Search results for: drug delivery to the brain

Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

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Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

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Authors: Sreelekha Prakash, Yulong Gu

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Background: About 61% of adults surveyed across 25 states reported they had experienced at least one type of Adverse Childhood Experience (ACE) before 18 years of age. Relationships between ACEs and a variety of substance-related behaviors and behavioral health have been reported in previous studies. ACEs can have lasting, negative effects on health, well-being, as well as life opportunities such as education and job potential. Objectives: For the current research, the aim was to assess the factors affecting substance use behavior in young adults. The further onset of drug use and its association was analyzed with ACEs and mental health. Method: The young adults from a county in the north-eastern United States were invited to participate in an online questionnaire survey with prior consent through an IRB approved study. The Survey included questions related to social determinants of health, 10 item ACE questionnaire, and substance use related to Alcohol, Marijuana, Opioids, Stimulants, and other drugs. PHQ-9 questionnaire was used to assess cognitive health. Results: Data was analyzed for the 244 completed surveys {68% (165) were females, and 78% (190) were Whites}. The average age of the participants was 26.7 years, and approximately 80% were lifelong residents of the county or year-round residents. Of the respondents, 50% (122) were high school graduates with some college education, and 56% (136) had a full-time jobs. Past 30-day usage for alcohol was 76% (72), and marijuana was 28.4% (27). The data showed that the higher the ACE scores, the younger they start using any substance (p < 0.0001). The data for PHQ-9 and ACE scores showed that the higher the ACE score, the higher the PHQ-9 score, with a significant p-value (p 0.0001). The current data also showed a significant association with other drugs; marijuana use showed significance for 30 days of use (p 0.0001), stimulant use (0.0008), prescription drug misuse (0.01), and opioids (0.01). Conclusion: These findings further support the association between ACEs and initiation of drug use and its correlation with mental health symptoms. Promoting a safe and supportive environment for children and youth in their earlier ages can prevent the youth and young adults from the effects of drug use and create healthy living habits for young adults.

Keywords: subtance use, young adults, adverse childhood experience, PHQ-9

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Authors: M. J. Pourvaghar, Sh. Khoshemehry

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Adopting inappropriate body posture during addiction can cause muscular and skeletal deformities. This study is aimed at investigating the effects of a program of the selected corrective exercises on the kyphosis of addicted male patients. Materials and methods: This was a quasi-experimental study. This study has been carried out using the semi-experimental method. The subjects of the present study included 104 addicted men between 25 to 45 years of age. In 2014, these men were referred to one of the NA (Narcotic Anonymous) centres in Kashan in 2015. A total of 24 people suffering from drug withdrawal, who had abnormal kyphosis, were purposefully selected as a sample. The sample was randomly divided into two groups, experimental and control; each group consisted of 12 people. The experimental group participated in a training program for 12 weeks consisting of three 60 minute sessions per week. That includes strengthening, stretching and PNF exercises (deep stretching of the muscle). The control group did no exercise or corrective activity. The Kolmogorov-Smirnov test was used to assess normal distribution of data; and a paired t-test and covariance analysis test were used to assess the effectiveness of the exercises, with a significance level of P≤0.05 by using SPSS18. The results showed that three months of the selected corrective exercises had a significant effect (P≤ 0.005) on the correction of the kyphosis of the addicted male patients after three months of rehabilitation (drug withdrawal) in the experimental group, while there was no significant difference recorded in the control group (P≥0.05). The results show that exercise and corrective activities can be used as non-invasive and non-pharmacological methods to rehabilitate kyphosis abnormalities after drug withdrawal and treatment for addiction.

Keywords: kyphosis, exercise-rehabilitation, addict, addiction

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Authors: Larissa Burruano, Sergey Grabovyj, Irina Nguen

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The study aimed to assess the level of adherence to anti retroviral therapy (ART) and to examine the relationship between adherence and risk behavior factor (drug use) among patients infected with HIV. The patients with newly diagnosed or established HIV infection under follow-up at the Sumskij Regional Centre for AIDS Prevention in Ukraine were eligible for this study. Medical records were used to measure the patient’s adherence to medication. Measurements were obtained at month 6 and at month 12 to calculate the number of medication omission during the past 30 days: (on a 2-point scale – once until three in a month – were considered adherent, three and more in a month – were considered non-adherent). Of the 50 study participants, 27 (54.0%) were men and 23 (46.0%) women. The mean age is 35.2 years (SD= 5.1). A majority of the patients (82.0%) is in the age group of 25-30 years. The main level of adherence was 74.0% and 66.0% at 6 and 12 months, respectively. The main routes of HIV transmission were drug injection among men 12 (44.4%) and sexual contact among women 11 (47.8%). Univariate analyses indicated that patients who had lower level of education were more likely to have been non-adherent at month 6- (X2 =5.1, n=50, p < .05) and at month 12 (X2 = 4.34, n=50, p < .05). Multivariate tests showed that only age (OR= 1.163 [95% CI 0.98–1.370]) was significant independent predictor of treatment adherence, while gender, education, employment status were not predictive for the risk of developing non-compliance. There was not a significant interaction between non-adherence and intravenous drug use. Consistent with these findings, younger people were more likely to have missed a dose of their medication because they had a greater sense of invulnerability than older patients. The study indicates that the socio demographic characteristic should be taken into an account in the future research regarding adherence in the case of HIV infection. If the patient anti retroviral adherence can be improved by qualitatively better medical care in all regions of the Ukraine, behavioral changes in the population can to be expected in the long term.

