Utilisation of the health belief model to study the behavioural intentions relating to obesity management among university students: a cross-sectional study.

BACKGROUND: Overweight and obesity are excessive fat accumulations linked with many health problems, including heart diseases, type 2 diabetes and cancer. Multiple studies have demonstrated that beliefs about overweight, obesity and self-efficacy play essential roles in the success of interventions for obesity management. OBJECTIVES: This study aimed to identify the perceptions of university students of overweight and obesity using the health belief model (HBM) and to analyse their association with the body mass index (BMI) categories of the students. DESIGN: A cross-sectional questionnaire-based study and a multistage sampling technique were used to ensure the recruitment of students from selected colleges of Jazan University-Saudi Arabia. SETTING: Six colleges of Jazan University were randomly selected to ensure equal representation of health sciences, sciences and humanities colleges. PARTICIPANTS: A total of 579 students completed an online survey between January and April 2023. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were demographic characteristics and HBM constructs. Secondary outcome measures were behavioural intentions relating to obesity management. RESULTS: This study demonstrated that gender and self-reported family history of obesity were significantly correlated with the BMI categories of the students (p <0.001). Students in the underweight category showed the highest mean score for perceived severity (3.62 ±0.08). Perceived self-efficacy in exercise and diet was significantly associated with BMI categories, with adjusted ORs of 2.82 (2.10 to 3.79) and 1.51 (1.09 to 2.09), respectively. Perceived barriers to healthy eating and regular physical activity were significantly related to the behavioural intentions of obesity management. Multivariate logistic regression showed that perceived severity, perceived cues to action, perceived barriers and self-efficacy in dieting and exercise were significant predictors of behavioural intentions for the management of obesity. CONCLUSION: This study underscores the need for tailored health promotion strategies that consider the perceptions and beliefs of people about the management of obesity.

Knowledge, attitude, and perception of robotic-assisted surgery among the general population in Saudi Arabia: a cross-sectional study.

Minimally invasive surgery (MIS) has revolutionized surgical practices, with robotic-assisted surgery (RAS) significantly advancing. However, the understanding and acceptance of RAS vary, impacting its widespread adoption. This study aims to assess Saudi Arabians' attitudes and comprehension of RAS, which is crucial for promoting its integration into surgical procedures. A cross-sectional study was conducted in various Saudi Arabian cities. A total of 1449 participants were included, while participants with cognitive issues were excluded. Demographic information, knowledge, technology experience, attitudes, and perceptions about RAS were collected using an online self-administered questionnaire. Data were analyzed using descriptive and inferential statistics. Of the participants, 51.1% demonstrated awareness of RAS, mainly through social media (36.9%). Factors influencing awareness included gender, education, income, occupation, computer literacy, and technology comfort. Gender disparities were evident in attitudes and perceptions toward RAS. Concerns about RAS included robot malfunction (62.0%), surgical errors (45.4%), and surgeon competency (44.7%). 36.4% of the participants believe RAS is faster, 29.9% believe RAS is less painful, and 25.3% believe RAS has fewer complications. Positive perceptions encompassed the belief that robot-using surgeons are more skilled (44.5%) and hospitals offering RAS are better (54.3%). Notably, 47.7% expressed willingness to consider RAS as a treatment option. The study underscores the significance of promoting awareness and informed decisions to ensure the successful integration of RAS in surgical practices. Addressing concerns and misconceptions and enhancing public comprehension are pivotal for facilitating informed decision-making and fostering RAS acceptance within Saudi Arabia's surgical landscape.

Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease.

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE.

BACKGROUND: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC. PATIENTS AND METHODS: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively. RESULTS: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D. CONCLUSIONS: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2. TRIAL REGISTRATION: NCT03812796 (registered 23rd January 2019).

Association Between Subclinical Hypothyroidism and the Prognosis of Diabetes Mellitus and Subsequent Complications: A Retrospective Cohort Study.

