔDLCO = 1.5 (me=1.5; [-1.9;4.9])%; at point 2: ΔFVC = 7.6 (me=8.2; [0;12.6])%, ΔDLCO = 3.5 (me=0.7; [-1.6;10.7]) %; at point 3: ΔFVC = 13.2 (me=10.4; [2.8;15.4])%, ΔDLCO = 3.6 (me=1.7; [-2.4;9.2])%. Conclusion: Patients with an early SSc have more quick response to RTX therapy already in 1 year of follow-up. Patients with a disease duration more than 5 years also have response to therapy, but with longer treatment. RTX is effective option for the treatment of ILD-SSc, regardless of the duration of the disease.

Keywords: interstitial lung disease, systemic sclerosis, rituximab, disease duration

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Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

Abstract:

Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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Authors: Rachmat Mauludin, Novita R. Kusuma, Diky Mudhakir

Abstract:

Famotidine (FMT) is one of used substances in the treatment of hiperacidity and peptic ulcer, administered orally and parenterally via intravenous injection. Oral administration, which is more favorable, has been reported to have many obstacles in the process of the treatment, includes decreasing the bioavailability of FMT. This research was aimed to prepare FMT in form of solid lipid nanoparticles (SLN) with size ranging between 100-200 nm. The research was carried out also by optimizing factors that may affect physical stability of SLN. Formulation of Famotidine SLN was carried out by optimizing factors, such as duration of homogenization and sonication, lipid concentration, stabilizer composition and stabilizer concentration. SLN physical stability was evaluated (particle size distribution) for 42 days in 3 diferent temperatures. Entrapment efficiency and drug loading was determined indirectly and directly. The morphology of SLN was visualized by transmission electron microscope (TEM). In vitro release study of FMT was conducted in 2 mediums, at pH of 1.2 and 7.4. Chemical stability of FMT was determined by quantifying the concentration of FMT within 42 days. Famotidin SLN consisted of GMS as lipid and poloxamer 188, lecithin, and polysorbate 80 as stabilizers. Homogenization and sonication was performed for 5 minutes and 10 minutes. Physyical stability of nanoparticles at 3 different temperatures was no significant difference. The best formula was physically stable until 42 days with mean particle size below 200 nm. Nanoparticles produced was able to entrap FMT until 86.6%. Evaluation by TEM showed that nanoparticles was spherical and solid. In medium pH of 1.2, FMT was released only 30% during 4 hour. On the other hand, within 4 hours SLN could release FMT completely in medium pH of 7.4. The FMT concentration in nanoparticles dispersion was maintained until 95% in 42 days (40oC, RH 75%). Famotidine SLN was able to be produced with mean particle size ranging between 100-200 nm and physically stable for 42 days. SLN could be loaded by 86,6% of FMT. Morphologically, obtained SLN was spheric and solid. During 4 hours in medium pH of 1.2 and 7.4, FMT was released until 30% and 100%, respectively.

Keywords: solid lipid nanoparticle (SLN), famotidine (FMT), physicochemical properties, release study

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Authors: G. Traini, G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, S. M. Valle, C. Voena, V. Patera

Abstract:

In Particle Therapy (PT) treatments a large amount of secondary particles, whose emission point is correlated to the dose released in the crossed tissues, is produced. The measurement of the secondary charged fragments component could represent a valid technique to monitor the beam range during the PT treatments, that is a still missing item in the clinical practice. A sub-millimetrical precision on the beam range measurement is required to significantly optimise the technique and to improve the treatment quality. In this contribution, a detector, named Dose Profiler (DP), is presented. It is specifically planned to monitor on-line the beam range exploiting the secondary charged particles produced in PT Carbon ions treatment. In particular, the DP is designed to track the secondary fragments emitted at large angles with respect to the beam direction (mainly protons), with the aim to reconstruct the spatial coordinates of the fragment emission point extrapolating the measured track toward the beam axis. The DP is currently under development within of the INSIDE collaboration (Innovative Solutions for In-beam Dosimetry in hadrontherapy). The tracker is made by six layers (20 × 20 cm²) of BCF-12 square scintillating fibres (500 μm) coupled to Silicon Photo-Multipliers, followed by two plastic scintillator layers of 6 mm thickness. A system of front-end boards based on FPGAs arranged around the detector provides the data acquisition. The detector characterization with cosmic rays is currently undergoing, and a data taking campaign with protons will take place in May 2017. The DP design and the performances measured with using MIPs and protons beam will be reviewed.

Keywords: fragmentation, monitoring, particle therapy, tracking

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Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

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Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Tanyaporn Chairoch

Abstract:

Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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Authors: Lai Gwen Chan, Yining Ong, Audrey Yoke Poh Wong

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Background. The efficacy of electroconvulsive therapy (ECT) as a form of treatment to a range of mental disorders is well-established. However, ECT is often associated with either temporary or persistent cognitive side-effects, resulting in the failure of wider prescription. Of which, retrograde amnesia is the most commonly reported cognitive side-effect. Most studies found a recalling deficit in autobiographical memories to be short-term, although a few have reported more persistent amnesic effects. Little is known about ECT-related amnesic effects in Asian population. Hence, this study aims to resolve conflicting findings, as well as to better elucidate the effects of ECT on cognitive functioning in a local sample. Method: 12 patients underwent bilateral ECT under the care of Psychological Medicine Department, Tan Tock Seng Hospital, Singapore. Participants’ cognition and level of functioning were assessed at four time-points: before ECT, between the third and fourth induced seizure, at the end of the whole course of ECT, and two months after the index course of ECT. Results: It was found that Global Assessment of Functioning scores increased significantly at the completion of ECT. Case-by-case analyses also revealed an overall improvement in Personal Semantic and Autobiographical memory two months after the index course of ECT. A transient dip in both personal semantic and autobiographical memory scores was observed in one participant between the third and fourth induced seizure, but subsequently resolved and showed better performance than at baseline. Conclusions: The findings of this study suggest that ECT is an effective form of treatment to alleviate the severity of symptoms of the diagnosis. ECT does not affect attention, language, executive functioning, personal semantic and autobiographical memory adversely. The findings suggest that Asian patients may respond to bilateral ECT differently from Western samples.

Keywords: electroconvulsive therapy (ECT), autobiographical memory, cognitive impairment, psychiatric disorder

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Authors: Bernice Lottering, Yi-Wen Lin

Abstract:

Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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