Keywords: HIV, antiretroviral therapy, adherence, Ukraine, Eastern Europe

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Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

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Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

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Authors: E. Irankhah, M. Zarif, E. Mazrooei Rad, K. Ghandehari

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Alzheimer's prevalence is on the rise, and the disease comes with problems like cessation of treatment, high cost of treatment, and the lack of early detection methods. The pathology of this disease causes the formation of protein deposits in the brain of patients called plaque amyloid. Generally, the diagnosis of this disease is done by performing tests such as a cerebrospinal fluid, CT scan, MRI, and spinal cord fluid testing, or mental testing tests and eye tracing tests. In this paper, we tried to use the Medial Temporal Atrophy (MTA) method and the Leave One Out (LOO) cycle to extract the statistical properties of the three Fz, Pz, and Cz channels of ERP signals for early diagnosis of this disease. In the process of CT scan images, the accuracy of the results is 81% for the healthy person and 88% for the severe patient. After the process of ERP signaling, the accuracy of the results for a healthy person in the delta band in the Cz channel is 81% and in the alpha band the Pz channel is 90%. In the results obtained from the signal processing, the results of the severe patient in the delta band of the Cz channel were 89% and in the alpha band Pz channel 92%.

Keywords: Alzheimer's disease, image and signal processing, LOO cycle, medial temporal atrophy

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Authors: William Elnemer, Nauman Hussain, Samir Al-Ali, Henry Shu, Diane Ghanem, Babar Shafiq

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Introduction: The incidence of infection in open tibial shaft injuries varies depending on the severity of the injury, with rates ranging from 1.8% for Gustilo-Anderson type I to 42.9% for type IIIB fractures. The timely administration of antibiotics upon presentation to the emergency department (ED) is an essential component of fracture management, and evidence indicates that prompt delivery of antibiotics is associated with improved outcomes. The objective of this study is to identify factors that contribute to the expedient administration of antibiotics. Methods: This is a retrospective study of open tibial shaft fractures at an academic Level I trauma center. Current Procedural Terminology (CPT) codes identified all patients treated for open tibial shaft fractures between 2015 and 2021. Open fractures were identified by reviewing ED and provider notes, and with ballistic fractures were considered open. Chart reviews were performed to extract demographics, fracture characteristics, postoperative outcomes, time to operative room, time to antibiotic order, and delivery. Univariate statistical analysis compared patients who received early antibiotics (EA), which were delivered within one hour of ED presentation, and those who received late antibiotics (LA), which were delivered outside of one hour of ED presentation. A multivariate analysis was performed to investigate patient, fracture, and transport/ED characteristics contributing to faster delivery of antibiotics. The multivariate analysis included the dependent variables: ballistic fracture, activation of Delta Trauma, Gustilo-Andersen (Type III vs. Type I and II), AO-OTA Classification (Type C vs. Type A and B), arrival between 7 am and 11 pm, and arrival via Emergency Medical Services (EMS) or walk-in. Results: Seventy ED patients with open tibial shaft fractures were identified. Of these, 39 patients (55.7%) received EA, while 31 patients (44.3%) received LA. Univariate analysis shows that the arrival via EMS as opposed to walk-in (97.4% vs. 74.2%, respectively, p = 0.01) and activation of Delta Trauma (89.7% vs. 51.6%, respectively, p < 0.001) was significantly higher in the EA group vs. the LA group. Additionally, EA cases had significantly shorter intervals between the antibiotic order and delivery when compared to LA cases (0.02 hours vs. 0.35 hours, p = 0.007). No other significant differences were found in terms of postoperative outcomes or fracture characteristics. Multivariate analysis shows that a Delta Trauma Response, arrival via EMS, and presentation between 7 am and 11 pm were independent predictors of a shorter time to antibiotic administration (Odds Ratio = 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). Discussion: Earlier antibiotic delivery is associated with arrival to the ED between 7 am and 11 pm, arrival via EMS, and a coordinated Delta Trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to employ a coordinated Delta Trauma response. Hospital personnel should be attentive to the rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Keywords: antibiotics, emergency department, fracture management, open tibial shaft fractures, orthopaedic surgery, time to or, trauma fractures

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Authors: Ignacio Luis Ramirez, Brittney Holcomb

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This study examines attitudes toward sexual assault based on religious affiliation, religiosity, religious beliefs, attitude about sexual assault education, alcohol, and drug use. This study found respondents who identified themselves as Catholics had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than Baptists or Protestants. Respondents who indicated a greater problem with alcohol had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements. In reference to gender, males had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than females. The respondent’s religiosity and religious beliefs did not affect their attitudes toward sexual assault. Additionally, attitudes about sexual assault education and drug use did not affect attitudes toward sexual assault.