Background Diabetes mellitus (DM) and subclinical hypothyroidism (SCH) are prevalent metabolic and endocrine disorders. Previous studies have suggested potential associations between SCH and metabolic disorders, including DM. This study aimed to explore the relationship between SCH and DM in patients from the Qassim Region in Saudi Arabia. Methods A retrospective cohort study was conducted on patients who attended the Qassim University clinics from December 2017 to December 2021. Participants were divided into two groups: SCH patients without a history of DM and age- and sex-matched controls without SCH or DM. Parameters, such as DM occurrence, DM duration, glycosylated hemoglobin (HbA1c) values, and metformin use, were evaluated. Results The prevalence of DM was 70.4% in the SCH group and 83.3% in the non-SCH group, with no significant difference between the groups (p=0.203). The mean HbA1c values and DM duration showed no significant variations between the two groups. However, metformin use was significantly higher in the SCH group at 74.1% compared to 50.0% in the non-SCH group (p=0.047). No correlation was observed between HbA1c and thyroid-stimulating hormone (TSH) levels. Conclusions While the study indicates a potential association between SCH and DM management, especially with regard to metformin usage, there does not appear to be a significant relationship between SCH and DM development or progression in this population.

Reported Symptoms and Associated Factors of Carpal Tunnel Syndrome in Qassim Region: A Cross-Sectional Study.

Background Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, occurring through compression of the median nerve as it passes under the transverse carpal ligament. Symptoms include nocturnal pain and paresthesias confined to the thumb, middle, and index fingers. Objective The purpose of this study is to determine the prevalence of CTS symptoms and the associated risk factors in Qassim Province, Kingdom of Saudi Arabia. Materials and methods A total of 314 participants were recruited from Qassim Province using an online survey, which included demographic questions and the Boston Carpal Tunnel Questionnaire (BCTQ). The association between categorical variables was assessed using the Chi-square test or Fisher's exact test, as appropriate. Additionally, an independent t-test was performed to compare quantitative variables. A p-value of less than 0.05 was considered statistically significant. Result The prevalence of CTS in the Qassim population was found to be 19.7%. The most significant risk factors for CTS were age, chronic illnesses, and employment status (p < 0.001). The most frequently reported symptoms included daytime pain and weakness (82.3%), while obesity emerged as the most prevalent chronic disease (21%). The mean symptom severity score (SSS) was significantly higher for individuals who were awoken from pain (t = -5.89; p < 0.001) and for those who experienced awakening due to numbness and tingling (t = -5.59; p < 0.001). Conclusion According to our sampled cohort, 19.7% of individuals had symptoms of CTS etiology. Multiple risk factors for CTS were identified. Notably, the development of CTS symptoms was significantly associated with individuals aged 50 and older, employment status, and the presence of related chronic diseases.

The Prevalence and Impact of Allergic Rhinitis on Asthma Exacerbations in Asthmatic Adult Patients in the Qassim Region of Saudi Arabia: A Cross-Sectional Study.

Objective We aim to evaluate the prevalence and impact of allergic rhinitis comorbidity in asthmatic patients in the Qassim region and identify whether rhinitis affects asthma control. Methods This is an observational cross-sectional study on asthmatic adults who live in the Qassim region of Saudi Arabia. An online questionnaire was distributed through social media. The questionnaire is composed of the validated Arabic versions of the Score for Allergic Rhinitis (SFAR) questionnaire, the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines, and the Asthma Control Test (ACT) questionnaire. Results The total number of participants was 380; however, after 98 were excluded, 282 asthmatic patients were included in this study. Of them, 33% had allergic rhinitis. Females constitute 67% of the study participants, while males comprise 33%. The findings of the study indicate that there is a significant association between allergic rhinitis and asthma control in the Qassim region. Symptoms such as runny nose, sneezing, and nasal obstruction are significantly associated with poor asthma control (p = 0.006). Having a known family history of asthma, eczema, or allergic rhinitis is significantly associated with worse asthma control (0.004). Conclusion In summary, this study found a high prevalence of rhinitis symptoms comorbidity in asthmatic patients in the Qassim region. Overall, the study established the existence of a relationship between allergic rhinitis and asthmatic control. Symptoms such as a runny nose, sneezing, and nasal obstruction are significantly associated with allergic rhinitis and asthmatic symptoms. However, there is no significant association between nose problems that occur in specific seasons or months and allergic rhinitis and asthmatic symptoms, suggesting that seasonality may not have a strong impact on asthma control. House dust mite allergies have a borderline significant association with allergic rhinitis and asthmatic symptoms. Having a family history of asthma, eczema, or allergic rhinitis is associated with allergic rhinitis and asthmatic symptoms, thereby indicating a significant impact on asthma control.

