Search results for: hereditary breast-ovarian cancer syndrome

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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Authors: Mohamed M. Diab, Fahmy E. Mohamed, Alaa Balbaa

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Background: Myofascial pain syndrome a common type of non-articular musculoskeletal pain, is a condition associated with regional pain and muscle tenderness characterized by the presence of hypersensitive nodules. Objectives: the purpose of this study is to compare between the effects of manual progressive ischemic pressure versus the effect of post isometric facilitation in the treatment of Rhomboid latent myofascial trigger points. Methods: six patients had participated in this study. Patients divided into two groups. Group A treated by manual progressive ischemic pressure and traditional physical therapy program. Group B treated by post isometric facilitation and traditional physical therapy program. Treatment program was for 6 sessions over two week’s period. Result: Statistical analysis revealed that there is no significant difference in post treatment from pretreatment in pain severity (VAS) in myofascial trigger points with Rhomboid muscles) and Pain pressure threshold (PPT) for tenderness at both groups (A,B). Conclusion: ischemic pressure technique appear to be no more effective than post isometric facilitation in treatment of rhomboids latent myofacial trigger point.

Keywords: Rhmoiboid trigger point, myofacila trigger point, ischemic pressure, post isometric facilitation

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Authors: M. Roberts

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We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

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Authors: Waleed Jarjoura

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In various cases of visual impairments, the individuals are referred to expert Ophthalmologists in order to establish a correct diagnosis. Children with visual-impairments confront various challenging experiences in life since early childhood throughout lifespan. In some cases, blind infants, especially due to congenital hydrocephalus, suffer from high intra-cranial pressure and, consequently, go through a ventriculo-peritoneal shunt surgery in order to limit the neurological symptoms or decrease the cognitive impairments. In this article, a detailed description of numerous crucial implications of the V/P shunt surgery, through the right posterior-inferior parieto-temporal cortex, on the observed preliminary capabilities that are pre-requisites for the acquisition of literacy skills in braille, basic Math competencies, braille printing which suggest Gerstmann syndrome in the blind. In addition, significant difficultiesorientation and mobility skills using the Cane, in general, organizational skills, and social interactions were observed. The primary conclusion of this report focuses on raising awareness among neuro-surgeons towards the need for alternative intracranial routes for V/P shunt implantation in blind infants that preserve the right posterior-inferior parieto-temporal cortex that is hypothesized to modulate the tactual-spatial cues in braille discrimination. A second conclusion targets educators and therapists that address the acquired dysfunctionsin blind individuals due to V/P shunt surgeries.

Keywords: congenital blindness, hydrocephalus, shunt surgery, spatial orientation

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Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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Authors: Ofosuhene O. Apenteng, Noor Azina Ismail

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The human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) remains a global cause of morbidity and mortality. It has caused panic since its emergence. Relationships between migration and HIV/AIDS have become complex. In the absence of prospectively designed studies, dynamic mathematical models that take into account the migration movement which will give very useful information. We have explored the utility of mathematical models in understanding transmission dynamics of HIV and AIDS and in assessing the magnitude of how migration has impact on the disease. The model was calibrated to HIV and AIDS incidence data from Malaysia Ministry of Health from the period of 1986 to 2011 using Bayesian analysis with combination of Markov chain Monte Carlo method (MCMC) approach to estimate the model parameters. From the estimated parameters, the estimated basic reproduction number was 22.5812. The rate at which the susceptible individual moved to HIV compartment has the highest sensitivity value which is more significant as compared to the remaining parameters. Thus, the disease becomes unstable. This is a big concern and not good indicator from the public health point of view since the aim is to stabilize the epidemic at the disease-free equilibrium. However, these results suggest that the government as a policy maker should make further efforts to curb illegal activities performed by migrants. It is shown that our models reflect considerably the dynamic behavior of the HIV/AIDS epidemic in Malaysia and eventually could be used strategically for other countries.