Keywords: sexual assault, religion, education, alcohol, drugs

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Authors: S. Boulenouar, A. Boukli Hacene, S. Brahmi

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Quality is an old concept but which recently became omnipresent in the society. It is a pledge of the well done job and therefore the satisfaction of the customer. Now, dispensing pharmacies seem to be held away from this approach. Officinal staff is called to dispense drugs. However this essential function is rarely studied and taken into account. To contribute to the good use of medicines and to reduce the dangers, it is important to consider the dispensation of drugs practised in the pharmacies. It is a both descriptive and retrospective study .The descriptive part is to conduct a survey near to the dispensary pharmacists. The retrospective section concentrates on the analysis of medicine prescriptions dispensed to patients. Following the survey that we carried out near the pharmacists of dispensary of the town of Oran, it appears that in majority, they are not inclined, by themselves, to take up the challenge of quality at the dispensary. The approach requires time and a motivation that pharmacists do not have for the moment. Efforts are still needed on the part of pharmacists, but also of authorities and organizations in charge of quality in the dispensary. At the end of this work, it seems to us that the implementation of a quality approach is part of our reflection on the added value of the pharmacist of dispensary in the drug chain.

Keywords: customer satisfaction, dispensary, dispensing of the drug, quality approach

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Authors: Juariah Salam Suryadi

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North coast (Pantura) line is known as a high-risk area related to reproductive health. This is because along the line, there are many food stalls and entertainment industries that at night the function changed to be sexual transaction areas. This business line also facilitate circulation and transaction of drug and substance abuse. The environment conditions can influence adolescents who live in this area. It is because of adolescence characteristics that has high curiosity and looking for their identities. Therefore, purposes of this study were to explore reproductive health behaviour of early adolescents who lived in Pantura line and to suggest intervention based on the adolescents reproductive health conditions. This study was conducted in November 2016 among the seventh-grade students of Pusakajaya Junior High School 1 and 2, Subang District. Number of respondents were 269 students (Male=135, Female=134). The students were interviewed using a semi-structured questionnaire. Some teachers also interviewed to complement the data. The quantitative data was analyzed with univariate analysis, while content analysis was used for the qualitative data. Findings of this study showed that 85,2% of male students were smoker. Most of them started smoking at elementary school. Male students who often drunk alcohol were about 25,2% and all of them initiated to drink at elementary school. There were about 21,5% of male students ever used drug and substance abuse. There were 54,6% of the students that confessed having a lover. Most of them were female students. Sexual behaviour that ever done with their lovers were: holding hands (37,4%), kissing (4%) and embracing (6,8%). Although all of the students claimed to have never had sexual intercourse, but 5,9% of them said that they had friends who have had sexual intercourse. Most of the students also had friends with negative characteristics. Their friends were smoker (82,2%), drinker (53,2%) and drug abuse (42%). Most of the students recognized that they took the risks behaviour to get pleasure with their peers. Information from the teachers indicated that most problem of male students were smoking and drug and substance abuse; while sexuality including unwanted pregnancies were reproductive problems of many female students. Therefore, It is recommended to enhance understanding of the adolescents about risks of unhealthy behaviour through continuing reproductive health education, both in school and out of school. Policy support to create positive social environment and adolescents friendly is also suggested.

Keywords: reproductive health, behaviour, early adolescents, pantura line

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Authors: Nor Jannah Mohd Sebri, Khairul Anuar Mat Amin

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Dication cross-linked gellan gum hydrogel loaded with Ibuprofen with excellent mechanical properties had been synthesized as potential candidate for non-toxic biocompatible polymer material in tissue engineering. The gellan gum hydrogel with 5% Ibuprofen had produced a slow release profile with total drug release time of 25 hours as a resulting low swelling value recorded at 22+0.5%. Its compressive strength, 200.13+21 kPa was highest of all other hydrogel ratio of 0.5% and 1.0% Ibuprofen incorporation. Young’s Modulus of the hydrogel with 5% Ibuprofen was recorded at 1.8+0.01 MPa, indicating good gel strength in which it is capable of withstanding a fair amount of subjected force during topical wound dressing application. Excellent mechanical properties, together with slow release profile, make the ibuprofen-loaded hydrogel a prospect candidate as biocompatible extracellular matrices in wound management.

