Search results for: hyperthermic intra peritoneal chemotherapy

Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Ezzi Olfa, Bouafia Nabiha, Ammar Asma, Ben Cheikh Asma, Mahjoub Mohamed, Bannour Wadiaa, Achour Bechir, Khelif Abderrahim, Njah Mansour

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Background: In hematology/oncology, health care improvement has allowed increasingly aggressive management in diagnostic and therapeutic procedures. Nevertheless, these intensified procedures have been associated with higher risk of healthcare associated infections (HAIs). We undertook this study to estimate the burden of HAIs in the cancer patients in an onco -hematology unit in a Tunisian university hospital. Materials/Methods: A prospective, observational study, based on active surveillance for a period of 06 months from Mars through September 2016, was undertaken in the department of onco-hematology in a university hospital in Tunisia. Patients, who stayed in the unit for ≥ 48 h, were followed until hospital discharge. The Centers for Disease Control and Prevention criteria (CDC) for site-specific infections were used as standard definitions for HAIs. Results: One hundred fifty patients were included in the study. The gender distribution was 33.3% for girls and 66.6% boys. They have a mean age of 23.12 years (SD = 18.36 years). The main patient’s diagnosis is: Acute Lymphoblastic Leukemia (ALL): 48.7 %( n=73). The mean length of stay was 21 days +/- 18 days. Almost 8% of patients had an implantable port (n= 12), 34.9 % (n=52) had a lumber puncture and 42.7 % (n= 64) had a medullary puncture. Chemotherapy was instituted in 88% of patients (n=132). Eighty (53.3%) patients had neutropenia at admission. The incidence rate of HAIs was 32.66 % per patient; the incidence density was 15.73 per 1000 patient-days in the unit. Mortality rate was 9.3% (n= 14), and 50% of cases of death were caused by HAIs. The most frequent episodes of infection were: infection of skin and superficial mucosa (5.3%), pulmonary aspergillosis (4.6%), Healthcare associated pneumonia (HAP) (4%), Central venous catheter associated infection (4%), digestive infection (5%), and primary bloodstream infection (2.6%). Finally, fever of unknown origin (FUO) incidence rate was 14%. In case of skin and superficial infection (n= 8), 4 episodes were documented, and organisms implicated were Escherichia.coli, Geotricum capitatum and Proteus mirabilis. For pulmonary aspergillosis, 6 cases were diagnosed clinically and radiologically, and one was proved by positive aspergillus antigen in bronchial aspiration. Only one patient died due this infection. In HAP (6 cases), four episodes were diagnosed clinically and radiologically. No bacterial etiology was established in these cases. Two patients died due to HAP. For primary bloodstream infection (4 cases), implicated germs were Enterobacter cloacae, Geotricum capitatum, klebsiella pneumoniae, and Streptococcus pneumoniae. Conclusion: This type of prospective study is an indispensable tool for internal quality control. It is necessary to evaluate preventive measures and design control guides and strategies aimed to reduce the HAI’s rate and the morbidity and mortality associated with infection in a hematology/oncology unit.

Keywords: cohort prospective studies, healthcare associated infections, hematology oncology department, incidence

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Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Muhammad Abdul Basit Memon

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The importance of organizational knowledge sharing and knowledge management has been documented in numerous research studies in available literature, since knowledge sharing has been recognized as a founding pillar for superior organizational performance and a source of gaining competitive advantage. Built on this, most of the successful organizations perceive knowledge management and knowledge sharing as a concern of high strategic importance and spend huge amounts on the effective management and sharing of organizational knowledge. However, despite some very serious endeavors, many firms fail to capitalize on the benefits of knowledge sharing because of being unaware of the individual characteristics, interpersonal, organizational and contextual factors that influence knowledge sharing; simply the antecedent to knowledge sharing. The extant literature on antecedents to knowledge sharing, offers a range of antecedents mentioned in a number of research articles and research studies. Some of the previous studies about antecedents to knowledge sharing, studied antecedents to knowledge sharing regarding inter-organizational knowledge transfer; others focused on inter and intra organizational knowledge sharing and still others investigated organizational factors. Some of the organizational antecedents to KS can relate to the characteristics and underlying aspects of knowledge being shared e.g., specificity and complexity of the underlying knowledge to be transferred; others relate to specific organizational characteristics e.g., age and size of the organization, decentralization and absorptive capacity of the firm and still others relate to the social relations and networks of organizations such as social ties, trusting relationships, and value systems. In the same way some researchers have highlighted on only one aspect like organizational commitment, transformational leadership, knowledge-centred culture, learning and performance orientation and social network-based relationships in the organizations. A bulk of the existing research articles on antecedents to knowledge sharing has mainly discussed organizational or environmental factors affecting knowledge sharing. However, the focus, later on, shifted towards the analysis of individuals or personal determinants as antecedents for the individual’s engagement in knowledge sharing activities, like personality traits, attitude and self efficacy etc. For example, employees’ goal orientations (i.e. learning orientation or performance orientation is an important individual antecedent of knowledge sharing behaviour. While being consistent with the existing literature therefore, the antecedents to knowledge sharing can be classified as being individual and organizational. This paper is an endeavor to discuss a conceptual framework of the individual and organizational antecedents to knowledge sharing in the light of the available literature and empirical evidence. This model not only can help in getting familiarity and comprehension on the subject matter by presenting a holistic view of the antecedents to knowledge sharing as discussed in the literature, but can also help the business managers and especially human resource managers to find insights about the salient features of organizational knowledge sharing. Moreover, this paper can help provide a ground for research students and academicians to conduct both qualitative as well and quantitative research and design an instrument for conducting survey on the topic of individual and organizational antecedents to knowledge sharing.

