Search results for: radionuclide therapy

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: N. Zandi, M. Sitarz, J. Jastrzebski, M. Vagheian, J. Choinski, A. Stolarz, A. Trzcinska

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¹³⁵La with the half-life of 19.5 h can be considered as a good candidate for Auger therapy. ¹³⁵La decays almost 100% by electron capture to the stable ¹³⁵Ba. In this study, all important possible reactions leading to ¹³⁵La production are investigated in details, and the corresponding theoretical yield for each reaction using the Monte-Carlo method (MCNPX code) are presented. Among them, the best reaction based on the cost-effectiveness and production yield regarding Poland facilities equipped with medical cyclotron has been selected. ¹³⁵La is produced using 16.5 MeV proton beam of general electric PET trace cyclotron through the ¹³⁵Ba(p,n)¹³⁵La reaction. Moreover, for a consistent facilitating comparison between the theoretical calculations and the experimental measurements, the beam current and also the proton beam energy is measured experimentally. Then, the obtained proton energy is considered as the entrance energy for the theoretical calculations. The production yield finally is measured and compared with the results obtained using the MCNPX code. The results show the experimental measurement and the theoretical calculations are in good agreement.

Keywords: efficient ¹³⁵La production, proton cyclotron energy measurement, MCNPX code, theoretical and experimental production yield

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Authors: Yang Wei, Xueyan Wang, Hui Zou

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Objective: Investigation the prevalence of menopausal symptoms in patients with allergic symptoms, evaluation of the effect of sex hormones combined with anti-allergic therapy in these patients. Method: Age of 45-65 years old women with allergic symptoms at the same time in gynecological-endocrinology clinic in our hospital were selected from Feb 1 to May 31, 2010, randomly. The patients were given oral estradiol valerate plus progestin pills combined with anti-allergy treatment and then evaluated twice a week and one month later. Evaluation criterion: Menopause Rating Scale (MRS) and the degree of clinical symptoms were used to evaluate menopause and allergy separately. Results: 1) There were 195 cases of patients with menopausal symptoms at the age. Their MRS were all over 15. 2) Among them 45 patients were with allergic symptom accounted for 23% which were diagnosed by allergic department. 3) Evaluated after one week: the menopausal symptoms were improved and MRS were less than or equal to 5 in all these patients; the skin symptom of allergic symptoms vanished completely. 4) Evaluated after one month: Menopause symptoms were improved steadily; other clinical symptoms of allergy were also improved or without recurrence. Conclusion: The incidence rate of menopausal women with clinical symptoms of allergic diseases is high and it needs attention. The effect of sex hormones combined with anti-allergic therapy is obvious.

Keywords: menopausal, allergy, sex hormone, anti-allergy treatment

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Authors: Rohan Bhasin

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Agrammatism in non-fluent Aphasia Cases can be defined as a language disorder wherein a patient can only use content words ( nouns, verbs and adjectives ) for communication and their speech is devoid of functional word types like conjunctions and articles, generating speech of with extremely rudimentary grammar . Past approaches involve Speech Therapy of some order with conversation analysis used to analyse pre-therapy speech patterns and qualitative changes in conversational behaviour after therapy. We describe this approach as a novel method to generate functional words (prepositions, articles, ) around content words ( nouns, verbs and adjectives ) using a combination of Natural Language Processing and Deep Learning algorithms. The applications of this approach can be used to assist communication. The approach the paper investigates is : LSTMs or Seq2Seq: A sequence2sequence approach (seq2seq) or LSTM would take in a sequence of inputs and output sequence. This approach needs a significant amount of training data, with each training data containing pairs such as (content words, complete sentence). We generate such data by starting with complete sentences from a text source, removing functional words to get just the content words. However, this approach would require a lot of training data to get a coherent input. The assumptions of this approach is that the content words received in the inputs of both text models are to be preserved, i.e, won't alter after the functional grammar is slotted in. This is a potential limit to cases of severe Agrammatism where such order might not be inherently correct. The applications of this approach can be used to assist communication mild Agrammatism in non-fluent Aphasia Cases. Thus by generating these function words around the content words, we can provide meaningful sentence options to the patient for articulate conversations. Thus our project translates the use case of generating sentences from content-specific words into an assistive technology for non-Fluent Aphasia Patients.