Keywords: epidemic model, reproduction number, HIV, MCMC, parameter estimation

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Authors: John Angelo Labuguen, Sarah Joy Salvio

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Despite the low prevalence rate of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in the Philippines, the country is one of the seven countries in the world and the only country in Southeast Asia which reported an increasing trend in the number of people infected with HIV. Furthermore, people getting infected with HIV are becoming younger every year. Eighty-five percent (7,103) of the total number of youth (15-24 years old) with HIV were recorded in the past five years. The rising rates of HIV infection suggest the need to understand HIV knowledge, attitudes, and sexual behaviors among the youth in the Philippines. The University of the Philippines (UP), having a population that represents all regions of the country, can be reflective of the current situation of the Filipino youth in the issue of HIV/AIDS. This paper attempted to: (1) assess the level of knowledge on HIV/AIDS; (2) describe the attitude towards people living with HIV/AIDS; (3) identify socio-demographic and sexual behaviors associated with the level of HIV/AIDS knowledge; and (4) determine how knowledge on HIV/AIDS is related with attitude towards people living with HIV/AIDS among tertiary students of the UP Diliman. Self-administered survey was used to collect data from 308 randomly selected respondents. Data was encoded using CS Pro 6.2 and it was exported to SPSS v23 for further analysis. Findings of the study revealed that comprehensive correct knowledge on HIV/AIDS is associated with a somewhat accepting attitude towards PLWHA. Sociodemographic and sexual behavior characteristics do not contribute to the association between level of knowledge about HIV/AIDS and attitude towards PLWHA.

Keywords: attitude towards people living with HIV/AIDS, comprehensive HIV/AIDS knowledge, Philippines, university students

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Authors: Chien-Liang Chao, Yun-Sheng Lin

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Secondary metabolites are applied in the human life of the Chinese herbal medicine. Many drugs are originally extracted from natural products with combination of pharmaceutical and chemical studies. Crude extract of the leaves from Zamia furfureace L. has been shown to exhibit anticancer activities. The first chemical investigation of this plant was carried out by our group. In this study, four known compounds were isolated from Zamia furfureace L. with three lignins (Sesamin (1), Wodeshiol (2) and Paulownin (3)), and one dipeptide (Aurantiamide acetate (4)). The structures of these compounds were analyzed through the 1D-NMR(1H-NMR,13C-NMR)、2D-NMR(COSY、HMQC、HMBC、NOESY) spectroscopic analysis, and by comparison of variety of physical data (IR, mass spectrometry, ultraviolet, optical rotation). Among them, Aurantiamide acetate (4) exhibited weak cytotoxic activity against human gastric cancer cells.

Keywords: Zamia furfureace L., AGS, sesamin, Aurantiamide acetate, secondary metabolites

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Authors: Darshna Sharma, Suban K. Sahoo

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The detection of intracellular fluoride in human cancer cell HeLa was achieved by chemosensors derived from vitamin B6 cofactors using fluorescence imaging technique. These sensors were first synthesized by condensation of pyridoxal/pyridoxal phosphate with 2-amino(thio)phenol. The anion recognition ability was explored by experimental (UV-VIS, fluorescence and 1H NMR) and theoretical DFT [(B3LYP/6-31G(d,p)] methods in DMSO and mixed DMSO-H2O system. All the developed sensors showed both naked-eye detectable color change and remarkable fluorescence enhancement in the presence of F- and AcO-. The anion recognition was occurred through the formation of hydrogen bonded complexes between these anions and sensor, followed by the partial deprotonation of sensor. The detection limit of these sensors were down to micro(nano) molar level of F- and AcO-.

Keywords: chemosensors, fluoride, acetate, turn-on, live cells imaging, DFT

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Authors: Hossein Barri Ghazani