Keywords: antecedents to knowledge sharing, knowledge management, individual and organizational, organizational knowledge sharing

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: Agnieszka P. Regiec

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Capital companies are based on monetary capital. In the traditional model, the capital is the sum of the nominal values of all shares issued. For a few years within the European countries, the limited liability companies’ (LLC) regulations are leaning towards liberalization of the capital structure in order to provide higher degree of autonomy regarding the intra-corporate governance. Reforms were based primarily on the legal system of the USA. In the USA, the tradition of no-par shares is well-established. Thus, as a point of reference, the American legal system is being chosen. Regulations of Germany, Great Britain, France, Netherlands, Finland, Poland and the USA will be taken into consideration. The analysis of the share capital is important for the development of science not only because the capital structure of the corporation has significant impact on the shareholders’ rights, but also it reflects on relationships between creditors of the company and the company itself. Multi-level comparative approach towards the problem will allow to present a wide range of the possible outcomes stemming from the novelization. The dogmatic method was applied. The analysis was based on the statutes, secondary sources and judicial awards. Both the substantive and the procedural aspects of the capital structure were considered. In Germany, as a result of the regulatory competition, typical for the EU, the structure of LLCs was reshaped. New LLC – Unternehmergesellschaft, which does not require a minimum share capital, was introduced. The minimum share capital for Gesellschaft mit beschrankter Haftung was lowered from 25 000 to 10 000 euro. In France the capital structure of corporations was also altered. In 2003, the minimum share capital of société à responsabilité limitée (S.A.R.L.) was repealed. In 2009, the minimum share capital of société par actions simplifiée – in the “simple” version of S.A.R.L. was also changed – there is no minimum share capital required by a statute. The company has to, however, indicate a share capital without the legislator imposing the minimum value of said capital. In Netherlands the reform of the Besloten Vennootschap met beperkte aansprakelijkheid (B.V.) was planned with the following change: repeal of the minimum share capital as the answer to the need for higher degree of autonomy for shareholders. It, however, preserved shares with nominal value. In Finland the novelization of yksityinen osakeyhtiö took place in 2006 and as a result the no-par shares were introduced. Despite the fact that the statute allows shares without face value, it still requires the minimum share capital in the amount of 2 500 euro. In Poland the proposal for the restructuration of the capital structure of the LLC has been introduced. The proposal provides among others: devaluation of the capital to 1 PLN or complete liquidation of the minimum share capital, allowing the no-par shares to be issued. In conclusion: American solutions, in particular, balance sheet test and solvency test provide better protection for creditors; European no-par shares are not the same as American and the existence of share capital in Poland is crucial.

Keywords: balance sheet test, limited liability company, nominal value of shares, no-par shares, share capital, solvency test

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Authors: Gergely Horvath

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The study analyzes the special provisions of the highest level of national agricultural legislation in the Fundamental Law of Hungary (25 April 2011) with descriptive, analytic and comparative methods. The agriculturally relevant articles of the constitution are very important, because –in spite of their high level of abstraction– they can determine and serve the practice comprehensively and effectively. That is why the objective of the research is to interpret the concrete sentences and phrases in connection with agriculture compared with the methods of some other relevant constitutions (historical-grammatical interpretation). The major findings of the study focus on searching for the appropriate provisions and approach capable of solving the problems of sustainable food production. The real challenge agricultural law must face with in the future is protecting or conserving its background and subjects: the environment, the ecosystem services and all the 'roots' of food production. In effect, agricultural law is the legal aspect of the production of 'our daily bread' from farm to table. However, it also must guarantee the safe daily food for our children and for all our descendants. In connection with sustainability, this unique, value-oriented constitution of an agrarian country even deals with uncustomary questions in this level of legislation like GMOs (by banning the production of genetically modified crops). The starting point is that the principle of public good (principium boni communis) must be the leading notion of the norm, which is an idea partly outside the law. The public interest is reflected by the agricultural law mainly in the concept of public health (in connection with food security) and the security of supply with healthy food. The construed Article P claims the general protection of our natural resources as a requirement. The enumeration of the specific natural resources 'which all form part of the common national heritage' also means the conservation of the grounds of sustainable agriculture. The reference of the arable land represents the subfield of law of the protection of land (and soil conservation), that of the water resources represents the subfield of water protection, the reference of forests and the biological diversity visualize the specialty of nature conservation, which is an essential support for agrobiodiversity. The mentioned protected objects constituting the nation's common heritage metonymically melt with their protective regimes, strengthening them and forming constitutional references of law. This regimes also mean the protection of the natural foundations of the life of the living and also the future generations, in the name of intra- and intergenerational equity.

Keywords: agricultural law, constitutional values, natural resources, sustainability

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Anna Ghosh, Dominic Shields, Ceri McIntosh, Stephen Crank

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A 29-year-old male was a referral to the maxillofacial unit following a referral from his general dental practitioner via a routine pathway regarding a large periapical lesion on the LR4 with root resorption. The patient was asymptomatic, the LR4 vital and unrestored, and this was an incidental finding at a routine check-up. The patient's past medical history was unremarkable. Examination revealed no extra or intra-oral pathology and non-mobile teeth. No focal neurology was detected. An orthopantogram demonstrated a well-defined unilocular corticated radiolucency associated with the LR4. The root appeared shortened with the radiolucency between the root and a radio-opacity, possibly representing the displacement of the apical tip of the tooth. It was recommended that the referring general practitioner should proceed with orthograde root canal therapy, after which time exploration, enucleation, and retrograde root filling of the LR4 would be carried out by a maxillofacial unit. The patient was reviewed six months later where, due to the COVID-19 pandemic, the patient had been unable to access general dental services for the root canal treatment. He was still entirely asymptomatic. A one-year review was planned in the hope this would allow time for the orthograde root canal therapy to be completed. At this review, the orthograde root canal therapy had still not been completed. Interestingly, a repeat orthopantogram revealed a significant reduction in size with good bony infill and a significant reduction in the size of the lesion. Due to the ongoing delays with primary care dental therapy, the patient was subsequently internally referred to the restorative dentistry department for care. The patient was seen again by oral and maxillo-facial surgery in mid-2022 where he still reports this tooth as asymptomatic with no focal neurology. The patient's history was fully reviewed, and noted that 15 years previously, the patient underwent open reduction and internal fixation of a left angle of mandible fracture. Temporary IMF involving IMF screws and fixation wires were employed to maintain occlusion during plating and subsequently removed post-operatively. It is proposed that the radiolucency was, as a result of the IMF screw placement, penetrating the LR4 root resulting in resorption of the tooth root and development of a radiolucency. This case highlights the importance of careful screw size and physical site location, and placement of IMF screws, as there can be permeant damage to a patient’s dentition.