Keywords: gellan gum, ibuprofen, slow drug release, hydrogel

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Authors: Mark Pizzato

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How do ideas, images, and emotions in stage-plays and videos affect us? Do they evoke a greater awareness (or cognitive reappraisal of emotions) through possible shifts between left-cortical, right-cortical, and subcortical networks? To address these questions, this presentation summarizes the research of various neuroscientists, especially Bernard Baars and others involved in Global Workspace Theory, Matthew Lieberman in social neuroscience, Iain McGilchrist on left and right cortical functions, and Jaak Panksepp on the subcortical circuits of primal emotions. Through such research, this presentation offers an ‘inner theatre’ model of the brain, regarding major hubs of neural networks and our animal ancestry. It also considers recent experiments, by Mario Beauregard, on the cognitive reappraisal of sad, erotic, and aversive film clips. Finally, it applies the inner-theatre model and related research to survey results of theatre students who read and then watched the ‘To be or not to be’ speech in 8 different video versions (from stage and screen productions) of William Shakespeare’s Hamlet. Findings show that students become aware of left-cortical, right-cortical, and subcortical brain functions—and shifts between them—through staging and movie-making choices in each of the different videos.

Keywords: cognitive reappraisal, Hamlet, neuroscience, Shakespeare, theatre

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Authors: Tin Yee Ling, Kavita Maravar, Ruzica Ardalic

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Background: Uterine torsion (UT) in pregnancy of more than 45-degree along the longitudinal axis is a rare occurrence, and the aetiology remains unclear. Case: A 34-year-old G2P1 woman with a history of one previous caesarean section presented at 36+2 weeks with sudden onset lower abdominal pain, syncopal episode, and tender abdomen on examination. She was otherwise haemodynamically stable. Cardiotocography showed a pathological trace with initial prolonged bradycardia followed by a subsequent tachycardia with reduced variability. An initial diagnosis of uterine dehiscence was made, given the history and clinical presentation. She underwent an emergency caesarean section which revealed a 180-degree UT along the longitudinal axis, with oedematous left round ligament lying transverse anterior to the uterus and a segment of large bowel inferior to the round ligament. Detorsion of uterus was performed prior to delivery of the foetus, and anterior uterine wall was intact with no signs of rupture. There were no anatomical uterine abnormalities found other than stretched left ovarian and round ligaments, which were repaired. Delivery was otherwise uneventful, and she was discharged on day 2 postpartum. Discussion: UT is rare as the number of reported cases is within the few hundreds worldwide. Generally, the uterus is supported in place by uterine ligaments, which limit the mobility of the structure. The causes of UT are unknown, but risk factors such as uterine abnormalities, increased uterine ligaments’ flexibility in pregnancy, and foetal malposition has been identified. UT causes occlusion of uterine vessels, which can lead to ischaemic injury of the placenta causing premature separation of the placenta, preterm labour, and foetal morbidity and mortality if delivery is delayed. Diagnosing UT clinically is difficult as most women present with symptoms similar to placenta abruption or uterine rupture (abdominal pain, vaginal bleeding, shock), and one-third are asymptomatic. The management of UT involves surgical detorsion of the uterus and delivery of foetus via caesarean section. Extra vigilance should be taken to identify the anatomy of the uterus experiencing torsion prior to hysterotomy. There have been a few cases reported with hysterotomy on posterior uterine wall for delivery of foetus as it may be difficult to identify and reverse a gravid UT when foetal well-being is at stake. Conclusion: UT should be considered a differential diagnosis of acute abdominal pain in pregnancy. It is crucial that the torsion is addressed immediately as it is associated with maternal and foetal morbidity and mortality.

Keywords: uterine torsion, pregnancy complication, abdominal pain, torted uterus

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Authors: Olga Maksakova

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A work with unconscious patients after acute brain damages besides special knowledge and practical skills of all the participants requires a very specific organization. A lot of said about team approach in neurorehabilitation, usually as for outpatient mode. Rehabilitologists deal with fixed patient problems or deficits (motion, speech, cognitive or emotional disorder). Team-building means superficial paradigm of management psychology. Linear mode of teamwork fits casual relationships there. Cases with deep altered states of consciousness (vegetative states, coma, and confusion) require non-linear mode of teamwork: recovery of consciousness might not be the goal due to phenomenon uncertainty. Rehabilitation team as Semi-open Complex System includes the patient as a part. Patient's response pattern becomes formed not only with brain deficits but questions-stimuli, context, and inquiring person. Teamwork is sourcing of phenomenology knowledge of patient's processes as Third-person approach is replaced with Second- and after First-person approaches. Here is a chance for real-time change. Patient’s contacts with his own body and outward things create a basement for restoration of consciousness. The most important condition is systematic feedbacks to any minimal movement or vegetative signal of the patient. Up to now, recovery work with the most severe contingent is carried out in the mode of passive physical interventions, while an effective rehabilitation team should include specially trained psychologists and psychotherapists. It is they who are able to create a network of feedbacks with the patient and inter-professional ones building up the team. Characteristics of ‘Team-Patient’ system (TPS) are energy, entropy, and complexity. Impairment of consciousness as the absence of linear contact appears together with a loss of essential functions (low energy), vegetative-visceral fits (excessive energy and low order), motor agitation (excessive energy and excessive order), etc. Techniques of teamwork are different in these cases for resulting optimization of the system condition. Directed regulation of the system complexity is one of the recovery tools. Different signs of awareness appear as a result of system self-organization. Joint meetings are an important part of teamwork. Regular or event-related discussions form the language of inter-professional communication, as well as the patient's shared mental model. Analysis of complex communication process in TPS may be useful for creation of the general theory of consciousness.