A one-health approach to design an mRNA-based vaccine candidate against the lumpy skin disease virus as an alternative to live-attenuated vaccines.

OBJECTIVE: Recently, lumpy skin disease (LSD) has been spread over the Asian, European, and Middle Eastern regions making it a significant hazard to the chain of cattle production, milk production, and human milk consumption, requiring prompt attention. Lumpy skin disease virus has high morbidity and low fatality rates, but its infections have led to terrible economic and agricultural consequences. Although live-attenuated vaccines have been commercialized, farmers in different regions have not taken them well because of the allergic responses against the vaccines. The study aims to develop an mRNA-based vaccine candidate for LSDV, using immunoinformatic approaches to minimize allergenicity and homology while maximizing immunogenic potential. MATERIALS AND METHODS: The study used extensive immunoinformatic approaches to shortlist five proteins from the LSDV genome that belong to the transmembrane region and are crucial in early viral interaction with host cells. The B-cell and T-cell-specific epitopes were chosen based on non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. The construct's stability, hydrophilicity, and antigenic potential were analyzed using the instability index, Grand Average of Hydropathicity (GRAVY) index, and antigenicity, respectively. RESULTS: We selected a total of 34 epitopes, consisting of 12 B-cell-specific epitopes and 22 T-cell-specific epitopes. These epitopes were chosen based on their characteristics such as non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. Specifically, 11 epitopes were selected for Major Histocompatibility Complex-I, and another 11 epitopes were chosen for Major Histocompatibility Complex-II. The inclusion of the RS09 adjuvant enhanced the immunogenic potential of the vaccine. The instability index was found to be 38.60. Additionally, the GRAVY index, indicating hydrophilicity, was calculated as -0.151. Furthermore, the antigenicity value of 0.6073 confirmed its potential to elicit an immune response. Further supporting its immunogenic potential, strong immune stimulation was observed, with IgM+IgG titers reaching 6,000 (arbitrary units) and IFNg titers measuring 400,000 ng/mL. These results provide additional evidence of the vaccine's ability to stimulate a robust immune response. CONCLUSIONS: The study results indicate that the developed mRNA-based vaccine candidate for LSDV has high immunogenic potential and could serve as an effective alternative to live-attenuated vaccines. Further experimental validations are required to test its efficacy. The study also highlights the potential of the One-Health approach to tackle non-zoonotic diseases that have significant consequences for the environment and humanity.

Media use, dietary intake, and diet quality of adolescents in Saudi Arabia.

