Association of Red Cell Distribution Width and Mean Platelet Volume With Disease Activity in Rheumatoid Arthritis Patients.

BACKGROUND: The inner layer of the synovial joints is the primary target of rheumatoid arthritis, or RA, a chronic systemic inflammatory disorder that is linked to increasing disability, early mortality, and economic hardships. The objective is to determine the association of red cell distribution width (RDW) and mean platelet volume (MPV) with disease activity in RA. MATERIAL AND METHODS: A retrospective study was conducted between July 2021 and January 2022 in the outpatient rheumatology clinics at Gulab Devi Teaching Hospital. In this study, 100 consecutive participants with a diagnosis of RA fulfilling the ACR/EULAR 2010 classification criteria were enrolled. Patient's records were reviewed for age, gender, length of illness, smoking status, treatment history, current treatment regimen, concomitant medications, rheumatoid factor (RF), anti-cyclic citrulline peptide (anti-CCP) antibodies, and extra-articular manifestations. Laboratory investigations were reviewed for complete blood count including RDW and MPV, ESR, CRP, liver, and renal functions. Disease activity score DAS 28-ESR was used to quantify disease activity. To determine the relationship between different parameters and the RDW and MPV, linear regression research was conducted. RESULTS: According to the DAS28 score, 12% of patients were in remission, 9% had low, 34% had moderate, and 45% had high disease activity. DAS28 score was 5.01±1.72 (2.45-9.32) and RDW was 16.18±4.42. There was a strong positive correlation (r = 0.653) of RDW with the DAS28 score and it was statistically significant (p<0.001). MPV was 11.30±2.09 fL. There was a moderately positive correlation (r = 0.366) of MPV with the DAS28 score and it was statistically significant (p<0.001). CONCLUSION: Conclusively, both RDW and MPV are positively related to disease activity in patients with RA. These can be used as a simple tool for assessing disease activity and guiding the treatment.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

BACKGROUND: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. METHODS: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. RESULTS: The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. CONCLUSION: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

PURPOSE: The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. METHODS: We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. RESULTS: Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. CONCLUSION: Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells.

BACKGROUND: Recent studies suggest that numerous naturally occurring agents have the potential to kill cancer cells via mitochondrial dysfunction. Solanum nigrum is a herb widely used in alternative medical systems. This study aimed to investigate the cytotoxic effect of Solanum nigrum water extract (SNWE) against Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast Cancer-231 (MDA-MB-231) cells. METHODS: We used an MTT reduction assay for cytotoxicity analysis. To explore the mode of action, the cellular adenosine triphosphate (ATP) levels and mitochondrial membrane potential were analyzed using a colorimetric ATP assay and Rhodamine-123 fluorescent staining, respectively, during SNWE treatment for 72 h. RESULTS: The cytotoxic effect was significant in both cell lines, with IC50 values of 4.26 µg/mL and 5.30 µg/mL in MCF-7 and MDA-MB-231 cells, respectively. The 24, 48, and 72 h treatments of 100 µg/mL SNWE showed 0.85 ± 0.07, 0.38 ± 0.1, and 0.20 ± 0.1 nM ATP in MCF-7 cells and 0.94 ± 0.07, 0.84 ± 0.2 and 0.46 ± 0.2 nM in MDA-MB-231 cells, respectively. The SNWE treatment altered the mitochondrial membrane potential (ΔΨm) in a concentration-dependent manner in both the breast cancer cell lines, to 29.6 ± 4.1% in MCF-7 and 28.7 ± 4.17% in MDA-MB-231 cells, when compared with healthy mitochondria (100% ΔΨm). CONCLUSIONS: The cytotoxic effects of Solanum nigrum against breast cancer cells are associated with energy metabolism. Additional studies are warranted to test the anticancer effect of Solanum nigrum using an animal model of breast cancer.

Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome.

Objectives: Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-ß in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N = 488) and without Met-S (N = 1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results: A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-ß but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions: Serum levels of CRP, MPO, IL-6, and TNF-ß are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-ß levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention.

Laparoscopic sleeve gastrectomy for obesity treatment in adolescents and young adults: a systematic review and meta-analysis.

BACKGROUND: The incidence of obesity has been increasing in younger population, posing a significant impact on adolescents' life and health care system worldwide. METHODS: We critically analyzed the existing literature on the use of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity. We performed an in-depth evaluation of 37 studies and analyzed the effect of LSG in 2300 patients, aged ≤ 22 years. RESULTS: Mean body mass index (BMI) loss after LSG was 17.81 kg/m2. Gastroesophageal reflux was the most common complication. Most of the patients showed remission of comorbidities including hypertension, diabetes, and obstructive sleep apnea after LSG. CONCLUSIONS: These findings suggest that surgical intervention is highly beneficial for reducing BMI in appropriately selected adolescents and young adults suffering from obesity and comorbidities such as life-threatening obstructive sleep apnea.