Keywords: aphasia, expressive aphasia, assistive algorithms, neurology, machine learning, natural language processing, language disorder, behaviour disorder, sequence to sequence, LSTM

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Authors: Michal Krecichwost, Zauzanna Miodonska, Pawel Badura

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The diagnosis of sigmatism is mostly based on the observation of articulatory organs. It is, however, not always possible to precisely observe the vocal apparatus, in particular in the oral cavity of the patient. Speech processing can allow to objectify the therapy and simplify the verification of its progress. In the described study the methodology for classification of incorrectly pronounced phoneme [s] is proposed. The recordings come from adults. They were registered with the speech recorder at the sampling rate of 44.1 kHz and the resolution of 16 bit. The database of pathological and normative speech has been collected for the study including reference assessments provided by the speech therapy experts. Ten adult subjects were asked to simulate a certain type of stigmatism under the speech therapy expert supervision. In the recordings, the analyzed phone [s] was surrounded by vowels, viz: ASA, ESE, ISI, SPA, USU, YSY. Thirteen MFCC (mel-frequency cepstral coefficients) and RMS (root mean square) values are calculated within each frame being a part of the analyzed phoneme. Additionally, 3 fricative formants along with corresponding amplitudes are determined for the entire segment. In order to aggregate the information within the segment, the average value of each MFCC coefficient is calculated. All features of other types are aggregated by means of their 75th percentile. The proposed method of features aggregation reduces the size of the feature vector used in the classification. Binary SVM (support vector machine) classifier is employed at the phoneme recognition stage. The first group consists of pathological phones, while the other of the normative ones. The proposed feature vector yields classification sensitivity and specificity measures above 90% level in case of individual logo phones. The employment of a fricative formants-based information improves the sole-MFCC classification results average of 5 percentage points. The study shows that the employment of specific parameters for the selected phones improves the efficiency of pathology detection referred to the traditional methods of speech signal parameterization.

Keywords: computer-aided pronunciation evaluation, sibilants, sigmatism diagnosis, speech processing

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Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

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Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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Authors: Bassam Band, Simon Freeman, Rohan Munir, Hisham Band

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Objective: To determine efficacy of facial physiotherapy provided for patients with facial nerve palsy. Design: Retrospective study Subjects: 54 patients diagnosed with Facial nerve palsy were included in the study after they met the selection criteria including unilateral facial paralysis and start of therapy twelve months after the onset of facial nerve palsy. Interventions: Patients received the treatment offered at a facial physiotherapy clinic consisting of: Trophic electrical stimulation, surface electromyography with biofeedback, neuromuscular re-education and myofascial release. Main measures: The Sunnybrook facial grading scale was used to evaluate the severity of facial paralysis. Results: This study demonstrated the positive impact of physiotherapy for patient with facial nerve palsy with improvement of 24.2% on the Sunnybrook facial grading score from a mean baseline of 34.2% to 58.2%. The greatest improvement looking at different causes was seen in patient who had reconstructive surgery post Acoustic Neuroma at 31.3%. Conclusion: The therapy shows significant improvement for patients with facial nerve palsy even when started 12 months post onset of paralysis across different causes. This highlights the benefit of this non-invasive technique in managing facial nerve paralysis and possibly preventing the need for surgery.

Keywords: facial nerve palsy, treatment, physiotherapy, bells palsy, acoustic neuroma, ramsey-hunt syndrome

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Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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Authors: Minakshi Jain, I. P. Singh

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Due to the era of outstanding technology and modern lifestyle, human beings are debasing their physical, psychological, and mental well-being. The effect of this leads to a trail of chronic diseases like anxiety, loneliness, and depression, especially in children and young adults. This is visible in individuals who suffer from clinical depression, which leads to impaired mood and distortion of cognition, particularly in children. The Members of the WHO European Region made a declaration to provisioning each child with access to healthy and safe environments by 2020, and the decision was taken at the Conference on Environment and Health in 2010 as an initiative to improve access to green spaces in cities which provides universal access for quality spaces for both social interaction and human well-being. In line with this, the paper aims to establish a prospective study on linking green spaces and CBT (Cognitive behavior therapy) in order to treat disorders with reference to children and young adults. A questionnaire was adopted to explore the possibility of green spaces as additive measures for the existing modes of therapy. The results adapted from the questionnaire show that certain species of vegetation have a significant effect in enhancing effective mental well-being.