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Transfusion-related acute lung injury is the main reason of transfusion-related death, and it’s assigned to white blood cell reactive antibodies present in the blood product (anti-HLA class I and class II or anti granulocyte antibodies). TRALI may occur in the COVID-19 patients who are treated by convalescent plasma. The rate of TRALI’s reactions is the same in both males and females and can happen in all age groups. TRALI’s occurrence is higher for people who receive plasma from female donors because the parous female donors have multiple HLA antibodies in their plasma. Patients with chronic liver disease have an augmented risk of transfusion-related acute lung injuries from plasma containing blood products like FFP and PRP. The condition of TRALI suddenly starts with a non‐cardiogenic pulmonary Edema, often accompanied by marked systemic hypovolemic and hypotension. The conditions occur during or within a few hours of transfusion. Chest X-ray shows a nodular penetration or bats’ wing pattern of Edema which can be seen in acute respiratory distress syndrome as well. TRALI can occur with any type of blood products and can occur with as little as one unit. The blood donor center should be informed of the suspected TRALI reactions when the symptoms of TRALI are observed. After a review of the clinical data, the donors must be screened for granulocyte and HLA antibodies. The diagnosis and management of TRALI is not simple and is best done with a professional team and a specialty skilled nurse experienced with the upkeep of these patients.

Keywords: TRALI, transfusion-related death, anti-granulocyte antibodies, anti-HLA antibodies, COVID-19

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Authors: Chen-Yu Tsai, Wen-Te Liu, Chen-Chen Lo, Kang Lo, Yin-Tzu Lin

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Background: Driving drowsiness related to insufficient or disordered sleep accounts for a major percentage of vehicular accidents. Sleep deprivation is the primary reason related to low sleep efficiency. Nevertheless, the mechanism of sleep deprivation induces driving fatigue to remain unclear. Objective: The objective of this study is to associate the relationship between insufficient sleep efficiency and driving fatigue. Methodologies: The physical condition while driving was obtained from the questionnaires to classify the state of driving fatigue. Sleep efficiency was quantified as the polysomnography (PSG), and the sleep stages were sentenced by the reregistered Technologist during examination in a hospital in New Taipei City (Taiwan). The independent T-test was used to investigate the correlation between sleep efficiency, sleep stages ratio, and driving drowsiness. Results: There were 880 subjects recruited in this study, who had been done polysomnography for evaluating severity for obstructive sleep apnea syndrome (OSAS) as well as completed the driver condition questionnaire. Four-hundred-eighty-four subjects (55%) were classified as fatigue group, and 396 subjects (45%) were served as the control group. The ratio of stage three sleep (N3) (0.032 ± 0.056) in fatigue group were significantly lower than the control group (p < 0.01). The significantly higher value of snoring index (242.14 ± 205.51 /hours) was observed in the fatigue group (p < 0.01). Conclusion: We observe the considerable correlation between deep sleep reduce and driving drowsiness. To avoid drowsy driving, the sleep deprivation, and the snoring events during the sleeping time should be monitored and alleviated.

Keywords: driving drowsiness, sleep deprivation, stage three sleep, snoring index

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Authors: Lucia Salvioni, Pietro Giorgio Lovaglio, Valerio Leoni, Miriam Colombo, Luisa Fiandra

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The involvement of plasmatic surfactant protein-D (SP-D) in pulmonary diseases has been long investigated, and over the last two years, more interest has been directed to determine its role as a marker of COVID-19. In this direction, several studies aimed to correlate pulmonary surfactant proteins with the clinical manifestations of the virus indicated SP-D as a prognostic biomarker of COVID-19 pneumonia severity. The present work has performed a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (Lombardia, Italy) with the aim to assess differences in the hematic SP-D concentrations among COVID-19 patients and healthy donors and the role of SP-D as a prognostic marker of severity and/or of mortality risk. The obtained results showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors, so as between dead and survived patients. SP-D values were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. SP-D levels at admission and increasing differences among follow-up and admission values resulted in the strongest significant risk factors of mortality. Therefore, this study demonstrated the role of SP-D as a predictive marker of SARS-CoV-2 infection and its outcome. A significant correlation of SP-D with patient mortality indicated that it is also a prognostic factor in terms of mortality, and its early detection should be considered to design adequate preventive treatments for COVID-19 patients.