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Evaluation of use of hyperbaric oxygen in suppression of hyper-proliferation in hypoxic NSCLC cells.

Hyperbaric oxygen therapy (HBO) is being researched as a potential adjuvant treatment for solid malignancies, such as NSCLC. It can reduce tumour hypoxia and has been found to slow tumour growth, stop dedifferentiation, and reduce apoptosis resistance in hypoxic NSCLC cells. Though HBO has shown promise in treating various cancers, more study is required to determine its precise mechanism of action in NSCLC. Analyze the effect of hyperbaric oxygen on the growth of hypoxic non-small cell lung cancer cells. We used the NSCLC cell lines A549 and H1299 to analyze aerobic glycolysis in vitro. Warburg effect testing included glucose absorption, lactate, adenosine triphosphate (ATP), and pyruvate measurements. Using a quantitative glycolytic flow model, we also analyzed the effect of HIF-1-induced genes on the flux of glucose metabolism. Lewis lung carcinoma (LLC) animal models in C57BL/6J mice were used to examine the development of lung tumours. The effects of pcDNA and HIF1A on glucose uptake, lactate production, pyruvate, and ATP levels were studied in A549 and H1299 NSCLC cells. While A549's glucose absorption increased over time, H1299's was dramatically decreased by HBO treatment. The pyruvate levels were more significant in H1299, particularly in hypoxia, and were lowered by HBO. In A549, the lactate content was more effective. After HBO treatment, glucose absorption was reduced while intracellular ATP levels were maintained. Overexpression of HIF-1a was able to counteract the effect of HBO on glycolytic gene expression. PFKP is a possible therapeutic target because HBO reduces the Warburg effect in NSCLC cells by downregulating HIF-1.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Role of Ondansetron in Reducing Methotrexate Intolerance in Patients with Inflammatory Arthritis.

OBJECTIVE: To determine the frequency of intolerance to Methotrexate (MTX) in patients with inflammatory arthritis by using MTX intolerance severity score, and evaluate the effects of Ondansetron in reducing MTX intolerance. STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Rheumatology clinic, Combined Military Hospital (CMH), Lahore, from 1st November 2021 to 30th April 2022. METHODOLOGY: Patients with inflammatory arthritis taking methotrexate regularly for >3 months participated in the study. The patients' age, gender, education level, marital status and smoking history were documented. The disease duration and disease activity was also recorded. Dose/duration/route/frequency and timing of MTX were noted. MTX intolerance was calculated with the use of the Methotrexate intolerance severity score (MISS) questionnaire. Those MTX intolerant patients who reported nausea and vomiting were prescribed ondansetron along with MTX and were followed up for the next 3 consecutive months. RESULTS: Out of 181 patients, 48(26.5%) showed methotrexate intolerance. The predominant symptom was nausea after taking MTX reported in 93.8% of the MTX intolerant patients followed by behavioural symptoms including restlessness and irritability reported among 79% and 77% of intolerant patients respectively. Those methotrexate intolerant patients who mainly had complaints of nausea and vomiting were started on ondansetron on the day of methotrexate and showed a significant reduction in the median of MISS score in the following two consecutive months (p <0.05) while at 3 months the median did not show further reduction as compared to second month (p=0.12). CONCLUSION: Ondansetron prescribed along with methotrexate in patients having complaints of nausea and vomiting with MTX, reduces the intolerance significantly. KEY WORDS: Rheumatoid arthritis, Methotrexate, Ondansetron, Nausea, Arthritis juvenile.

Phytochemical Profiling of Microalgae Euglena tuba and Its Anticancer Activity in Dalton's Lymphoma Cells.

INTRODUCTION: Natural phytochemicals are considered safe to use as therapeutic agents. There is a growing trend toward exploring anticancer effects of crude algal extracts or their active ingredients. Euglena tuba, a microalga, contains excellent antioxidant potential. However, the anticancer property of E. tuba has not been explored. This study investigates the chemical profiling as well as antitumor property of methanolic extract of E. tuba (ETME) against Dalton's lymphoma (DL) cells. MATERIALS AND METHODS: E. tuba, procured from northern part of India, was extracted in 70% methanol, dried at room temperature, and stored at -20 ∘C for future use. A freshly prepared aqueous solution of ETME of different concentrations was employed into each experiment. The ETME mediated anti-tumor response in Dalton's lymphoma was evaluated in the inbred populations of BALB/c (H2d) strain of mice of either sex at 8-12 weeks of age. The cytotoxicity of ETME in cancer cells, effects on morphology of cell and nucleus, alteration in the mitochondrial membrane potential, and level of expression of proapoptotic proteins (Bcl-2, cyt C, Bax and p53) were done using known procedures. RESULTS: The ETME contained high content of total alkaloids (96.02 ± 3.30 mg/100 mg), flavonoids (15.77 ± 2.38 mg/100 mg), carbohydrate (12.71 ± 0.59 mg/100 mg), ascorbic acid (12.48 ± 2.59 mg/100 mg), and phenolics (0.94 ± 0.05 mg/100 mg). Gas chromatography-mass spectrometry (GC-MS) analysis indicated the presence of 23 phytochemicals with known anticancer properties. DL cells treated with ETME exhibited significant and concentration dependent cytotoxicity. Florescent microscopy and flow cytometry of ETME treated DL cells indicated significant repair in cellular morphology and decreased mitochondrial potential, respectively. Western blot analysis displayed up-regulation of proapoptotic proteins (Bax, Cyt-c, p53) and down regulation of anti-apoptotic protein (Bcl2) in DL cells treated with ETME. CONCLUSIONS: The findings of this study clearly indicated that the anticancer property of ETME was mediated via reduction in mitochondrial potential and induction of apoptotic mechanism. Further studies are warranted to explore the anticancer activities of active ingredients present in this microalga of pharmaceutical importance.