Keywords: CBT, therapeutic gardens UCLA loneliness scale, anxiety, depression, green spaces, biophilia, environmental psychology

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Authors: Kathie Records, R. Jeanne Ruiz, Kimberly Ayers, Rebecca Pasillas

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Background: Preterm births of less than 37 weeks gestation occur disproportionately to Hispanics living along the U.S.-Mexico border. Prematurity has devastating and costly effects on children, families and the health care system. Few preventive interventions have been tested for this vulnerable group. Objectives: To present the modeling and pilot testing of the theory-based Mastery Lifestyle Intervention (MLI), designed to reduce and prevent PTB among Mexican American women (the terms Hispanics or Latinas will also be used to represent this group) living in the United States. Design and Methods: The conceptualization of the problem of preterm births and the available literature underpinning the mastery lifestyle intervention will be reviewed. The lifestyle intervention includes foundational components of problem solving therapy and acceptance and commitment therapy. Findings from implementation of a one-group pilot test and focus group evaluated the feasibility and acceptability of the MLI. Summary: Participants found the MLI to be feasible and acceptable, and reported perceiving improved health status and familial relationships. Suggestions were provided for modifications prior to efficacy testing. The MLI appears to be a theoretically and empirically grounded intervention that holds promise for preventing preterm births among Latinas.

Keywords: birth, Hispanic, intervention, stress

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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: Ananya Pal, Neelakshi Sarkar, Debraj Saha, Dipanwita Das, Subhashish Kamal Guha, Bibhuti Saha, Runu Chakravarty

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Presently, tenofovir disoproxil fumurate (TDF) is the most effective anti-viral agent for the treatment of hepatitis B virus (HBV) in individuals co-infected with HIV and HBV as TDF has activity to suppress both wild-type and lamivudine (3TC)-resistant HBV. However, suboptimal response to TDF was reported in HIV-HBV co-infected individuals with prior 3TC therapy from different countries recently. The incidence of 3TC-resistant HBV strains is quite high in HIV-HBV co-infected patients experiencing long-term anti-retroviral therapy (ART) in eastern India. In spite of this risk, most of the patients with long-term 3TC treatment are continued with the same anti-viral agent in this country. Only a few have received TDF in addition to 3TC in the ART regimen since TDF has been available in India for the treatment of HIV-infected patients in 2012. In this preliminary study, we investigated the virologic and biochemical parameters among HIV-HBV co-infected patients who are non-responders to 3TC treatment during the continuation of 3TC or TDF add-on to 3TC in their ART regimen. Fifteen HIV-HBV co-infected patients who experienced long-term 3TC (mean duration months 36.87 ± 24.08 months) were identified with high HBV viremia ( > 20,000 IU/ml) or harbouring 3TC-resistant HBV. These patients receiving ART from School of Tropical Medicine Kolkata, the main ART centre in eastern India were followed-up semi-annually for next three visits. Different virologic parameters including quantification of plasma HBV load by real-time PCR, detection of hepatitis B e antigen (HBeAg) by commercial ELISA and anti-viral resistant mutations by sequencing were studied. During three follow-up among study subjects, 86%, 47%, and 43% had 3TC-mono-therapy (mean treatment-duration 41.54±18.84, 49.67±11.67, 54.17±12.37 months respectively) whereas 14%, 53%, and 57% experienced TDF in addition to 3TC (mean treatment duration 4.5±2.12, 16.56±11.06, and 23±4.07 months respectively). Mean CD4 cell-count in patients receiving 3TC was tended to be lower during third follow-up as compared to the first and the second [520.67±380.30 (1st), 454.8±196.90 (2nd), and 397.5±189.24 (3rd) cells/mm3) and similar trend was seen in patients experiencing TDF in addition to 3TC [334.5±330.218 (1st), 476.5±194.25 (2nd), and 461.17±269.89 (3rd) cells/mm3]. Serum HBV load was increased during successive follow-up of patients with 3TC-mono-therapy. Initiation of TDF lowered serum HBV-load among 3TC-non-responders at the time of second visit ( < 2,000 IU/ml), interestingly during third follow-up, mean HBV viremia increased >1 log IU/ml (mean 3.56±2.84 log IU/ml). Persistence of 3TC-resistant double and triple mutations was also observed in both the treatment regimens. Mean serum alanine aminotransferase remained elevated in these patients during this follow-up study. Persistence of high HBV viraemia and 3TC-resistant mutation in HBV during the continuation of 3TC might lead to major public health threat in India. The inclusion of TDF in the ART regimen of 3TC non-responder HIV-HBV co-infected patients showed adverse treatment response in terms of virologic and biochemical parameters. Therefore, serious attention is necessary for proper management of long-term 3TC experienced HIV-HBV co-infected patients with high HBV viraemia or 3TC-resistant HBV mutants in India.