Keywords: SARS-CoV-2 infection, COVID-19, surfactant protein-D (SP-D), mortality, biomarker

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Authors: Oluwole Durodolu

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The rationale for this study is to explore the adaptive strategy that librarians adopt in performing night shifts in a mega-city like Lagos state. Maslach Burnout Theory would be used to measure the three proportions of burnout in understanding emotional exhaustion, depersonalisation, and individual accomplishment to scrutinise job-related burnout syndrome allied with longstanding, unsolved stress. The qualitative methodology guided by a phenomenological research paradigm, which is an approach that focuses on the commonality of real-life experience in a particular group, would be used, focus group discussion adopted as a method of data collection from library staff who are involved in night-shift. The participant for the focus group discussion would be selected using a convenience sampling technique in which staff at the cataloguing unit would be included in the sample because of the representative characteristics of the unit. This would be done to enable readers to understand phenomena as it is reasonable than from a remote perspective. The exploratory interviews which will be in focus group method to shed light on issues relating to security, housing, transportation, budgeting, energy supply, employee duties, time management, information access, and sustaining professional levels of service and how all these variables affect the productivity of all the 149 library staff and their work-life balance.

Keywords: nightshift, work-life balance, mega-city, academic library, Maslach Burnout Theory, Lagos State, University of Lagos

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Authors: Elmira Davasaz Tabrizi, Mushteba Sevil, Ercan Arican

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Directly or indirectly, the human microbiome, or the population of bacteria and other microorganisms living in the human body, has been linked with human health. Various research has examined the connection with both illness status and the composition of the human microbiome, even though current studies indicate that the gut microbiome influences the mucosa and immune system. A significant amount of effort is being put into understanding the human microbiome's natural history in terms of health outcomes while also expanding our comprehension of the molecular connections between the microbiome and the host. To maintain health and avoid disease, these efforts ultimately seek to find efficient methods for recovering human microbial communities. This review article describes how the human microbiome leads to chronic diseases and discusses evidence for an important significant disorder that is related to the microbiome and linked to prostate cancer: chronic prostatitis (CP).

Keywords: urobiome, chronic prostatitis, metagenomic, urinary microbiome

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Authors: Fernando Duarte

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The work aims to evaluate the use of classical image processing methodologies towards skin tone classification in dermatological images. The skin tone is an important attribute when considering several factor for skin cancer diagnosis. Currently, there is a lack of clear methodologies to classify the skin tone based only on the dermatological image. In this work, a recent released dataset with the label for skin tone was used as reference for the evaluation of classical methodologies for segmentation and adjustment of color space for classification of skin tone in dermatological images. It was noticed that even though the classical methodologies can work fine for segmentation and color adjustment, classifying the skin tone without proper control of the aquisition of the sample images ended being very unreliable.

Keywords: segmentation, classification, color space, skin tone, Fitzpatrick

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Authors: Imad Buishi, Almabrouk Fares, Hallowma Helmi

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Infection with verocytotoxin-producing Escherichia coli O157 in humans can lead to mild or bloody diarrhea with the hemolytic uremic syndrome (HUS) as a possible complication. Cattle appear to be important reservoirs for VTEC O157. Epidemiologic studies on the prevalence of VTEC O157 in dairy cattle in Libya have never been conducted. To investigate the prevalence and the risk factors associated with VTEC O157 on dairy farms in Tripoli region, fecal samples from 200 apparently healthy cows were collected once from 15 randomly selected dairy farms in the period July 2010 through September 2010. All fecal samples were examined for the prevalence of VTEC O157 by conventional plating using Sorbitol-MacConkey agar (SMAC). Isolated of E. coli were subjected to slide agglutination test using E. coli O157 antiserum. The results pointed out that the prevalence within-herd and among herds were 9% and 60% respectively. The prevalence of VTEC O157 in fecal samples of dairy cattle was significantly associated with husbandry practices on farm-level such as signs of diarrhoea (p=0.02, OR=3.2) and sharing water trough (p= 0.03, OR=3.0). It was concluded that dairy cattle in Tripoli area are important reservoirs of VTEC O157 strains that are potentially pathogenic for humans. When aiming at reducing risks for human by intervention at farm-level, it is of importance to reduce the number of positive animals and farms. For this, more research is needed to devise mitigation strategies that will reduce the on-farm contamination of VTEC O157.