Keywords: rehabilitation team, urgent rehabilitation, severe brain damage, consciousness disorders, complex system theory

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Authors: Nerella Srinivas

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This study explores the significance of patent protection for artificial intelligence (AI) innovations in the pharmaceutical sector, emphasizing applications in drug discovery, personalized medicine, and clinical trial optimization. The challenges of patenting AI-driven inventions are outlined, focusing on the classification of algorithms as abstract ideas, meeting the non-obviousness standard, and issues around defining inventorship. The methodology includes examining case studies and existing patents, with an emphasis on how companies like Benevolent AI and Insilico Medicine have successfully secured patent rights. Findings demonstrate that a strategic approach to patent protection is essential, with particular attention to showcasing AI’s technical contributions to pharmaceutical advancements. Conclusively, the study underscores the critical role of understanding patent law and innovation strategies in leveraging intellectual property rights in the rapidly advancing field of AI-driven pharmaceuticals.

Keywords: artificial intelligence, pharmaceutical industry, patent protection, drug discovery, personalized medicine, clinical trials, intellectual property, non-obviousness

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Authors: Agnes Simone

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A 52-year-old male with unknown psychiatric and medical history was brought to the Psychiatric Emergency Room by ambulance directly from jail. He had been detained for three weeks for possession of a firearm while intoxicated. On initial evaluation, the patient was unable to provide a reliable history. He presented with odd jerking movements of his extremities and catatonic features, including mutism and stupor. His vital signs were stable. Patient was transferred to the medical emergency department for work-up of altered mental status. Due to suspicion for opioid overdose, the patient was given naloxone (Narcan) with no improvement. Laboratory work-up included complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, folate, magnesium, rapid plasma reagin, HIV, blood alcohol level, aspirin, and Tylenol blood levels, urine drug screen, and urinalysis, which were all negative. CT head and chest X-Ray were also negative. With this negative work-up, the medical team concluded there was no organic etiology and requested inpatient psychiatric admission. Upon re-evaluation by psychiatry, it was evident that the patient continued to have an altered mental status. Of note, the medical team did not include substance withdrawal in the differential diagnosis due to stable vital signs and a negative urine drug screen. The psychiatry team decided to check California's prescription drug monitoring program (CURES) and discovered that the patient was prescribed benzodiazepine alprazolam (Xanax) 2mg BID, a sedative-hypnotic, and hydrocodone/acetaminophen 10mg/325mg (Norco) QID, an opioid. After a thorough chart review, his daughter's contact information was found, and she confirmed his benzodiazepine and opioid use, with recent escalation and misuse. It was determined that the patient was experiencing alprazolam withdrawal, given this collateral information, his current symptoms, negative urine drug screen, and recent abrupt discontinuation of medications while incarcerated. After admission to the medical unit and two doses of alprazolam 2mg, the patient's mental status, alertness, and orientation improved, but he had no memory of the events that led to his hospitalization. He was discharged with a limited supply of alprazolam and a close follow-up to arrange a taper. Accompanying this case report, a qualitative review of presentations with alprazolam withdrawal was completed. This case and the review highlights: (1) Alprazolam withdrawal can occur at low doses and within just one week of use. (2) Alprazolam withdrawal can present without any vital sign instability. (3) Alprazolam withdrawal does not respond to short-acting benzodiazepines but does respond to certain long-acting benzodiazepines due to its unique chemical structure. (4) Alprazolam withdrawal is distinct from and more severe than other benzodiazepine withdrawals. This case highlights (1) the importance of physician utilization of drug-monitoring programs. This case, in particular, relied on California's drug monitoring program. (2) The importance of obtaining collateral information, especially in cases in which the patient is unable to provide a reliable history. (3) The importance of including substance intoxication and withdrawal in the differential diagnosis even when there is a negative urine drug screen. Toxidrome of withdrawal can be delayed. (4) The importance of discussing addiction and withdrawal risks of medications with patients.