Keywords: facial trauma, inter-maxillary fixation, mandibular radiolucency, oral and maxillo-facial surgery

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Authors: Virany Diana, Martono Tri Utomo, Risa Etika

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Background: Shock is one severe condition that can be a major cause of morbidity and mortality in the Neonatal Intensive Care Unit. Preterm infants are very susceptible to shock caused by many complications such as asphyxia, patent ductus arteriosus, intra ventricle haemorrhage, necrotizing enterocolitis, persistent pulmonal hypertension of the newborn, and septicaemia. Limited hemodynamic monitoring for early detection of shock causes delayed intervention and comprises the outcomes. Clinical parameters still used in neonatal shock detection, such as Capillary Refill Time, heart rate, cold extremity, and urine production. Blood pressure is most frequently used to evaluate preterm's circulation, but hypotension indicates uncompensated shock. Near-infrared spectroscopy (NIRS) is known as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Muscle oxygen saturation shows decreased cardiac output earlier than systemic parameters of tissue oxygenation when cerebral regional oxygen saturation is still stabilized by autoregulation. However, to our best knowledge, until now, no study has analyzed the decrease of muscle oxygen regional saturation (mRSO₂) and the ratio of muscle and cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Purpose: The purpose of this study is to analyze the decrease of mRSO₂ and ratio of muscle to cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Patients and Methods: This cross-sectional study was conducted on preterm infants with 28-34 weeks gestational age, admitted to the NICU of Dr. Soetomo Hospital from November to January 2022. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, prolonged CRT, cold extremity, decreased urine production, and MAP Blood Pressure less than GA in weeks). Measurement of mRSO₂ and cRSO₂ by NIRS was performed by the doctor in charge when the patient came to NICU. Results: We enrolled 40 preterm infants. The initial conventional hemodynamic parameter as the basic diagnosis of shock showed significant differences in all variables. Preterm with shock had higher mean HR (186.45±1.5), lower MAP (29.8±2.1), and lower SBP (45.1±4.28) than non-shock children, and most had a prolonged CRT. The patients’ outcome was not a significant difference between shock and non-shock patients. The mean mRSO₂ in the shock and non-shock groups were 33,65 ± 11,32 vs. 69,15 ± 3,96 (p=0.001), and the mean ratio mRSO₂/cRSO₂ 0,45 ± 0,12 vs. 0,84 ± 0,43 (p=0,001), were significantly different. The mean cRSO₂ in the shock and non-shock groups were 71,60 ± 4,90 vs. 81,85 ± 7,85 (p 0.082), not significantly different. Conclusion: The decrease of mRSO₂ and ratio of mRSO₂/cRSO₂ can differentiate between shock and non-shock in the preterm infant when cRSO₂ is still normal.

Keywords: preterm infant, regional muscle oxygen saturation, regional cerebral oxygen saturation, NIRS, shock

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Authors: F. A. Thomas, M. Schrafl-Altermatt, R. Treier, S. Kaufmann

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Stroke is the main cause of adult disability. Especially upper limb function is affected in most patients. Recently, cooperative hand movements have been shown to be a promising type of upper limb training in stroke rehabilitation. In these movements, which are frequently found in activities of daily living (e.g. opening a bottle, winding up a blind), the force of one upper limb has to be equally counteracted by the other limb to successfully accomplish a task. The use of standardized and reliable clinical assessments is essential to evaluate the efficacy of therapy and the functional outcome of a patient. Many assessments for upper limb function or impairment are available. However, the evaluation of cooperative hand movement tasks are rarely included in those. Thus, the aim of this study was (i) to develop a novel clinical assessment (CASA - Cooperative Activity Stroke Assessment) for the evaluation of patients’ capacity to perform cooperative hand movements and (ii) to test its inter- and interrater reliability. Furthermore, CASA scores were compared to current gold standard assessments for upper extremity in stroke patients (i.e. Fugl-Meyer Assessment, Box & Blocks Test). The CASA consists of five cooperative activities of daily living including (1) opening a jar, (2) opening a bottle, (3) open and closing of a zip, (4) unscrew a nut and (5) opening a clipbox. Here, the goal is to accomplish the tasks as fast as possible. In addition to the quantitative rating (i.e. time) which is converted to a 7-point scale, also the quality of the movement is rated in a 4-point scale. To test the reliability of CASA, fifteen stroke subjects were tested within a week twice by the same two raters. Intra-and interrater reliability was calculated using the intraclass correlation coefficient (ICC) for total CASA score and single items. Furthermore, Pearson-correlation was used to compare the CASA scores to the scores of Fugl-Meyer upper limb assessment and the box and blocks test, which were assessed in every patient additionally to the CASA. ICC scores of the total CASA score indicated an excellent- and single items established a good to excellent inter- and interrater reliability. Furthermore, the CASA score was significantly correlated to the Fugl-Meyer and Box & Blocks score. The CASA provides a reliable assessment for cooperative hand movements which are crucial for many activities of daily living. Due to its non-costly setup, easy and fast implementation, we suggest it to be well suitable for clinical application. In conclusion, the CASA is a useful tool in assessing the functional status and therapy related recovery in cooperative hand movement capacity in stroke patients.

Keywords: activitites of daily living, clinical assessment, cooperative hand movements, reliability, stroke

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Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

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Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

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Authors: Lexi Li

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This study aims to contribute to the field of how computer technology can be exploited to enhance EFL textbook design. Specifically, the study demonstrates how computerized native and learner corpora can be used to enhance modal verb treatment in EFL textbooks. The linguistic focus is will, would, can, could, may, might, shall, should, must. The native corpus is the spoken component of BNC2014 (hereafter BNCS2014). The spoken part is chosen because the pedagogical purpose of the textbooks is communication-oriented. Using the standard query option of CQPweb, 5% of each of the nine modals was sampled from BNCS2014. The learner corpus is the POS-tagged Ten-thousand English Compositions of Chinese Learners (TECCL). All the essays under the “secondary school” section were selected. A series of five secondary coursebooks comprise the textbook corpus. All the data in both the learner and the textbook corpora are retrieved through the concordance functions of WordSmith Tools (version, 5.0). Data analysis was divided into two parts. The first part compared the patterns of modal verbs in the textbook corpus and BNC2014 with respect to distributional features, semantic functions, and co-occurring constructions to examine whether the textbooks reflect the authentic use of English. Secondly, the learner corpus was compared with the textbook corpus in terms of the use (distributional features, semantic functions, and co-occurring constructions) in order to examine the degree of influence of the textbook on learners’ use of modal verbs. Moreover, the learner corpus was analyzed for the misuse (syntactic errors, e.g., she can sings*.) of the nine modal verbs to uncover potential difficulties that confront learners. The results indicate discrepancies between the textbook presentation of modal verbs and authentic modal use in natural discourse in terms of distributions of frequencies, semantic functions, and co-occurring structures. Furthermore, there are consistent patterns of use between the learner corpus and the textbook corpus with respect to the three above-mentioned aspects, except could, will and must, partially confirming the correlation between the frequency effects and L2 grammar acquisition. Further analysis reveals that the exceptions are caused by both positive and negative L1 transfer, indicating that the frequency effects can be intercepted by L1 interference. Besides, error analysis revealed that could, would, should and must are the most difficult for Chinese learners due to both inter-linguistic and intra-linguistic interference. The discrepancies between the textbook corpus and the native corpus point to a need to adjust the presentation of modal verbs in the textbooks in terms of frequencies, different meanings, and verb-phrase structures. Along with the adjustment of modal verb treatment based on authentic use, it is important for textbook writers to take into consideration the L1 interference as well as learners’ difficulties in their use of modal verbs. The present study is a methodological showcase of the combination both native and learner corpora in the enhancement of EFL textbook language authenticity and appropriateness for learners.