Keywords: HBV, HIV, TDF, 3TC-resistant

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Sasan Khademnematolahi, Kevine Kamga Silihe, Katarína Pružinská, Martina Chrastina, Elisabeth Louise Ndjengue Mindang, František Dráfi, Katarína Bauerová

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Background: In ethnomedicine, plant parts and compounds are traditionally utilized to treat many disorders. Azadirachta indica, known as Neem, has been traditionally used in medicinal practices. Neem has various pharmaceutical activities, such as antioxidant and anti-inflammatory, due to the content of bioactive compounds like nimbolide, azadirachtin, and gedunin.Through its effect on pathological inflammatory processes, supplementation with it could alleviate the symptoms of rheumatoid arthritis (RA). Methods: This research aimed to assess Neem seed oil's impact on rats with adjuvant arthritis. Three doses in monotherapy and two in combination with methotrexate (MTX) have been studied and their effect was compared. Neem p.o. doses of 100, 200, and 300 mg/kg and MTX p.o. doses of 0.3 mg/kg were examined. After clinical parameters assessment, biochemical analysis was performed in plasma. Results: During the acute phase of the experimental arthritis (Day21), levels of MMP-9, MCP-1 and cytokines IL-1beta and IL-17A were measured. The positive results of inflammatory mediators evaluation in plasma encourage additional analysis also in related tissues to prove if Neem seed oil can be used as an adjuvant therapy for RA. Conclusion: In this study, the combination therapy of Neem with MTX was most effective from all therapies investigated.

Keywords: adjuvant, neem, methotrexate, arthritis

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Authors: Oluwasina Folajinmi, Kate Ssamulla, Penninah Lutung, Daniel Reijer

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Background: Despite of well-verified benefits of anti-retroviral therapy (ART) in prolonging life expectancy being lost to follow-up (LTFU) presents a challenge to the success of ART programs in resource limited countries like Nigeria. In several studies of ART programs in developing countries, researchers have reported that there has been a high rate of LTFU among patients receiving care and treatment at ART treatment centers. This study seeks to determine the cause of LTFU among HIV clients. Method: A descriptive cross sectional study focused on a population of 9,280 persons living with HIV/AIDS who were enrolled in nine treatment centers in Nigeria (both pre-ART and ART patients were included). Out of the total population, 1752 (18.9%) were found to be LTFU. Of this group we randomly selected 1200 clients (68.5%) their d patients’ information was generated through a database. Data on demographics and CD4 counts, causes of LTFU were analyzed and summarized. Results: Out of 1200 LTFU clients selected, 462 (38.5%) were on ART; 341 clients (73.8%) had CD4 level < 500cell/µL and 738 (61.5%) on pre-ART had CD4 level >500/µL. In our records we found telephone number for 675 (56.1%) of these clients. 675 (56.1%) were owners of a phone. The majority of the client’s 731 (60.9%) were living at not more than 25km away from the ART center. A majority were females (926 or 77.2%) while 274 (22.8%) were male. 675 (56.1%) clients were reported traced via telephone and home address. 326 (27.2%) of clients phone numbers were not reachable; 173 (14.4%) of telephone numbers were incomplete. 71 (5.9%) had relocated due to communal crises and expert client trackers reported that some patient could not afford transportation to ART centers. Conclusion: This study shows that, low health education levels, poverty, relocations and lack of reliable phone contact were major predictors of LTFU. Periodic updates of home addresses, telephone contacts including at least two next of kin, phone text messages and home visits may improve follow up. Early and consistent tracking of missed appointments is crucial. Creation of more ART decentralized centres are needed to avoid long distances.

Keywords: anti-retroviral therapy, HIV/AIDS, predictors, lost to follow up

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Authors: Snezana Mugosa, Zoran Todorovic, Zoran Bukumiric, Ivan Radosavljevic, Natasa Djordjevic