BACKGROUND: Excessive media use can affect diet of adolescents, but relevant data in Saudi Arabia are lacking. The present study aimed to explore the association between media use, dietary intake, and diet quality among adolescents. METHODS: This cross-sectional study included data of 631 adolescents (ages 11-18 years) who were randomly recruited from 16 schools located in two main cities in the Western region of Saudi Arabia (Madinah and Jeddah). Envelopes including a questionnaire were sent home to collect sociodemographic data. Students then completed the short-form food frequency questionnaire to assess diet quality. Data on media use, anthropometrics, and 24-h dietary recalls were also collected. RESULTS: A high proportion of adolescents (86.2%) exceeded media use recommendations of ≤2 h per day. Significantly higher proportions of younger adolescents, males, and non-Saudis reported media use within the recommendation compared to their peers. Media use predicted lower diet quality score (B = -0.67 [95% CI: -1.09 to -0.28]) and lower intake of calcium, zinc, vitamin D, and vitamin C (B = -104 [95% CI: -203 to -5.24], B = -2.13 [95% CI: -4.15 to -0.11], B = -23.5 [95% CI: -41.3 to -5.65], B = -24.0 [95% CI: -45.1 to -2.96], respectively). CONCLUSION: Interventions to limit media use are urgently needed for adolescents in Saudi Arabia to improve diet quality and overall nutritional health. IMPACT: Excessive media use can affect diet of adolescents, but relevant data are lacking in Saudi Arabia. The majority of adolescents exceed the recommendations for media use. Media use was negatively associated with diet quality and intake of calcium, zinc, vitamin D, and vitamin C. This study will inform public health entities and policy makers to draw evidence-based, culturally tailored recommendations and develop nutrition interventions to enhance diet quality and nutritional status of adolescents. Findings of this study highlight the urgency to develop intervention programs and policies that aim to limit media use among adolescents.

Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.

BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer. METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder. RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047). CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.

Serum interleukin-33 (IL-33) in children with active systemic lupus erythematosus: A cross-sectional study.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is associated with the development of different autoimmune diseases as systemic lupus erythematosus (SLE). So, the purpose of this cross-sectional study was to measure the serum IL-33 in children with SLE (c-SLE) in relation to their SLE disease activity index. This study was conducted upon 50 c-SLE patients in comparison to 50 normal matched children as a control group. Disease activity was assessed according to SLE Disease Activity Index (SLEDAI-2K). Serum IL-33 was measured by an Enzyme-linked immunosorbent assay (ELISA). Serum IL-33 was significantly higher in c-SLE patients (median: 157.47, IQR:64.49-237.57ng/l) than controls (median: 10.9, IQR: 10.04-12.51ng/L) (P= 0.001) and negatively correlated with serum C3 and C4 levels. Serum IL-33 levels were significantly higher in high disease activity status (HDAS) patients (SLEDAI-2K ≥ 10) (298.47 ± 78.84ng/l) than lupus low disease activity status (LLDAS) patients (SLEDAI-2K < 10) (112.18 ± 16.23ng/l) (P= 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff of serum IL-33 level to predict the disease activity was ≥141.3 ng/l with a sensitivity of 93%, a specificity of 90% and accuracy 97%. We concluded that serum IL-33 was higher in c-SLE patients and positively related to the disease activity index so could be used as a disease activity marker.

Biosynthesis of copper oxide nanoparticles mediated Annona muricata as cytotoxic and apoptosis inducer factor in breast cancer cell lines.

This study investigated for the first time a simple bio-synthesis approach for the synthesis of copper oxide nanoparticles (CuO NPs) using Annona muricata L (A. muricata) plant extract to test their anti-cancer effects. The presence of CuONPs was confirmed by UV-visible spectroscopy, Scanning electron microscope (SEM), and Transmission electron microscope (TEM). The antiproliferative properties of the synthesized nanoparticles were evaluated against (AMJ-13), (MCF-7) breast cancer cell lines, and the human breast epithelial cell line (HBL-100) as healthy cells. This study indicates that CuONPs reduced cell proliferation for AMJ-13 and MCF-7. HBL-100 cells were not significantly inhibited for several concentration levels or test periods. The outcomes suggest that the prepared copper oxide nanoparticles acted against the growth of specific cell lines observed in breast cancer. It was observed that cancer cells had minor colony creation after 24 h sustained CuONPs exposure using (IC50) concentration for AMJ-13 was (17.04 µg mL-1). While for MCF-7 cells was (18.92 µg mL-1). It indicates the uptake of CuONPs by cancer cells, triggering apoptosis. Moreover, treatment with CuONPs enhanced Lactate dehydrogenase (LDH) production, probably caused by cell membrane damage, creating leaks comprising cellular substances like lactate dehydrogenase. Hence, research results suggested that the synthesized CuONPs precipitated anti-proliferative effects by triggering cell death through apoptosis.