Keywords: EFL textbooks, learner corpus, modal verbs, native corpus

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Authors: Bar Y. Ainuz, Harry M. Salinas, Aleeza Ali, Eli B. Levitt, Austin J. Pourmoussa, Antoun Bouz, Miguel A. Medina

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Introduction: Breast conservation therapy remains the mainstay surgical treatment for early breast cancer. Oncoplastic techniques, in conjunction with lumpectomy and adjuvant radiotherapy, have been demonstrated to achieve good aesthetic results without adversely affecting cancer outcomes in the treatment of patients with macromastia or significant ptosis. In our patient population, many women present for breast conservation with pre-existing cosmetic implants or with breast volumes too small for soft tissue, only oncoplastic techniques. Our study evaluated a consecutive series of patients presenting for breast conservation undergoing concomitant oncoplastic-augmentation-mastopexy (OAM) with a contralateral augmentation-mastopexy for symmetry. Methods: OAM surgical technique involves simultaneous lumpectomy with exchange or placement of implants, oncoplastic mastopexy, and concomitant contralateral augmentation mastopexy for symmetry. Patients undergoing lumpectomy for breast conservation as outpatients were identified via retrospective chart review at a high volume private academic affiliated community-based cancer center. Patients with ptosis and either pre-existing breast implants or insufficient breast volume undergoing oncoplastic implant placement (or exchange) and mastopexy were included in the study. Operative details, aesthetic outcomes, and complications were assessed. Results: Over a continuous three-year period, with a two-surgeon cohort, 30 consecutive patients (56 breasts, 4 unilateral procedures) were identified. Patients had an average age of 52.5 years and an average BMI of 27.5, with 40% smokers or former smokers. The average operative time was 2.5 hours, the average implant size removed was 352 cc, and the average implant size placed was 300 cc. All new implants were smooth silicone, with the majority (92%) placed in a retropectoral fashion. 40% of patients received chemotherapy, and 80% of patients received whole breast adjuvant photon radiotherapy with a total radiation dose of either 42.56 or 52.56 Gy. The average and median length of follow-up were both 8.2 months. Of the 24 patients that received radiotherapy, 21% had asymmetry due to capsular contracture. A total of 7 patients (29.2%) underwent revisions for either positive margins (12.5%), capsular contracture (8.3%), implant loss (4.2%), or cosmetic concerns (4.2%). One patient developed a pulmonary embolism in the acute postoperative period and was treated with anticoagulant therapy. Conclusion: Oncoplastic augmentation mastopexy is a safe technique with good aesthetic outcomes and acceptable complication rates for ptotic patients with breast cancer and a paucity of breast volume or pre-existing implants who wish to pursue breast-conserving therapy. The revision rates compare favorably with single-stage cosmetic augmentation procedures as well as other oncoplastic techniques described in the literature. The short-term capsular contracture rates seem lower than the rates in patients undergoing radiation after mastectomy and implant-based reconstruction. Long term capsular contractures and revision rates are too early to know in this cohort.

Keywords: breast conserving therapy, oncoplastic augmentation mastopexy, capsular contracture, breast reconstruction

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Authors: Festa Shabani

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This paper aims at investigating bilingual speech in the International Schools of Prishtina. More particularly, it seeks to analyze bilingual phenomena among adolescent students highly exposed to English with the latter as the language of instruction at school in naturally-occurring conversations within school environment. Adolescence was deliberately chosen since it is regarded as an age when peer influence on language choice is the greatest. Driven by daily unsystematic observation and prior research already undertaken, the hypothesis stated is that Albanian continues to be the dominant language among Prishtina international schools’ students with a lot of code-switched items from the English. Furthermore, they will also use lexical borrowings - words already adapted in the receiving language, from the language they have been in contact with, in their speech often in the lack of existing equivalents in Albanian or for other reasons. This is done owing to the fact that the language of instruction at school is English, and any topic related to the language they have been exposed to will trigger them to use English. Therefore, this needs special attention in an attempt to identify patterns of their speech; in this way, linguistic and socio-pragmatic factors will be considered when analyzing the motivations behind their language choice. Methodology for collecting data include participant systematic observation and tape-recording. While observing them in their natural conversations, the fieldworker also took notes, which helped transcribe details better. The paper starts by raising the question of whether code-switching is occurring among Prishtina International Schools’ students highly exposed to English. The data gathered from students in informal settings suggests that there are well-founded grounds for an affirmative answer. The participants in this study are observed to be code-switching, although showing differences in degree. However, a generalization cannot be made on the basis of the findings except in so far it appears that English has, in turn, became a language to which they turn when identifying with the group when discussing about particular school topics. Particularly, participants seemed to use intra-sentential CS in cases when they seem to find an English expression rather easier than an Albanian one when repeating or emphasizing a point when urged to talk about educational issues with English being their language of instruction, and inter-sentential code-switching, particularly when quoting others. Concerning the grammatical aspect of code-switching, the intrasentential CS is used more than the intersentetial one. Speaking of gender, the results show that there were really no significant differences in regards quantity between male and female participants. However, the slight tendency for men to code switch intrasententially more than women was manifested. Similarly, a slight tendency again for a difference to emerge is on intersentential switching, which contributes 21% to the total number of switches for women, but 11% to the total number of switches for men.