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Introduction: Various studies have shown that the frequency of clopidogrel resistance ranges from 4-40%. The aim of this study was to provide in depth analysis of genetic and non-genetic factors that influence clopidogrel resistance in cardiology patients. Methods: We have conducted a prospective study in 200 hospitalized patients hospitalized at Cardiology Centre of the Clinical Centre of Montenegro. CYP2C19 genetic testing was conducted, and the PREDICT score was calculated in 102 out of 200 patients treated with clopidogrel in order to determine the influence of genetic and non-genetic factors on outcomes of interest. Adverse cardiovascular events and adverse reactions to clopidogrel were assessed during 12 months follow up period. Results: PREDICT score and CYP2C19 enzymatic activity were found to be statistically significant predictors of expressing lack of therapeutic efficacy of clopidogrel by multivariate logistic regression, without multicollinearity or interaction between the predictors (p = 0.002 and 0.009, respectively). Conclusions: Pharmacogenetics analyses that were done in the Montenegrin population of patients for the first time suggest that these analyses can predict patient response to the certain therapy. Stepwise approach could be used in assessing the clopidogrel resistance in cardiology patients, combining the PREDICT score, platelet aggregation test, and genetic testing for CYP2C19 polymorphism.

Keywords: clopidogrel, pharmacogenetics, pharmacotherapy, PREDICT score

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Fauziah Mohd Sa’ad, Mohammad Aziz Shah, B. Mohammad Arip, Norazani Ahmad, Mohd Noor Idris, Hapsah M. Yusof

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This study was carried out to assess the application of person-centred therapy and Cognitive Psychology Ad-Din group counseling on self-concept, depression, and resilience of teenage pregnancy. This study involved 55 teenage pregnancy at three women’s refuge centers which are from KEWAJA, Rhaidatus Sakinah, and Taman Seri Puteri Cheras (JKM). Subjects were classed into two treatment groups and one control group. The Multidimensional Self-Concept Scale (MSCS), Beck Depression inventory (BDI) and Adolescent Resiliency Attitude Scale (ARAS) was administered to assess self-concept, depression, and resilience of teenage pregnancy. The control pre and post test design was used for this study. The research data were analyzed using descriptive analysis, ANOVA, MANCOVA and Tuckey Post Hoc with the significant level of .01 and .05. All treatment group received group counseling sessions for 7 consecutive week, once in each week. The Person-centred group and Cognitive Psychology Ad-Din group counseling showed a significant reduction (pre-test to post-test) on depression, enhancing self-concept and resilience of teenage pregnancy.

Keywords: group counseling, person-centred therapy, cognitive psychology Ad-Din, teenage pregnancy

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Authors: Mary Butler

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Background: Screening programmes for older drivers in Europe (though not the UK), and in many states in the US and in Australia are based on medical assessment of fitness to drive. These programmes require physicians (including general practitioners) to carry out an assessment of fitness to drive in their offices. In 2006, New Zealand changed from doing on-road driving tests with all older drivers from the age of 80, to a screening programme that uses medical assessment of fitness to drive only. Aim: This study set out to understand the experience of New Zealand GPs as they manage the process of medical assessment of fitness to drive assessments for older people. In particular, it aimed to establish how GPs understand the role of specialist driving assessment and rehabilitation carried out by occupational therapists. Design and setting: The study used an interpretive descriptive approach to analyze data from ten interviews with GPs in New Zealand. Results: The results indicated that GPs lack understanding about how occupational therapists can assist their patients, and tend to refer only when there is a disagreement with the patient. Conclusion: There are problems with the medical assessment of fitness to drive carried out by GPs, and there is a need for a more comprehensive community approach to driving cessation. Patients, families and the multidisciplinary team all have a role in deciding when driving cessation should occur. Occupational therapists have a particular responsibility for strategic leadership in this area of practice.

Keywords: assessment, driving, older people, occupational therapy

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Authors: Maurizio Dapor, Isabel Abril, Pablo de Vera, Rafael Garcia-Molina

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The ionization yield of ion tracks in polymers and bio-molecular systems reaches a maximum, known as the Bragg peak, close to the end of the ion trajectories. Along the path of the ions through the materials, many electrons are generated, which produce a cascade of further ionizations and, consequently, a shower of secondary electrons. Among these, very low energy secondary electrons can produce damage in the biomolecules by dissociative electron attachment. This work deals with the calculation of the energy distribution of electrons produced by protons in a sample of polymethylmethacrylate (PMMA), a material that is used as a phantom for living tissues in hadron therapy. PMMA is also of relevance for microelectronics in CMOS technologies and as a photoresist mask in electron beam lithography. We present a Monte Carlo code that, starting from a realistic description of the energy distribution of the electrons ejected by protons moving through PMMA, simulates the entire cascade of generated secondary electrons. By following in detail the motion of all these electrons, we find the radial distribution of the energy that they deposit in PMMA for several initial proton energies characteristic of the Bragg peak.