Keywords: VTEC O157, prevalence, dairy cattle, tripoli

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Nayera E. Hassan, Sahar A. El-Masry, Mones M. Abu Shady, Rokia A. El Banna, Muhammad Al-Tohamy, Mehrevan M. Abd El-Moniem, Mona Anwar

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Circulating oxidized LDL (ox-LDL) is associated with obesity, insulin resistance (HOMA), metabolic syndrome, and cardiovascular disease in adults. Little is known about relations in children. Aim: To assess association of ox-LDL with fat distribution and insulin resistance in a group of obese Egyptian children. Methods: Study is cross-sectional consisting of 68 obese children, with a mean age of 9.96 ± 1.32. Each underwent a complete physical examination; blood pressure (SBP, DBP) and anthropometric measurements (weight, height, BMI; waist, hip circumferences, waist/hip ratio), biochemical tests of fasting blood glucose (FBS), insulin levels; lipid profile (TC, LDL,HDL, TG) and ox-LDL; calculated HOMA. Sample was classified according to waist/hip ratio into: group I with and group II without central obesity. Results: ox-LDL showed significant positive correlation with LDL and TC in all groups of obesity. After adjustment for age and sex, significant positive correlation was detected between ox-LDL with SBP, DBP, TC, LDL, insulin, and HOMA in group II and with TC and FBS in group I. Insignificant association was detected between ox-LDL and other anthropometric parameters including BMI in any group of obese children (p > 0.05). Conclusions: ox-LDL, as a marker of oxidative stress is not correlated with BMI among all studied obese children (aged 6-12 years). Increased oxidative stress has causal effects on insulin resistance in obese children without central obesity and on fasting blood sugar in those with central obesity. These findings emphasize the importance of obesity during childhood and suggest that the metabolic complications of obesity and body fat distribution are detectable early in life.

Keywords: ox-LDL, obesity, insulin resistance, children

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Authors: Bing Yan

Abstract:

Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no standard safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells1, perturb cellular signaling pathways2, affect various cell functions3, and cause malfunctions in animals4,5. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change their biological properties significantly. We modified nanoparticle surface using nano-combinatorial chemistry library approach6. Novel nanoparticles were discovered to exhibit significantly reduced toxicity6,7, enhance cancer targeting ability8, or re-program cellular signaling machineries7. Using computational chemistry, quantitative nanostructure-activity relationship (QNAR) is established and predictive models have been built to predict biocompatible nanoparticles.

Keywords: nanoparticle, nanotoxicity, nano-bio, nano-combinatorial chemistry, nanoparticle library

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Authors: Treder Natalia, Siemiński Mariusz

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Takotsubo cardiomyopathy (TC) is a recently defined clinical entity. First described by Japanese researchers, today is diagnosed worldwide in 1-2% of patients admitted with the preliminary diagnosis of Acute Coronary Syndrome. The etiology of takotsubo cardiomyopathy remains still largely unknown. Currently, the most likely cause of takotsubo is direct cytotoxicity caused by catecholamine surge triggered by emotional stress. There is a strong relation between recent severe emotional stress and TC. The aim of this study was to analysis the role of stress and personality as a risk factor of TT. The presented research involves 35 people who are diagnosed TC. All patients were women, mean age 60 years. The methods used in the research are popular psychological tests: Perceived Stress Scale, DS14 scale to measure type D personality, The Neo-Five Factor Inventory of Personality and psychological interview. The obtained results prove that stress events may directly precede or even release TC. The stressful events occurred directly before the symptoms in 75% examined. 65% assessed their family life as very stressful. Examiners have also a high level of experienced stress. Only 25% of the TC were classified as having type D personality but they have a high level of negative affectivity. The subjects had a high level of extraversion, openness to experiences and an average level of neuroticism. The results suggested that such a type of personality profile may predispose to the development of takotsubo cardiomyopathy. Patients with TT are the individuals who reveal joint tendency to the experience of negative emotions and very stressful family life.