Keywords: addiction risk of benzodiazepines, alprazolam withdrawal, altered mental status, benzodiazepines, drug monitoring programs, sedative-hypnotics, substance use disorder

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Authors: Shreya Borthakur, Aastha Vartak

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This Electroencephalogram (EEG) project on Rapid Visual Serial Processing (RSVP) paradigm explores the temporal dynamics of visual attention processing in response to rapidly presented visual stimuli. The study builds upon previous research that used real-world images in RSVP tasks to understand the emergence of object representations in the human brain. The objectives of the research include investigating the differences in accuracy and reaction times between 5 Hz and 20 Hz presentation rates, as well as examining the prominent brain waves, particularly alpha and beta waves, associated with the attention task. The pre-processing and data analysis involves filtering EEG data, creating epochs for target stimuli, and conducting statistical tests using MATLAB, EEGLAB, Chronux toolboxes, and R. The results support the hypotheses, revealing higher accuracy at a slower presentation rate, faster reaction times for less complex targets, and the involvement of alpha and beta waves in attention and cognitive processing. This research sheds light on how short-term memory and cognitive control affect visual processing and could have practical implications in fields like education.

Keywords: RSVP, attention, visual processing, attentional blink, EEG

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Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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Authors: Ugo Galvanetto, Pirto G. Pavan, Mirco Zaccariotto

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The discipline of Computer-integrated surgery (CIS) will provide equipment able to improve the efficiency of healthcare systems and, which is more important, clinical results. Surgeons and machines will cooperate in new ways that will extend surgeons’ ability to train, plan and carry out surgery. Patient specific CIS of the brain requires several steps: 1 - Fast generation of brain models. Based on image recognition of MR images and equipped with artificial intelligence, image recognition techniques should differentiate among all brain tissues and segment them. After that, automatic mesh generation should create the mathematical model of the brain in which the various tissues (white matter, grey matter, cerebrospinal fluid …) are clearly located in the correct positions. 2 – Reliable and fast simulation of the surgical process. Computational mechanics will be the crucial aspect of the entire procedure. New algorithms will be used to simulate the mechanical behaviour of cutting through cerebral tissues. 3 – Real time provision of visual and haptic feedback A sophisticated human-machine interface based on ergonomics and psychology will provide the feedback to the surgeon. The present work will address in particular point 2. Modelling the cutting of soft tissue in a structure as complex as the human brain is an extremely challenging problem in computational mechanics. The finite element method (FEM), that accurately represents complex geometries and accounts for material and geometrical nonlinearities, is the most used computational tool to simulate the mechanical response of soft tissues. However, the main drawback of FEM lies in the mechanics theory on which it is based, classical continuum Mechanics, which assumes matter is a continuum with no discontinuity. FEM must resort to complex tools such as pre-defined cohesive zones, external phase-field variables, and demanding remeshing techniques to include discontinuities. However, all approaches to equip FEM computational methods with the capability to describe material separation, such as interface elements with cohesive zone models, X-FEM, element erosion, phase-field, have some drawbacks that make them unsuitable for surgery simulation. Interface elements require a-priori knowledge of crack paths. The use of XFEM in 3D is cumbersome. Element erosion does not conserve mass. The Phase Field approach adopts a diffusive crack model instead of describing true tissue separation typical of surgical procedures. Modelling discontinuities, so difficult when using computational approaches based on classical continuum Mechanics, is instead easy for novel computational methods based on Peridynamics (PD). PD is a non-local theory of mechanics formulated with no use of spatial derivatives. Its governing equations are valid at points or surfaces of discontinuity, and it is, therefore especially suited to describe crack propagation and fragmentation problems. Moreover, PD does not require any criterium to decide the direction of crack propagation or the conditions for crack branching or coalescence; in the PD-based computational methods, cracks develop spontaneously in the way which is the most convenient from an energy point of view. Therefore, in PD computational methods, crack propagation in 3D is as easy as it is in 2D, with a remarkable advantage with respect to all other computational techniques.

Keywords: computational mechanics, peridynamics, finite element, biomechanics

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Authors: Mohd Taufiq bin Azmy, Yahaya Hassan, Shubashini Gnanasan, Loganathan Fahrni

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Inappropriate prescribing in older patients has been associated with resource utilization and adverse drug events (ADE) such as hospitalization, morbidity and mortality. Globally, there is a lack of published data on ADE induced by inappropriate prescribing. Our study is specific to an older population and is aimed at identifying risk factors for ADE and to develop a model that will link ADE to inappropriate prescribing. The design of the study was prospective whereby computerized medical records of 302 hospitalized elderly aged 65 years and above in 3 public hospitals in Malaysia (Hospital Serdang, Hospital Selayang and Hospital Sungai Buloh) were studied over a 7 month period from September 2013 until March 2014. Potentially inappropriate medications and potential prescribing omissions were determined using the published and validated START-STOPP criteria. Patients who had at least one inappropriate medication were included in Phase II of the study where ADE were identified by local expert consensus panel based on the published and validated Naranjo ADR probability scale. The panel also assessed whether ADE were causal or contributory to current hospitalization. The association between inappropriate prescribing and ADE (hospitalization, mortality and adverse drug reactions) was determined by identifying whether or not the former was causal or contributory to the latter. Rate of ADE avoidability was also determined. Our findings revealed that the prevalence of potential inappropriate prescribing was 58.6%. A total of ADEs were detected in 31 of 105 patients (29.5%) when STOPP criteria were used to identify potentially inappropriate medication; All of the 31 ADE (100%) were considered causal or contributory to admission. Of the 31 ADEs, 28 (90.3%) were considered avoidable or potentially avoidable. After adjusting for age, sex, comorbidity, dementia, baseline activities of daily living function, and number of medications, the likelihood of a serious avoidable ADE increased significantly when a potentially inappropriate medication was prescribed (odds ratio, 11.18; 95% confidence interval [CI], 5.014 - 24.93; p < .001). The medications identified by STOPP criteria, are significantly associated with avoidable ADE in older people that cause or contribute to urgent hospitalization but contributed less towards morbidity and mortality. Findings of the study underscore the importance of preventing inappropriate prescribing.