Rare Heterogeneous Adverse Events Associated with mRNA-Based COVID-19 Vaccines: A Systematic Review.

Background: Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. Methods: A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Results: Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. Conclusions: As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.

A pediatric case of TEK-Related malformations and marfanoid habitus: an incidental finding or a feature?

Vascular malformations encompass a wide range of complex vascular lesions. Due to the extreme variability of clinical presentation, classification and their related syndromes presents a challenge. Here we describe a case of a boy presenting with Marfanoid habitus, cutaneous vascular malformations, and severe acute anemia due to ileal venous malformations. Although a panel of genetic markers for the Marfan phenotype was negative, we identified a de novo mutation in the TEK gene in the patient. This case supports expansion of the phenotypic spectrum of TEK-related vascular malformations.

Hypospadias and the Use of the Ages and Stages Questionnaire to Evaluate Neurodevelopmental Status of Boys with Hypospadias.

INTRODUCTION: Placental insufficiency is one of the reasons for the reduction of hormone production. Thus, if one of the suspected causes of hypospadias is placental insufficiency, then the neurodevelopmental status of boys with hypospadias may be impaired. The aim of this study was to evaluate the neurodevelopmental status of boys with hypospadias and guide the parents of those who need support to related departments for early intervention. MATERIALS AND METHODS: Boys were divided into two groups, those with hypospadias (group H) and healthy children undergoing traditional circumcision (group C). The parents of the boys completed the Ages and Stages Questionnaire (ASQ) and ASQ-Social Emotional (SE), both of which are screening instruments for the early identification of developmental and social-emotional problems, respectively. RESULTS: Seventy-eight boys had hypospadias and 59 were admitted for traditional circumcision. The group H had statistically significant more impaired scores than group C in communication, gross motor, and personal-social skill sections. The multivariate logistic regression analysis revealed that hypospadias was the independent predictive factor for communication and personal-social skills. CONCLUSION: Hypospadias and neurologic impairment may share common etiologic factors. Accordingly, physicians should keep in mind that if a boy presents with hypospadias, the possibility of having neurologic impairment is higher than normal population and early intervention has crucial importance. Every boy with hypospadias should be evaluated for neurodevelopmental status.

Design, analysis, and experimental investigation of micro-displacement amplification compliant mechanism for micro-transducers.

This paper presents experimental force and buckling analysis of a compliant micro-displacement amplification mechanism fabricated using the commercially available PolyMUMPs process. The proposed mechanism proficiently amplifies displacement, at two output ends, with an optimal amplification factor of 7.2. Buckling analysis revealed that an amplification factor ranging from 2.8 to 11 may be achieved for an input displacement varying from 0.1 to 7.5 µm. Based on the analysis, the optimal value of the amplification factor is found to be 7.2 with an input displacement of 3.5 µm at the operational force of 60 µN having a buckling load factor (BLF) >1. Critical load magnitude is 187 µN having BLF = 1. Buckling occurred when loading exceeded the critical load value, having BLF <1, and the mechanism failed to produce a significant amplification factor. Static analysis showed that stresses produced are within the safe region, and the structural integrity of the mechanism is not compromised having a factor of safety of 1.4. Modal analysis predicted that the natural frequency of the desired mode is 35.47 kHz. Dynamic simulations, under 15 g dynamic load with a frequency range of 30-40 kHz, confirm the possibility of integrating the proposed mechanism with MEMS devices. Parametric optimization comprehends that length and angle are the two major geometric parameters that govern the working range, force, and amplification factor. For input displacements below 1 µm, the amplification factor is even higher, which is highly beneficial for amplifying small displacements. Static, modal, and dynamic analyses of the designed mechanism have been carried out using finite element method based commercial software IntelliSuite®. The experimental results showed that this mechanism can provide the same amplified displacement at two output points and is self-sufficient to be incorporated as an intermediate compliant mechanism for enhancing the output in the case of both static and dynamic micro-devices.