Keywords: stress, personality trails, familiar problems, Takotsubo cardiomyopathy

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Authors: Abdol-Hassan Doulah

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In this research, some of the inorganic complexes of uranyl with N- donor ligands were synthesized. Complexes were characteriezed by FT-IR and UV spectra, ¹HNMR, ¹³CNMR and some physical properties. The uranyl unit (UO2) is composed of a center of uranium atom with the charge (+6) and two oxygen atom by forming two U=O double bonds. The structure is linear (O=U=O, 180) and usually stable. So other ligands often coordinate to the U atom in the plane perpendicularly to the O=U=O axis. The antitumor activity of some of ligand and their complexes against a panel of human tumor cell lines (HT29: Haman colon adenocarcinoma cell line T47D: human breast adenocarcinoma cell line) were determined by MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay. These data suggest that some of these compounds provide good models for the further design of potent antitumor compounds.

Keywords: inorganic, uranyl complex-donor ligands, Schiff bases, anticancer activity

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Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

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Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

Abstract:

The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: Marzieh Yassin, Fereshteh Navaee, Javad Sarrafzadeh, Reza Salehi

Abstract:

Introduction: Myofascial trigger point (MTrP) is one of the most common sources of musculoskeletal pain. Approximately 30-85% of the patients with musculoskeletal pains would experience MTrP in their life. The prevalence of MTrP has reported in the patients seen in a general orthopedic clinic, general medical clinic and specialty pain management centers, 21%, 30% and 93% respectively. Nowadays, dry needling is suggested as a standard treatment for MTrPs. The purpose of the present study was to examine the effectiveness of dry needling with stretching upper trapezius muscle on pain and pain pressure threshold in participants with active myofascial trigger point. Methods: Thirty participants with an active myofascial trigger point of the upper trapezius muscle were randomly divided into two groups: dry needling with passive stretch (n=15) and passive stretch alone (n=15). They received 5 sessions of the treatments for three weeks. The outcomes were pain intensity and pain pressure threshold that were assessed with visual analogue scale and algometer respectively. Results: Significant improvement in pain and pain pressure threshold was observed in both groups (P=0.0001) after the treatment. Also, the results showed a significant difference in measurements between two groups (P<0.05). Conclusion: Dry needling with passive stretch can be more effective on pain and pain pressure threshold than passive stretching alone in short term in participants with active myofascial trigger points.

Keywords: dry needling, myofascial pain syndrome, myofascial trigger point, stretching

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Authors: Jaiden X. Schraut

Abstract:

Medical Imaging Segmentation of Chest X-rays is used for the purpose of identification and differentiation of lung cancer, pneumonia, COVID-19, and similar respiratory diseases. Widespread application of computer-supported perception methods into the diagnostic pipeline has been demonstrated to increase prognostic accuracy and aid doctors in efficiently treating patients. Modern models attempt the task of segmentation and classification separately and improve diagnostic efficiency; however, to further enhance this process, this paper proposes a multi-output network that follows a U-Net architecture for image segmentation output and features an additional CNN module for auxiliary classification output. The proposed model achieves a final Jaccard Index of .9634 for image segmentation and a final accuracy of .9600 for classification on the COVID-19 radiography database.

Keywords: chest X-ray, deep learning, image segmentation, image classification

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Authors: Ilirian Laçi, Alketa Spahiu

Abstract:

Modality of treatment in hepatocellular carcinoma (HCC) patients depends on the stage of the disease. The Barcelona Clinic Liver Cancer Classification (BCLC) is the preferred staging system. There are many patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. The differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Because of these differences, not all patients benefit equally from TACE. Several tools have been devised to aid the decision-making process, which have shown promising initial results but have failed external evaluation and have not been translated to the clinic aspects. Criteria for treatment decisions in daily clinical practice are needed in all stages of the disease.