Keywords: Albanian, code-switching contact linguistics, bilingual phenomena, lexical borrowing, English

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Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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Authors: Bharti Singh, Shri K. Singh

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Child malnutrition is a multifaceted issue that transcends geographical boundaries. Malnutrition not only stunts physical growth but also leads to a spectrum of morbidities and child mortality. It is one of the leading causes of death (~50 %) among children under age five. Despite economic progress and advancements in healthcare, child malnutrition remains a formidable challenge for India. The objective is to investigate the impact of women's empowerment on child nutrition outcomes in India from 2006 to 2021. A composite index of women's empowerment was constructed using Confirmatory Factor Analysis (CFA), a rigorous technique that validates the measurement model by assessing how well-observed variables represent latent constructs. This approach ensures the reliability and validity of the empowerment index. Secondly, kernel density plots were utilised to visualise the distribution of key nutritional indicators, such as stunting, wasting, and overweight. These plots offer insights into the shape and spread of data distributions, aiding in understanding the prevalence and severity of malnutrition. Thirdly, linear polynomial graphs were employed to analyse how nutritional parameters evolved with the child's age. This technique enables the visualisation of trends and patterns over time, allowing for a deeper understanding of nutritional dynamics during different stages of childhood. Lastly, multilevel analysis was conducted to identify vulnerable levels, including State-level, PSU-level, and household-level factors impacting undernutrition. This approach accounts for hierarchical data structures and allows for the examination of factors at multiple levels, providing a comprehensive understanding of the determinants of child malnutrition. Overall, the utilisation of these statistical methodologies enhances the transparency and replicability of the study by providing clear and robust analytical frameworks for data analysis and interpretation. Our study reveals that NFHS-4 and NFHS-5 exhibit an equal density of severely stunted cases. NFHS-5 indicates a limited decline in wasting among children aged five, while the density of severely wasted children remains consistent across NFHS-3, 4, and 5. In 2019-21, women with higher empowerment had a lower risk of their children being undernourished (Regression coefficient= -0.10***; Confidence Interval [-0.18, -0.04]). Gender dynamics also play a significant role, with male children exhibiting a higher susceptibility to undernourishment. Multilevel analysis suggests household-level vulnerability (intra-class correlation=0.21), highlighting the need to address child undernutrition at the household level.

Keywords: child nutrition, India, NFHS, women’s empowerment

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Authors: Margarita S. Tikhonova, Alireza Baniasad, Anton G. Kalmykov, Georgy A. Kalmykov, Ralf Littke

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There is a high complexity in the pore structure of organic-rich rocks caused by the combination of inter-particle porosity from inorganic mineral matter and ultrafine intra-particle porosity from both organic matter and clay minerals. Fluids are retained in that pore space, but there are major uncertainties in how and where the fluids are stored and to what extent they are accessible or trapped in 'closed' pores. A large degree of tortuosity may lead to fractionation of organic matter so that the lighter and flexible compounds would diffuse to the reservoir whereas more complicated compounds may be locked in place. Additionally, parts of hydrocarbons could be bound to solid organic matter –kerogen– and mineral matrix during expulsion and migration. Larger compounds can occupy thin channels so that clogging or oil and gas entrapment will occur. Sequential extraction of applying different solvents is a powerful tool to provide more information about the characteristics of trapped organic matter distribution. The Upper Jurassic – Lower Cretaceous Bazhenov shale is one of the most petroliferous source rock extended in West Siberia, Russia. Concerning the variable mineral composition, pore space distribution and thermal maturation, there are high uncertainties in distribution and composition of organic matter in this formation. In order to address this issue geological and geochemical properties of 30 samples including mineral composition (XRD and XRF), structure and texture (thin-section microscopy), organic matter contents, type and thermal maturity (Rock-Eval) as well as molecular composition (GC-FID and GC-MS) of different extracted materials during sequential extraction were considered. Sequential extraction was performed by a Soxhlet apparatus using different solvents, i.e., n-hexane, chloroform and ethanol-benzene (1:1 v:v) first on core plugs and later on pulverized materials. The results indicate that the studied samples are mainly composed of type II kerogen with TOC contents varied from 5 to 25%. The thermal maturity ranged from immature to late oil window. Whereas clay contents decreased with increasing maturity, the amount of silica increased in the studied samples. According to molecular geochemistry, stored hydrocarbons in open and closed pore space reveal different geochemical fingerprints. The results improve our understanding of hydrocarbon expulsion and migration in the organic-rich Bazhenov shale and therefore better estimation of hydrocarbon potential for this formation.

Keywords: Bazhenov formation, bitumen, molecular geochemistry, sequential extraction

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: N. Rambabu, H. Gururaj, Reynold Washington, Oommen George

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Motivation: Under the USAID Strengthening Health Outcomes through Private Sector (SHOPS-TB) initiative, Karnataka Health Promotion Trust (KHPT) with technical support of Abt associates is implementing a TB prevention and care model in Karnataka State, South India. KHPT is the interface agency between the public and private sectors, and providers and the target community facilitating early TB case detection and enhancing treatment compliance through private health care providers (pHCP) engagement in RNTCP. The project coverage is 0.84 million urban poor from 663 slums in 12 districts of Karnataka. Problem Statement: India with the highest burden of global TB (26%) and two million cases annually, accounts for approximately one fifth of the global incidence. WHO estimates 300,000 people die from TB annually in India. India expanded the coverage of Directly Observed Treatment, Short-course chemotherapy (DOTS) to the entire country as early as 2006. However, the performance of RNTCP has not been uniform across states. While the national annual new smear-positive (NSP) case notification rate is 53, it is much lower at 47 in Karnataka. A third of TB patients in India reside in urban slums. Approach: Under SHOPS, KHPT actively engages with communities through key opinion leaders and community structures. Interpersonal communication, by Outreach workers through house-to-house visits and at aggregation points, is the primary method used for communication about TB and its management and to increase demand for sputum examination and DOTS. pHCP are mapped, trained and mentored by KHPT. ORWs also provide patient and family counseling on TB treatment, side effects and adherence, screen close contacts of index patients especially children under 6 years of age and screen co-morbidities including HIV, diabetes and malnutrition and risk factors including alcoholism, tobacco use, occupational hazards making appropriate accompanied or documented referrals. A treatment ‘buddy’ system for the patients involving close friends or family members, ICT-based support, DOTS Prerana (inspiration) groups of TB patients, family members and community, DOTS Mitra (friend) helpline services are also used for care and support services. Results: The intervention educated 39988 slum dwellers, referred 1731 chest symptomatics, tested 1061 patients and initiated 248 patients on anti-TB treatment within three months of intervention through continuous community engagement. Conclusions: The intervention’s potential to increase access to preferred health care providers, reduce patient and health system delays in diagnosis and initiation of treatment, improve health seeking behaviour and enhance compliance of pHCPs to standard treatment protocols is being monitored. Initial results are promising.