Keywords: adverse drug events, appropriate prescribing, health services research

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Authors: Md. Shadab, Mariyam N. Nashid, Venkata Srikanth Meka, Thiagarajan Madheswaran

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Naringenin (NAR), is a naturally occurring plant flavonoid, found predominantly in citrus fruits, that possesses a wide range of pharmacological properties including anti-oxidant, anti-inflammatory behaviour, cholesterol-lowering and anticarcinogenic activities. However, despite the therapeutic potential of naringenin shown in a number of animal models, its clinical development has been hindered due to its low aqueous solubility, slow dissolution rate and inefficient transport across biological membranes resulting in low bioavailability. Naringenin nanosuspension were produced using stabilizers Tween® 80 by high pressure homogenization techniques. The nanosuspensions were characterized with regard to size (photon correlation spectroscopy (PCS), size distribution, charge (zeta potential measurements), morphology, short term physical stability, dissolution profile and antioxidant potential. A nanocrystal PCS size of about 500 nm was obtained after 20 homogenization cycles at 1500 bar. The short-term stability was assessed by storage of the nanosuspensions at 4 ◦C, room temperature and 40 ◦C. Result showed that naringenin nanosuspension was physically unstable due to large fluctuations in the particle size and zeta potential after 30 days. Naringenin nanosuspension demonstrated higher drug dissolution (97.90%) compared to naringenin powder (62.76%) after 120 minutes of testing. Naringenin nanosuspension showed increased antioxidant activity compared to naringenin powder with a percentage DPPH radical scavenging activity of 49.17% and 31.45% respectively at the lowest DPPH concentration.

Keywords: bioavailability, naringenin, nanosuspension, oral delivery

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Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

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Authors: Anisur Rahman, Sabyasachi Behera, Pawan Pathak, Benazir Patil, Rajesh Khanna

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Background: Nearly half of India’s population is expected to reside in urban areas by 2030. The extent to which India's health system can provide for this large and growing city-based population will determine the country's success in achieving universal health coverage and improved national health indices. National Urban Health Mission (NUHM) strive for improving access to primary health care in urban areas. Implementation of NUHM solicits sensitive, effective and sustainable strategies to strengthen the service delivery mechanisms. The Challenge Initiative for Healthy Cities (TCIHC) is working with the Government of India and three provincial states to develop effective service delivery mechanisms for reproductive, maternal, newborn and child health (RMNCH) through a health systems approach for the urban poor. Method: A rapid assessment study was conceptualized and executed to generate evidence in order to address the challenges impeding in functioning of urban health facilities to deliver effective, efficient and equitable health care services in 7 cities spread across two project States viz. Madhya Pradesh and Odisha. Results: The findings of the assessment reflect: 1. The overall ecosystem pertaining to planning and management of public health interventions is not conducive. 2. The challenges regarding population dynamics like migration keeps on influencing the demand-supply-enabling environment triangle for both public and private service providers. 3. Lack of norms for planning and benchmark for service delivery further impedes urban health system as a whole. 4. Operationalization of primary level services have enough potential to meet the demand of slum dwellers at large. 5. Lack of policy driven strategies on how to integrate the NUHM with other thematic areas of Maternal, Newborn & Child Health (MNCH) and Family Planning (FP). 5. The inappropriate capacity building and acute shortage of Human Resources has huge implication on service provisioning and adherence to the service delivery protocols. Conclusion: The findings from rapid assessment are aimed to inform pertinent stakeholders to develop a multiyear city health action plan to strengthen the health systems in order to improve the efficacy of service delivery mechanism in urban settings.