Keywords: Monte Carlo method, secondary electrons, energetic ions, ion-beam cancer therapy, ionization cross section, polymethylmethacrylate, proton beams, secondary electrons, radial energy distribution

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Authors: Kavita Khoiwal, Vatsla Dadhwal, K. Aparna Sharma, Dipika Deka, Plabani Sarkar

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Introduction: About 2.4 million (1.93 - 3.04 million) people are living with HIV/AIDS in India. Of all HIV infections, 39% (9,30,000) are among women. 5.4% of infections are from mother to child transmission (MTCT), 25,000 infected children are born every year. Besides the risk of mother to child transmission of HIV, these women are at risk of the higher adverse pregnancy outcome. The objectives of the study were to compare the obstetric and neonatal outcome in women who are HIV positive with low-risk HIV negative women and effect of antiretroviral drugs on preterm birth and IUGR. Materials and Methods: This is a retrospective case record analysis of 212 HIV-positive women delivering between 2002 to 2015, in a tertiary health care centre which was compared with 238 HIV-negative controls. Women who underwent medical termination of pregnancy and abortion were excluded from the study. Obstetric outcome analyzed were pregnancy induced hypertension, HIV positive intrauterine growth restriction, preterm birth, anemia, gestational diabetes and intrahepatic cholestasis of pregnancy. Neonatal outcome analysed were birth weight, apgar score, NICU admission and perinatal transmission.HIV-positiveOut of 212 women, 204 received antiretroviral therapy (ART) to prevent MTCT, 27 women received single dose nevirapine (sdNVP) or sdNVP tailed with 7 days of zidovudine and lamivudine (ZDV + 3TC), 15 received ZDV, 82 women received duovir and 80 women received triple drug therapy depending upon the time period of presentation. Results: Mean age of 212 HIV positive women was 25.72+3.6 years, 101 women (47.6 %) were primigravida. HIV positive status was diagnosed during pregnancy in 200 women while 12 women were diagnosed prior to conception. Among 212 HIV positive women, 20 (9.4 %) women had preterm delivery (< 37 weeks), 194 women (91.5 %) delivered by cesarean section and 18 women (8.5 %) delivered vaginally. 178 neonates (83.9 %) received exclusive top feeding and 34 neonates (16.03 %) received exclusive breast feeding. When compared to low risk HIV negative women (n=238), HIV positive women were more likely to deliver preterm (OR 1.27), have anemia (OR 1.39) and intrauterine growth restriction (OR 2.07). Incidence of pregnancy induced hypertension, diabetes mellitus and ICP was not increased. Mean birth weight was significantly lower in HIV positive women (2593.60+499 gm) when compared to HIV negative women (2919+459 gm). Complete follow up is available for 148 neonates till date, rest are under evaluation. Out of these 7 neonates found to have HIV positive status. Risk of preterm birth (P value = 0.039) and IUGR (P value = 0.739) was higher in HIV positive women who did not receive any ART during pregnancy than women who received ART. Conclusion: HIV positive pregnant women are at increased risk of adverse pregnancy outcome. Multidisciplinary team approach and use of highly active antiretroviral therapy can optimize the maternal and perinatal outcome.

Keywords: antiretroviral therapy, HIV infection, IUGR, preterm birth

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Authors: Emanuela Zilli, Antonio Madia, Milvia Marchiori, Paola Anello, Chiara Cabbia, Emanuela Velo, Delia Campagnolo, Michele Scomazzon, Emanuela Salvatico, S. Tikvina, Antonio Miotti

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Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). Antiviral medicines can cure more than 95% of cases of hepatitis C infection, but access to diagnosis and treatment remains low. The ULSS 6 Euganea – Health Trust has implemented a campaign to eradicate hepatitis C in the province of Padua (North-East of Italy), which can be subdivided into three areas: North (300.000 inhabitants), Centre (400.000) and South (300.000). In September 2021, the project was launched in the Northern area; a set of brochures was distributed in outpatient services, general practitioners’ clinics and offices, community pharmacy services, social health districts, and through social networks. The Hepatology Service contacted 460 patients selected by the Clinical Laboratory (positivity for HCV antibodies): 83 patients (18.0%) had been already cured of HCV infection, missing or deceased; 377 patients (82.0%) met the criteria to be eligible for HCV eradication therapy and were therefore included in a Day Service specific agenda and followed by a multidisciplinary team of healthcare professionals, with a dedicated telephone line. Haemato-chemical tests, general medical check-ups and ultrasound tests with fibroscan were performed. Patients were tested for Sars-CoV-2 positivity; those not yet vaccinated against Covid-19 were encouraged to complete the vaccination scheme. All 377 patients (100%) received HCV eradication therapy at the community pharmacy service; a detailed explanation of how to take their medication was provided. At the end of the first phase, Covid-19 vaccination rate was 100% (377/377), including patients already vaccinated and new-vaccinated. Check-up appointments were arranged after 2 or 3 months, according to the treatment plan. The awareness campaign and the organization of HCV eradication therapy service by ULSS 6 Euganea are proving to be effective; the project is now going to be applied to Central and Southern areas of the province (1.132 patients).