Keywords: DOTS, KHPT, health outcomes, public and private sector

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Authors: Maria Amaia Iza Padilla, Ibai Ostolozaga

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The objective of this paper is to analyze how transportation costs between regions within a country can affect not only domestic trade but also the allocation of resources in a given region, aggregate productivity, and relative domestic prices (tradable versus non-tradable). On the one hand, there is a vast literature that analyzes the transportation costs faced by countries when trading with the rest of the world. However, this paper focuses on the effect of transportation costs on domestic trade. Countries differ in their domestic road infrastructure and transport quality. There is also some literature that focuses on the effect of road infrastructure on the price difference between regions but not on relative prices at the aggregate level. On the other hand, this work is also related to the literature on resource misallocation. Finally, the paper is also related to the literature analyzing the effect of trade on the development of the manufacturing sector. Using the World Bank Enterprise Survey database, it is observed cross-country differences in the proportion of firms that consider transportation as an obstacle. From the International Comparison Program, we obtain a significant negative correlation between GDP per worker and relative prices (manufacturing sector prices relative to the service sector). Furthermore, there is a significant negative correlation between a country’s transportation quality and the relative price of manufactured goods with respect to the price of services in that country. This is consistent with the empirical evidence of a negative correlation between transportation quality and GDP per worker, on the one hand, and the negative correlation between GDP per worker and domestic relative prices, on the other. It is also shown that in a country, the share of manufacturing firms whose main market is at the local (regional) level is negatively related to the quality of the transportation infrastructure within the country. Similarly, this index is positively related to the share of manufacturing firms whose main market is national or international. The data also shows that those countries with a higher proportion of manufacturing firms operating locally have higher relative prices. With this information in hand, the paper attempts to quantify the effects of the allocation of resources between and within sectors. The higher the trade barriers caused by transportation costs, the less efficient allocation, which causes lower aggregate productivity. Second, it is built a two-sector model where regions within a country trade with each other. On the one hand, it is found that with respect to the manufacturing sector, those countries with less trade between their regions will be characterized by a smaller variety of goods, less productive manufacturing firms on average, and higher relative prices for manufactured goods relative to service sector prices. Thus, the decline in the relative price of manufactured goods in more advanced countries could also be explained by the degree of trade between regions. This trade allows for efficient intra-industry allocation (traders are more productive, and resources are allocated more efficiently)).

Keywords: misallocation, relative prices, TFP, transportation cost

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Authors: William Creighton, Jan Smitheram

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Queer discourse has been tied to a middle-class, urban-centric, white approach to the discussion of queerness. In doing so, the multilayeredness of queer existence has been washed away in favour of palatable queer occupation. This paper uses design to explore a queer anti-urbanist approach to facilitate a more egalitarian architectural occupancy. Scott Herring’s work on queer anti-urbanism is key to this approach. Herring redeploys anti-urbanism from its historical understanding of open hostility, rejection and desire to destroy the city towards a mode of queer critique that counters normative ideals of homonormative metronormative gay lifestyles. He questions how queer identity has been closed down into a more diminutive frame where those who do not fit within this frame are subjected to persecution or silenced through their absence. We extend these ideas through design to ask how a queer anti-urbanist approach facilitates a more egalitarian architectural occupancy. Following a “design as research” methodology, the design outputs allow a vehicle to ask how we might live, otherwise, in architectural space. A design as research methodologically is a process of questioning, designing and reflecting – in a non-linear, iterative approach – establishes itself through three projects, each increasing in scale and complexity. Each of the three scales tackled a different body relationship. The project began exploring the relations between body to body, body to known others, and body to unknown others. Moving through increasing scales was not to privilege the objective, the public and the large scale; instead, ‘intra-scaling’ acts as a tool to re-think how scale reproduces normative ideas of the identity of space. There was a queering of scale. Through this approach, the results were an installation that brings two people together to co-author space where the installation distorts the sensory experience and forces a more intimate and interconnected experience challenging our socialized proxemics: knees might touch. To queer the home, the installation was used as a drawing device, a tool to study and challenge spatial perception, drawing convention, and as a way to process practical information about the site and existing house – the device became a tool to embrace the spontaneous. The final design proposal operates as a multi-scalar boundary-crossing through “private” and “public” to support kinship through communal labour, queer relationality and mooring. The resulting design works to set adrift bodies in a sea of sensations through a mix of pleasure programmes. To conclude, through three design proposals, this design research creates a relationship between queer anti-urbanism and design. It asserts that queering the design process and outcome allows a more inclusive way to consider place, space and belonging. The projects lend to a queer relationality and interdependence by making spaces that support the unsettled, out-of-place, but is it queer enough?

Keywords: queer, queer anti-urbanism, design as research, design

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Authors: Visith Siriphuwanun, Yodying Punjasawadwong, Suwinai Saengyo, Kittipan Rerkasem

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Objective: To determine incidences and factors associated with perioperative cardiac arrest in trauma patients who received anesthesia for emergency surgery. Design and setting: Retrospective cohort study in trauma patients during anesthesia for emergency surgery at a university hospital in northern Thailand country. Patients and methods: This study was permitted by the medical ethical committee, Faculty of Medicine at Maharaj Nakorn Chiang Mai Hospital, Thailand. We clarified data of 19,683 trauma patients receiving anesthesia within a decade between January 2007 to March 2016. The data analyzed patient characteristics, traumas surgery procedures, anesthesia information such as ASA physical status classification, anesthesia techniques, anesthetic drugs, location of anesthesia performed, and cardiac arrest outcomes. This study excluded the data of trauma patients who had received local anesthesia by surgeons or monitoring anesthesia care (MAC) and the patient which missing more information. The factor associated with perioperative cardiac arrest was identified with univariate analyses. Multiple regressions model for risk ratio (RR) and 95% confidence intervals (CI) were used to conduct factors correlated with perioperative cardiac arrest. The multicollinearity of all variables was examined by bivariate correlation matrix. A stepwise algorithm was chosen at a p-value less than 0.02 was selected to further multivariate analysis. A P-value of less than 0.05 was concluded as statistically significant. Measurements and results: The occurrence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was 170.04 per 10,000 cases. Factors associated with perioperative cardiac arrest in trauma patients were age being more than 65 years (RR=1.41, CI=1.02–1.96, p=0.039), ASA physical status 3 or higher (RR=4.19–21.58, p < 0.001), sites of surgery (intracranial, intrathoracic, upper intra-abdominal, and major vascular, each p < 0.001), cardiopulmonary comorbidities (RR=1.55, CI=1.10–2.17, p < 0.012), hemodynamic instability with shock prior to receiving anesthesia (RR=1.60, CI=1.21–2.11, p < 0.001) , special techniques for surgery such as cardiopulmonary bypass (CPB) and hypotensive techniques (RR=5.55, CI=2.01–15.36, p=0.001; RR=6.24, CI=2.21–17.58, p=0.001, respectively), and patients who had a history of being alcoholic (RR=5.27, CI=4.09–6.79, p < 0.001). Conclusion: Incidence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was very high and correlated with many factors, especially age of patient and cardiopulmonary comorbidities, patient having a history of alcoholic addiction, increasing ASA physical status, preoperative shock, special techniques for surgery, and sites of surgery including brain, thorax, abdomen, and major vascular region. Anesthesiologists and multidisciplinary teams in pre- and perioperative periods should remain alert for warning signs of pre-cardiac arrest and be quick to manage the high-risk group of surgical trauma patients. Furthermore, a healthcare policy should be promoted for protecting against accidents in high-risk groups of the population as well.