LC-MS/MS Proteomic Study of MCF-7 Cell Treated with Dox and Dox-Loaded Calcium Carbonate Nanoparticles Revealed Changes in Proteins Related to Glycolysis, Actin Signalling, and Energy Metabolism.

One of the most prevalent death causes among women worldwide is breast cancer. This study aimed to characterise and differentiate the proteomics profiles of breast cancer cell lines treated with Doxorubicin (DOX) and Doxorubicin-CaCO3-nanoparticles (DOX-Ar-CC-NPs). This study determines the therapeutic potential of doxorubicin-loaded aragonite CaCO3 nanoparticles using a Liquid Chromatography/Mass Spectrometry analysis. In total, 334 proteins were expressed in DOX-Ar-CC-NPs treated cells, while DOX treatment expressed only 54 proteins. Out of the 334 proteins expressed in DOX-CC-NPs treated cells, only 36 proteins showed changes in abundance, while in DOX treated cells, only 7 out of 54 proteins were differentially expressed. Most of the 30 identified proteins that are differentially expressed in DOX-CC-NPs treated cells are key enzymes that have an important role in the metabolism of carbohydrates as well as energy, including: pyruvate kinase, ATP synthase, enolase, glyceraldehyde-3-phosphate dehydrogenase, mitochondrial ADP/ATP carrier, and trypsin. Other identified proteins are structural proteins which included; Keratin, α- and ß-tubulin, actin, and actinin. Additionally, one of the heat shock proteins was identified, which is Hsp90; other proteins include Annexins and Human epididymis protein 4. While the proteins identified in DOX-treated cells were tubulin alpha-1B chain and a beta chain, actin cytoplasmic 1, annexin A2, IF rod domain-containing protein, and 78 kDa glucose-regulated protein. Bioinformatics analysis revealed the predicted canonical pathways linking the signalling of the actin cytoskeleton, ILK, VEGF, BAG2, integrin and paxillin, as well as glycolysis. This research indicates that proteomic analysis is an effective technique for proteins expression associated with chemotherapy drugs on cancer tumours; this method provides the opportunity to identify treatment targets for MCF-7 cancer cells, and a liquid chromatography-mass spectrometry (LC-MS/MS) system allowed the detection of a larger number of proteins than 2-DE gel analysis, as well as proteins with maximum pIs and high molecular weight.

Design and analysis of four-jaws microgripper with integrated thermal actuator and force sensor for biomedical applications.

This research paper presents design and analysis of the multi-jaw microgripper that can manipulate microbiological organisms and species, cell probing and measurement, biomedical sample sorting, and preparation. Four jaws, actuated with a single thermal chevron actuator, can grip microbiological species ranging from 300 to 700 µm, 1 to 340 µm, 100 µm pool, and 1 to 120 µm spongy cells, respectively. Jaws are designed in such a way that they can grip regular, irregular, and spongy shaped biological species and their organelles. Parametric analysis of the microgripper exhibited that at 10 V, the efficiency of the thermal actuator is at maximum with respect to displacement, force, and temperature. To enhance displacement to voltage ratio and increase the energy efficiency, a class 3 lever mechanism has been incorporated. The amplification factors at four jaws are 17.21, 13.82, 4.02, and 4.93, respectively. For controlled application of the force to microspecies, two electrostatic force sensors have been amalgamated with jaws having capacitive sensitivities of 1.59 nf/µm, 1.91 nf/µm, 17 nf/µm, and 14.5 nf/µm, respectively. Electrothermal, static, and electrostatic analyses have been carried out with the finite element methods based software IntelliSuite®. Stress magnitudes are within the limits of structural integrity of silicon having a factor of safety 2.5. Thermal analysis revealed that at a differential voltage of 10 V, the maximum temperature goes up to 425 °C. Buckling analysis results depicted that the critical load for the thermal actuator is 241 µN with the buckling load factor greater than unity. This paper focuses on microbiological applications only; however, the designed microgripper can be used to manipulate micro-objects, microstructures, microelectronics parts, and micro assembly.