Keywords: hepatocellular carcinoma, transarterial chemoembolization, TACE, liver

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Authors: Kakali Bhadra

Abstract:

Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

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Authors: Sirikwan Ponprateep, Anchalee Tassanakajon, Vichien Rimphanitchayakit

Abstract:

A Kazal-type serine proteinase inhibitor, SPIPm2, was abundantly expressed in the hemocytes and secreted into shrimp plasma has anti-viral property against white spot syndrome virus (WSSV). To discover the molecular mechanism of antiviral activity, the binding assay showed that SPIPm2 bind to the components of viral particle and shrimp hemocyte. From our previous report, viral target protein of SPIPm2 was identified, namely WSV477 using yeast two-hybrid screening. WSV477 is an early gene product of WSSV and involved in viral propagation. In this study, the co-immunoprecipitation technique and Tandem Mass Spectrometry (LC-MS/MS) was used to identify the target protein of SPIPm2 from shrimp hemocyte. The target protein of SPIPm2 was cyclophilin A. In vertebrate, cyclophilin A or peptidylprolyl isomerase A was reported to be the immune suppressor interacted with cyclosporin A involved in immune defense response. The recombinant cyclophilin A from Penaeus monodon (rPmCypA) was produced in E.coli system and purified using Ni-NTA column to confirm the protein-protein interaction. In vitro pull-down assay showed the interaction between rSPIPm2 and rPmCypA. To study the biological function of these proteins, the expression analysis of immune gene in shrimp defense pathways will be investigated after rPmCypA administration.

Keywords: cyclophilin A, protein-protein interaction, Kazal-type serine proteinase inhibitor, Penaeus monodon

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Authors: Akankunda Veronicah Karuhanga

Abstract:

Dementia is an age mental disorder that makes victims lose normal functionality that needs delicate attention. It has been technically defined as a clinical syndrome that presents a number of difficulties in speech and other cognitive functions that change someone’s behaviors and can also cause impairments in activities of daily living, not forgetting a range of neurological disorders that bring memory loss and cognitive impairment. Family members are the primary healthcare givers and therefore, the way how they handle the situation in its early stages determines future deterioration syndromes like total memory loss. Unfortunately, most family members are ignorant about this condition and in most cases, the patients are brought to our facilities when their condition was already mismanaged by family members and we thus cannot do much. For example, incontinence can be managed at early stages through potty training or toilet scheduling before resorting to 24/7 diapers which are also not good. Professional Elderly care should be understood and practiced as an extension of homes, not a dumping place for people considered “abnormal” on account of ignorance. Immediate relatives should therefore be sensitized concerning the normalcy of dementia in the context of old age so that they can be understanding and supportive of dementia patients rather than discriminating against them as present-day lepers. There is a need to skill home-based caregivers on how to handle dementia in its early stages. Unless this is done, many of our elderly homes shall be filled with patients who should have been treated and supported from their homes. This skilling of home-based caregivers is a vital intervention because until elderly care is appreciated as a human moral obligation, many transactional rehabilitation centers will crop up and this shall be one of the worst moral decadences of our times.

Keywords: dementia, family, Alzheimers, relevancy

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Authors: Donna-Marie Phyllis Lanton

Abstract:

Sarcopenia is a well-known geriatric syndrome characterized by the progressive and generalized loss of muscle quantity or quality. The incidence of sarcopenia increases with age and is associated with adverse outcomes such as the increased risk of falls, cognitive impairment, loss of independence, diminished quality of life, increased health costs, need for care in a skilled nursing facility, and increased mortality. Physical activity, including resistance training, is the most prevalent recommendation for treating and preventing sarcopenia. Residents (N = 23) of a skilled nursing facility in East Orlando, Florida, participated in a 90-day strength training program designed using the PARIHS framework to improve measures of muscle mass, muscle strength, physical performance, and quality of life. Residents engaged in both resistance and balance exercises for 1 hour two times a week. Baseline data were collected and compared to data at Days 30, 60, and 90. T tests indicated significant gains on all measures from baseline to 90 days: muscle mass increased by 1.2 (t[22] = 2.85, p = .009), grip strength increased by 4.02 (t[22] = 8.15, p < .001), balance increased by 2.13 (t[22] = 18.64, p < .001), gait speed increased by 1.83 (t[22] = 17.84, p < .001), chair speed increased 1.87 (t[22] = 16.36, p < .001), and quality of life score increased by 17.5 (t[22] = 19.26, p < .001). For residents with sarcopenia in skilled nursing facilities, a 90-day strength training program with resistance and balance exercises may provide an option for decreasing the incidence of sarcopenia among that population

Keywords: muscle mass, muscle strength, older adults, PARIHS framework

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