Keywords: perioperative cardiac arrest, trauma patients, emergency surgery, anesthesia, factors risk, incidence

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Authors: Seydou Drabo

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This paper examines how traditional contraceptives and abortion practices challenges the use of modern contraceptives in Burkina Faso. It demonstrates how fears and ‘superstitions’ interact with knowledge about modern contraceptives methods to determine use in a context where other way of controlling fertility (traditional contraceptives, abortion) are available to women in the public, private and traditional health sectors. Furthermore, these issues come at the time when Burkina Faso is among countries with a high fertility rate which (6.0 in 2010) and a very low used of contraceptives as only 16% of married women of childbearing age were using a contraceptive method in 2010. The country also has a young population since 33 % of the population is between 10-24 years old and this number is expected to increase by 2050, generating fears that a growing population of youth will put excessive pressure on available resources, including access to education, health services, and employment. Despite over two decades of dedicated policy attention, 24% of women of reproductive age (15-49) was estimated to have an unmet need for contraception in 2010. This paper draws on ethnographic fieldwork conducted since march 2016 (The research is still in progress) in Burkina Faso. Data were collected from 25 women (users and non-users of modern contraceptives and /or traditional contraceptives, post abortion care patients), 4 street drugs vendors and 3 traditional healers through formal and informal interviews, as well as direct observation. The findings show that a variety of contraceptives methods and abortion drugs or methods, both traditional and modern circulate and are available to women. Traditional contraceptives called African contraceptives by some of our participants refer to several birth control method including plants decoction, magical ring, waist necklace, a ritual done with a mixture of lay coming from termite mound and menses. Abortion is a practice that is done in secret through the use of abortion drugs or through intra uterine manoeuvres. Modern contraceptives include Oral contraceptive, implants, injectable. Stereotypes about modern contraceptives, having regular menstrual cycles and adopt of natural birth control methods, bad experience with modern contraceptives methods, the side effect of modern contraceptives, irregularity of sexual activities and the availability of emergency contraceptives are among factors that limit their use among women. In addition, a negative perception is built around modern contraceptives seen as the drug of ‘white people’. In general, the information on these drugs circulates in women’s social network (first line of information on contraceptive). Some women prefer using what they call African contraceptives or inducing an abortion over modern contraceptives because of their side effect. Furthermore, the findings show that women practices and attitudes in controlling birth varies throughout different phases of their lives. Beyond global discourses and technical solution, the issue of Family planning is all about social practices.

Keywords: abortion, Burkina Faso, contraception, culture, women

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Authors: Rahimi-Movaghar Vafa, Mansouri Pejman, Chardoli Mojtaba, Rezvani Samina

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Introduction: Blunt abdominal trauma is one of the leading causes of morbidity and mortality in all age groups, but diagnosis of serious intra-abdominal pathology is difficult and most of the damages are obscure in the initial investigation. There is still controversy about which patients should undergo abdomen/pelvis CT, which patients needs more observation and which patients can be discharged safely The aim of this study was to determine that is it safe to discharge patients with blunt abdominal trauma with normal initial findings. Methods: This non-randomized cross-sectional study was conducted from September 2013 to September 2014 at two levels I trauma centers, Sina hospital and Rasoul-e-Akram hospital (Tehran, Iran). Our inclusion criteria were all patients were admitted for suspicious BAT and our exclusion criteria were patients that have serious head and neck, chest, spine and limb injuries which need surgical intervention, those who have unstable vital signs, pregnant women with a gestational age over 3 months and homeless or without exact home address. 390 patients with blunt trauma abdomen examined and the necessary data, including demographic data, the abdominal examination, FAST result, patients’ lab test results (hematocrit, base deficit, urine analysis) on admission and at 6 and 12 hours after admission were recorded. Patients with normal physical examination, laboratory tests and FAST were discharged from the ED during 12 hours with the explanation of the alarm signs and were followed up after 24 hours and 1 week by a telephone call. Patients with abnormal findings in physical examination, laboratory tests, and FAST underwent abdomino-pelvic CT scan. Results: The study included 390 patients with blunt abdominal trauma between 12 and 80 years of age (mean age, 37.0 ± 13.7 years) and the mean duration of hospitalization in patients was 7.4 ± 4.1 hours. 88.6% of the patients were discharged from hospital before 12 hours. Odds ratio (OR) for having any symptoms for discharge after 6 hours was 0.160 and after 12 hours was 0.117 hours, which is statistically significant. Among the variables age, systolic and diastolic blood pressure, heart rate, respiratory rate, hematocrit and base deficit at admission, 6 hours and 12 hours after admission showed no significant statistical relationship with discharge time. From our 390 patients, 190 patients have normal initial physical examination, lab data and FAST findings that didn’t show any signs or symptoms in their next assessment and in their follow up by the phone call. Conclusion: It is recommended that patients with no symptoms at admission (completely normal physical examination, ultrasound, normal hematocrit and normal base deficit and lack of microscopic hematuria) and good family and social status can be safely discharged from the emergency department.