Keywords: city health plan, health system, rapid assessment, urban mission

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Mojtaba Eshraghi Arani

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According to the international conventions for the carriage of goods by sea, the consignee is the person who is entitled to take delivery of the cargo from the carrier. Such a person is usually named in the relevant box of the bill of lading unless the latter is issued “To Order” or “To Bearer”. However, there are some cases in which the apparent consignee, as above, was not intended to take delivery of cargo, like the L/C issuing bank or the freight forwarder who are named as consignee only for the purpose of security or acceleration of transit process. In such cases as well as the BL which is issued “To Order”, the so-called “real consignee” can be found out in the “Notify Party” box. The dispute revolves around the choice between apparent consignee and real consignee for being entitled not only to take delivery of the cargo but also to sue the carrier for any damages or loss. While it is a generally accepted rule that only the apparent consignee shall be vested with such rights, some courts like France’s Cour de Cassation have declared that the “Notify Party”, as the real consignee, was entitled to sue the carrier and in some cases, the same court went far beyond and permitted the real consignee to take suit even where he was not mentioned on the BL as a “Notify Party”. The main argument behind such reasoning is that the real consignee is the person who suffered the loss and thus had a legitimate interest in bringing action; of course, the real consignee must prove that he incurred a loss. It is undeniable that the above-mentioned approach is contrary to the position of the international conventions on the express definition of consignee. However, international practice has permitted the use of BL in a different way to meet the business requirements of banks, freight forwarders, etc. Thus, the issue is one of striking a balance between the international conventions on the one hand and existing practices on the other hand. While the latest convention applicable for sea transportation, i.e., the Rotterdam Rules, dealt with the comparable issue of “shipper” and “documentary shipper”, it failed to cope with the matter being discussed. So a new study is required to propose the best solution for amending the current conventions for carriage of goods by sea. A qualitative method with the concept of interpretation of data collection has been used in this article. The source of the data is the analysis of domestic and international regulations and cases. It is argued in this manuscript that the judge is not allowed to recognize any one as real consignee, other than the person who is mentioned in the “Consingee” box unless the BL is issued “To Order” or “To Bearer”. Moreover, the contract of carriage is independent of the sale contract and thus, the consignee must be determined solely based on the facts of the BL itself, like “Notify Party” and not any other contract or document.

Keywords: real consignee, cargo, delivery, to order, notify the party

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Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Hesham Kozou

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Sensorineural hearing loss (SNHL) poses a significant challenge due to limited access to the inner ear for therapies. Emerging treatments such as regenerative, genetic, and pharmacotherapies offer hope for addressing this condition. This study aims to highlight the potential of cochlear implants and emerging therapies in managing sensorineural hearing loss by improving access to the inner ear. The study is conducted through a review of relevant literature and research articles in the field of cochlear implants and emerging therapies for hearing loss. It outlines how advancements in cochlear implant technologies, electrodes, and surgical techniques can facilitate the delivery of therapies to the inner ear, potentially revolutionizing the treatment of sensorineural hearing loss. The study underscores the potential of cochlear implants and emerging therapies in revolutionizing the treatment landscape for sensorineural hearing loss, emphasizing the feasibility of curing this condition by leveraging technological advancements.

Keywords: therapies for hearing loss management, future of CI as a cochlear delivery channel, regenerative, genetic and pharmacotherapeutic management of hearing loss

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Authors: Ritesh Verma, Manisha Rathi, Chand Singh Dhull, Sumit Sachdeva, Jitender Phogat

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A Rathke's cleft cyst is a benign growth found on the pituitary gland in the brain, specifically a fluid-filled cyst in the posterior portion of the anterior pituitary gland. It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40mm in diameter. A 38-year-old male presented to the outpatient department with loss of vision in the inferior quadrant of the left eye since 15 days. Visual acuity was 6/6 in the right eye and 6/9 in the left eye. Visual field analysis by HFA-24-2 revealed an inferior field defect extending to the supero-temporal quadrant in the left eye. MRI brain and orbit was advised to the patient and it revealed a well defined cystic pituitary adenoma indenting left optic nerve near optic chiasm consistent with the diagnosis of Rathke’s cleft cyst (RCC). The patient was referred to neurosurgery department for further management. Symptoms vary greatly between individuals having RCCs. RCCs can be non-functioning, functioning, or both. Besides headaches, neurocognitive deficits are almost always present but have a high rate of immediate reversal if the cyst is properly treated or drained.

Keywords: pituitary tumors, rathke’s cleft cyst, visual field defects, vision loss

Procedia PDF Downloads 205

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Mhaned Oubounyt, Jan Baumbach

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Differences in co-expression networks between two or multiple cells (sub)types across conditions is a pressing problem in single-cell RNA sequencing (scRNA-seq). A key challenge is to define those co-variations that differ between or among cell types and/or conditions and phenotypes to examine small regulatory networks that can explain mechanistic differences. To this end, we developed SCANet, an all-in-one Python package that uses state-of-the-art algorithms to facilitate the workflow of a combined single-cell GCN (Gene Correlation Network) and GRN (Gene Regulatory Networks) pipeline, including inference of gene co-expression modules from scRNA-seq, followed by trait and cell type associations, hub gene detection, co-regulatory networks, and drug-gene interactions. In an example case, we illustrate how SCANet can be applied to identify regulatory drivers behind a cytokine storm associated with mortality in patients with acute respiratory illness. SCANet is available as a free, open-source, and user-friendly Python package that can be easily integrated into systems biology pipelines.

Keywords: single-cell, co-expression networks, drug-gene interactions, co-regulatory networks

Procedia PDF Downloads 150