Protein profile of MCF-7 breast cancer cell line treated with lectin delivered by CaCO3NPs revealed changes in molecular chaperones, cytoskeleton, and membrane-associated proteins.

The second most predominant cancer in the world and the first among women is breast cancer. We aimed to study the protein abundance profiles induced by lectin purified from the Agaricus bisporus mushroom (ABL) and conjugated with CaCO3NPs in the MCF-7 breast cancer cell line. Two-dimensional electrophoresis (2-DE) and orbitrap mass spectrometry techniques were used to reveal the protein abundance pattern induced by lectin. Flow cytometric analysis showed the accumulation of ABL-CaCO3NPs treated cells in the G1 phase than the positive control. Thirteen proteins were found different in their abundance in breast cancer cells after 24 h exposure to lectin conjugated with CaCO3NPs. Most of the identified proteins were showing a low abundance in ABL-CaCO3NPs treated cells in comparison to the positive and negative controls, including V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP. Hornerin, tropomyosin alpha-1 chain, annexin A2, and protein disulfide-isomerase were up-regulated in comparison to the positive. Bioinformatic analyses revealed the regulation changes of these proteins mainly affected the pathways of 'Bcl-2-associated athanogene 2 signalling pathway', 'Unfolded protein response', 'Caveolar-mediated endocytosis signalling', 'Clathrin-mediated endocytosis signalling', 'Calcium signalling' and 'Sucrose degradation V', which are associated with breast cancer. We concluded that lectin altered the abundance in molecular chaperones/heat shock proteins, cytoskeletal, and metabolic proteins. Additionally, lectin induced a low abundance of MCF-7 cancer cell proteins in comparison to the positive and negative controls, including; V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP.

Immunohistochemical expression of substance P in breast cancer and its association with prognostic parameters and Ki-67 index.

BACKGROUND: The neuropeptide substance P is a potential biomarker and therapeutic target in cancer. The main objectives of this study were to investigate the expression level of substance P in different breast cancer molecular subtypes and identify its association with clinicopathological parameters of patients and with Ki-67 index. METHODS: A retrospective analysis was performed for a total of 164 paraffin-embedded breast cancer tissue samples [42 Her2/neu-enriched, 40 luminal A, 42 luminal B (triple-positive) and 40 triple negative subtypes]. The tissue microarray slides containing specimens were used to determine the expression of substance p and Ki-67 by immunohistochemical staining. RESULTS: The mean age of the cohort was 51.35 years. Twenty two percent of cases had low substance P expression levels (TS ≤ 5), while 78% had high expression levels (TS > 5). A significant association was found between SP expression level and breast cancer molecular subtype (p = 0.002), TNM stage (p = 0.034), pN stage (p = 0.013), axillary lymph node metastasis (p = 0.004), ER and PR statuses (p<0.001) and history of DCIS (p = 0.009). The average percentage of Ki-67 expression was 27.05%. When analyzed as a continuous variable, significant differences were observed between the mean Ki-67 scores and molecular subtype (p = 0.001), grade (p = 0.003), pN stage (p = 0.007), axillary lymph node metastasis (p = 0.001), and ER and PR statuses (p <0.001). CONCLUSION: SP is overexpressed in most of the analyzed tissues and has a negative prognostic value in the breast cancer patients. Besides substance P is a potential therapeutic target in breast cancer.