Keywords: blunt abdominal trauma, patient discharge, emergency department, FAST

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Authors: Anuj Pathare, Aleksandra Birn-Jeffery

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Background: The Anterior Cruciate Ligament(ACL) helps stabilize the knee joint minimizing tibial anterior translation. Anterior Cruciate Ligament (ACL) injury is common in racquet sports and often occurs due to sudden acceleration, deceleration or changes of direction. This mechanism in badminton most commonly occurs during landing after an overhead stroke. Knee biomechanics during dynamic movements such as walking, running and stair negotiation, do not return to normal for more than a year after an ACL reconstruction. This change in the biomechanics may lead to re-injury whilst performing non-steady movements during sports, where these injuries are most prevalent. Aims: To compare if the knee kinetics and kinematics in ACL injury recovered athletes return to the same level as those from an uninjured cohort during standard movements used for clinical assessment and badminton shots. Objectives: The objectives of the study were to determine: Knee valgus during the single leg squat, vertical drop jump, net shot and drop shot; Degree of internal or external rotation during the single leg squat, vertical drop jump, net shot and drop shot; Maximum knee flexion during the single leg squat, vertical drop jump and net shot. Methods: This case-control study included 14 participants with three ACL injury recovered athletes and 11 uninjured participants. The participants performed various functional tasks including vertical drop jump, single leg squat; the forehand net shot and the forehand drop shot. The data was analysed using the two-way ANOVA test, and the reliability of the data was evaluated using the Intra Class Coefficient. Results: The data showed a significant decrease in the range of knee rotation in ACL injured participants as compared to the uninjured cohort (F₇,₅₅₆=2.37; p=0.021). There was also a decrease in the maximum knee flexion angles and an increase in knee valgus angles in ACL injured participants although they were not statistically significant. Conclusion: There was a significant decrease in the knee rotation angles in the ACL injured participants which could be a potential cause for re-injury in these athletes in the future. Although the results for decrease in maximum knee flexion angles and increase in knee valgus angles were not significant, this may be due to a limited sample of ACL injured participants; there is potential for it to be identified as a variable of interest in the rehabilitation of ACL injuries. These changes in the knee biomechanics could be vital in the rehabilitation of ACL injured athletes in the future, and an inclusion of sports based tasks, e.g., Net shot along with standard protocol movements for ACL assessment would provide a better measure of the rehabilitation of the athlete.

Keywords: ACL, biomechanics, knee injury, racquet sport

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Authors: Tiffanie-Marie Borg, Yasmin Zeinolabediny, Nima Heidari, Ali Noorani, Mark Slevin, Angel Cullen, Stefano Olgiati, Alberto Zerbi, Alessandro Danovi, Adrian Wilson

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Knee Osteoarthritis (OA) is a critical cause of disability globally. In recent years, there has been growing interest in non-invasive treatments, such as intra-articular injection of micro-fragmented fat (MFAT), showing great potential in treating OA. Mesenchymal stem cells (MSCs), originating from pericytes of micro-vessels in MFAT, can differentiate into mesenchymal lineage cells such as cartilage, osteocytes, adipocytes, and osteoblasts. Secretion of growth factor and cytokines from MSCs have the capability to inhibit T cell growth, reduced pain and inflammation, and create a micro-environment that through paracrine signaling, can promote joint repair and cartilage regeneration. Here we have shown, for the first time, data supporting the hypothesis that women respond better in terms of improvements in pain and function to MFAT injection compared to men. Historically, women have been underrepresented in studies, and studies with both sexes regularly fail to analyse the results by sex. To mitigate this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. This observational, intention-to-treat study included the complete sample of 456 patients who agreed to be scored for pain (visual analogue scale (VAS)) and function (Oxford knee score (OKS)) at baseline regardless of subsequent changes to adherence or status during follow-up. We report that a significantly larger number of women responded to treatment than men: [90% vs. 60% change in VAS scores with 87% vs. 65% change in OKS scores, respectively]. Women overall had a stronger positive response to treatment with reduced pain and improved mobility and function. Pre-injection, our cohort of women were in more pain with worse joint function which is quite common to see in orthopaedics. However, during the 2-year follow-up, they consistently maintained a lower incidence of discomfort with superior joint function. This data clearly identifies a clear need for further studies to identify the cell and molecular biological and other basis for these differences and be able to utilize this information for stratification in order to improve outcome for both women and men.

Keywords: gender differences, micro-fragmented adipose tissue, knee osteoarthritis, stem cells

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Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

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Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

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Authors: Sarah F. M. Pilati, Carolina S. Flausino, Guilherme F. Hoffmeister, Davi R. Tames, Telmo J. Mezadri

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The effects that may be related to narghile smoking in the tissues of the oral cavity, trachea and lung and associated inflammation has been the question raised lately. The objective of this study was to identify histopathological changes and the presence of inflammation through the exposure of mice to narghile smoking through a whole-body study. The animals were divided in 4 groups with 5 animals in each group, being: one control group, one with 7 days of exposure, 15 days and the last one with 30 days. The animals were exposed to the conventional hookah smoke from Mizo brand with 0.5% percentage of unwashed tobacco and the EcOco brand coconut fiber having a dimension of 2cm × 2cm. The duration of the session was 30 minutes / day per 7, 15 and 30 days. The tobacco smoke concentration at which test animals were exposed was 35 ml every two seconds while the remaining 58 seconds were pure air. Afterward, the mice were sacrificed and submitted to histological evaluation through slices. It was found in the tongue of the 7-day group the presence in epithelium areas with acanthosis, hyperkeratosis and epithelial projections. In-depth, more intense inflammation was observed. All alteration processes increased significantly as the days of exposure increased. In trachea, with the 7-day group, there was a decrease in thickening of the pseudostratified epithelium and a slight decrease in lashes, giving rise to the metaplasia process, a process that was established in the 31-day sampling when the epithelium became stratified. In the conjunctive tissue, it was observed the presence of defense cells and formation of new vessels, evidencing the chronic inflammatory process, which decreased in the course of the samples due to the deposition of collagen fibers as seen in the 15 and 31 days groups. Among the structures of the lung, the study focused on the bronchioles and alveoli. From the 7-day group, intra-alveolar septum thickness increased, alveolar space decreased, inflammatory infiltrate with mononuclear and defense cells and new vessels formation were observed, increasing the number of red blood cells in the region. The results showed that with the passing of the days a progressive increase of the signs of changes in the region was observed, a factor that shows that narghile smoking stimulates alterations mainly in the alveoli (place where gas exchanges occur that should not present alterations) calling attention to the harmful and aggressive effect of narghile smoking. These data also highlighted the harmful effect of smoking, since the presence of acanthosis, hyperkeratosis, epithelial projections and inflammation evidences the cellular alteration process for the tongue tissue protection. Also, the narghile smoking stimulates both epithelial and inflammatory changes in the trachea, in addition to a process of metaplasia, a factor that reinforces the harmful effect and the carcinogenic potential of the narghile smoking.

Keywords: metaplasia, inflammation, pathological constriction, hyperkeratosis

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