Keywords: public health, HCV-eradication, Covid-19 emergency, health communication strategies

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Authors: Navah Z. Ratzon, Talia Glick, Iris Manor

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Attention Deficit Hyperactivity Disorder (ADHD) is a chronic disorder that affects the sufferer’s functioning throughout life and in various spheres of activity, including driving. Difficulties in cognitive functioning and executive functions are often part and parcel of the ADHD diagnosis, and thus form a risk factor in driving. Studies examining the effectiveness of intervention programs for improving and rehabilitating driving in typical teenagers have been conducted in relatively small numbers; while studies on similar programs for teenagers with ADHD have been especially scarce. The aim of the present study has been to examine the effectiveness of a metacognitive occupational therapy intervention program for reducing risk factors in driving among teenagers with ADHD. The present study included 37 teenagers aged 17 to 19. They included 23 teenagers with ADHD divided into experimental (11) and control (12) groups; as well as 14 non-ADHD teenagers forming a second control group. All teenagers taking part in the study were examined in the Tel Aviv University driving lab, and underwent cognitive diagnoses and a driving simulator test. Every subject in the intervention group took part in 3 assessment meetings, and two metacognitive treatment meetings. The control groups took part in two assessment meetings with a follow-up meeting 3 months later. In all the study’s groups, the treatment’s effectiveness was tested by comparing monitoring results on the driving simulator at the first and second evaluations. In addition, the driving of 5 subjects from the intervention group was monitored continuously from a month prior to the start of the intervention, a month during the phase of the intervention and another month until the end of the intervention. In the ADHD control group, the driving of 4 subjects was monitored from the end of the first evaluation for a period of 3 months. The study’s findings were affected by the fact that the ADHD control group was different from the two other groups, and exhibited ADHD characteristics manifested by impaired executive functions and lower metacognitive abilities relative to their peers. The study found partial, moderate, non-significant correlations between driving skills and cognitive functions, executive functions, and perceptions and attitudes towards driving. According to the driving simulator test results and the limited sampling results of actual driving, it was found that a metacognitive occupational therapy intervention may be effective in reducing risk factors in driving among teenagers with ADHD relative to their peers with and without ADHD. In summary, the results of the present study indicate a positive direction that speaks to the viability of using a metacognitive occupational therapy intervention program for reducing risk factors in driving. A further study is required that will include a bigger number of subjects, add actual driving monitoring hours, and assign subjects randomly to the various groups.

Keywords: ADHD, driving, driving monitoring, metacognitive intervention, occupational therapy, simulator, teenagers

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Authors: Bambi Ward

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Children of Holocaust survivors have been described as inheriting their parents’ trauma as a result of ‘vicarious memory’. The term refers to a process whereby second generation Holocaust survivors subconsciously remember aspects of Holocaust trauma, despite not having directly experienced it. This can occur even when there has been a conspiracy of silence in which survivors chose not to discuss the Holocaust with their children. There are still people born in various parts of the world such as Poland, Hungary, other parts of Europe, USA, Canada and Australia, who have only learnt of their Jewish roots as adults. This discovery may occur during a parent’s deathbed confession, or when an adult child is sorting through the personal belongings of a deceased family member. Some Holocaust survivors chose to deny their Jewish heritage and raise their children as Christians. Reasons for this decision include the trauma experienced during the Holocaust for simply being Jewish, the existence of anti-Semitism, and the desire to protect one’s self and one’s family. Although there has been considerable literature written about the transgenerational impact of trauma on children of Holocaust survivors, there has been little scholarly investigation into the effects of a hidden Jewish identity on these children. This paper presents a case study of an adult child of Hungarian Holocaust survivors who was raised as a Christian. At the age of eight she was told about her family’s Jewish background, but her parents insisted that she keep this a secret, even if asked directly. She honoured their request until she turned forty. By that time she had started the challenging process of reclaiming her Jewish identity. The paper outlines the tension between family loyalty and individual freedom, and discusses the role that art and art therapy played in assisting the subject of the case study to reclaim her Jewish identity and commence writing a memoir about her spiritual journey. The main methodology used in this case study is creative practice-led research. Particular attention is paid to the utilisation of an autoethnographic approach. The autoethnographic tools used include reflective journals of the subject of the case study. These journals reflect on the subject’s collection of autobiographical data relating to her family history, and include memories, drawings, products of art therapy, diaries, letters, photographs, home movies, objects, and oral history interviews with her mother. The case study illustrates how art and art therapy benefitted a second generation Holocaust survivor who was brought up having to suppress her Jewish identity. The process allowed her to express subconscious thoughts and feelings about her identity and free herself from the burden of the long term secret she had been carrying. The process described may also be of assistance to other traumatised people who have been trying to break the silence and who are seeking to express themselves in a positive and healing way.

Keywords: art, hidden identity, holocaust, silence

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Siobhan Hegarty, Michael Bloomfield, Kim Entholt, Dorothy Williams, Helen Kennerley

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Complex Post-Traumatic Stress Disorder (CPTSD) confers greater risk of poor outcomes than does Post-Traumatic Stress Disorder (PTSD). Despite this, the current treatment guidelines for CPTSD aim to reduce only the ‘core’ symptoms of re-experiencing, hyper-vigilance and avoidance, while not addressing the Disturbances of Self Organisation (DSO) symptoms that distinguish this novel diagnosis from PTSD. The Recovering from Child Abuse Programme (RCAP) is a group protocol, based on the principles of cognitive behavioural therapy (CBT). Preliminary evidence suggests the program is effective at reducing DSO symptoms. This pilot study is the first to investigate the potential effectiveness of the RCAP for the specific treatment of CPTSD. This study was conducted as a service evaluation in a secondary care, traumatic stress service. Treatment was delivered once a week, in two-hour sessions, to ten existing female CPTSD patients of the service, who had experienced sexual abuse in childhood. The programme was administered by two therapists and two additional facilitators, following the RCAP protocol manual. Symptom severity was measured before the administration of therapy and was tracked across a range of measures (International Trauma Questionnaire; Patient Health Questionnaire; Community Assessment of Psychic Experience; Work and Social Adjustment Scale) at five time points, over the course of treatment. Qualitative appraisal of the programme was gathered via weekly feedback forms and from audio-taped recordings of verbal feedback given during group sessions. Preliminary results suggest the programme causes a slight reduction in CPTSD and depressive symptom severity and preliminary qualitative analysis suggests that the RCAP is both helpful and acceptable to group members. Final results and conclusions will follow completed thematic analysis of results.

Keywords: Child sexual abuse, Cognitive behavioural therapy, Complex post-traumatic stress disorder, Recovering from child abuse programme

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Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok

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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.

Keywords: innovation of medical services, sport, obesity, innovation

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Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu

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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.

Keywords: assembly inhibitors, core protein, HCV, trans-complementation

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Authors: Sanaa Mekdad, Leenah Alsayed

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Pharmacists play an important role in the CDTM in the care of patients with heart failure (HF). CDTM allows specialized, dedicated clinical pharmacists in a formal agreement in collaborative practice with physicians. Thus, the aim of this study is to investigate the role of cardiology clinical pharmacists in CDTM in decreasing hospitalization and cost. We studied patients with left ventricular systolic dysfunction in a cluster-randomized selection in a tertiary care center. We allocated 296 patients to pharmacist intervention from 1480 patients. Results: With an acceptance rate of 86%, we documented 696 interventions carried out by clinical pharmacists in cardiology. The average intervention was 2.4 patients, and the admission after interventions decreased from 0.79 to. 0.24 (p value = 0.001). Conclusions: In HF CDTM, clinical pharmacists play a crucial role in enhancing medication management, patient education, and lifestyle modification of patients with chronic heart failure. These efforts improve patients' outcomes and lower costs by reducing hospitalization and other associated expenses.

Keywords: cardiology, medication management, heart failure, outpatient therapy, pharmacist-based services, chronic heart failure, heart failure recommendations, CDTM, Middle East, pharmacist-based services, quality of life, pharmacist

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