Association between preventable risk factors and metabolic syndrome.

The risk factors associated with metabolic syndrome (Met-S) including hypertension, hyperglycemia, central obesity, and dyslipidemia are preventable, particularly at their early stage. There are limited data available on the association between Met-S and preventable risk factors in young adults. We randomly selected 2,010 Saudis aged 18-30 years, who applied to be recruited in military colleges. All the procedures followed the guidelines of International Diabetes Federation. The results showed that out of 2,010 subjects, 4088 were affected with Met-S. The commonest risk factors were high blood sugar (63.6%), high systolic and diastolic blood pressures (63.3 and 37.3%), and high body mass index (57.5%). The prevalence of prediabetes and diabetes were 55.2 and 8.4%, respectively. Obesity, diabetes, hypertension, and hypertriglyceridemia were significantly associated with Met-S. The frequency of smoking was significantly linked with the development of Met-S. The prevalence of Met-S was found to be significantly higher in individuals with sedentary lifestyle. In conclusion, the results of this study clearly indicate that military recruits, who represent healthy young adults, are also prone to Met-S. The findings of this study will help in designing preventive measures as well as public awareness programs for controlling the high prevalence of Met-S in young adults.

Cerebral venous sinus thrombosis as the initial presentation of essential thrombocythemia - A case report and literature review.

Myeloproliferative disorders (MPD) are associated with vascular thrombosis. Common sites for thrombosis are large arteries; however, less commonly, cerebral venous sinus thrombosis (CVST) has also been reported. It is rare to have CVST as an initial presentation of MPD. We discuss a male patient in whose presentation due to CVST led to the diagnosis of essential thrombocythemia (ET). Furthermore, we performed a literature review to evaluate the association of CVST with ET.

Profiles of Whole Blood Transfusion Recipients at a Teaching Hospital in Lahore, Pakistan.

Background Blood transfusion plays a vital role in medical practice. Evaluation of blood utilization in a blood bank is a crucial step in good transfusion practice. It is the inception towards assessing the present and future demands for blood and also avoiding unnecessary transfusions. Methods Retrospective analysis of one-year data, available in the blood bank of Gulab Devi Hospital Lahore, was done to study blood transfusion practice. Issue registers were accessed to retrieve the required information such as gender, age, blood group, pre-transfusion Hemoglobin level, ward, clinical diagnosis, and indication for the transfusion. The data was analyzed using SPSS version 20 software. Frequency and percentages were used to summarize categorical demographics and clinical variables. Results A total of 1181 units were requested from the hospital during our study period. Majority of the requests were for the female patients (69%) of the reproductive age group (21 to 30 years). Blood group B positive was most frequent in our study population. Maximum requests were from reproductive health departments (39.9%). Surgery was the major diagnostic category to require blood transfusions (31.8%). Elective surgery constituted the major indication requiring blood transfusion at our hospital (41.3%). Conclusion Blood utilization patterns vary significantly within geographical regions, hospital to hospital, and according to clinical practices as well as patients' clinical findings. Moreover, diseases burden, level of organization, and advancement of healthcare facilities in various settings contribute to the significant contrast in blood utilization trends.

Tuberculosis Screening via Chest X-Ray is Financially Burdensome in Previously Independently Living Elective Total Knee Arthroplasty Patients.

BACKGROUND: In 1995, to reduce the transmission of Tuberculosis (TB) the Centers for Disease Control and Prevention recommended that all patients discharged from hospitals be required to have chest x-rays (i.e., radiography) performed before admission to long term care facilities (LTCFs). Previously independently living patients (PILPs) who undergo elective total knee replacement (TKA) surgery are a population at higher risk to end up in LTCFs for rehabilitation. By 2017, the incidence of TB was 9,105 cases compared to 22,762 in 1995. However, the recommendations that hospitals be required to perform a chest x-ray in all patients (including PILPs) being transferred to LTCF's have remained in place. The purposes of this study were to: a) determine the incidence of TB-positive chest x-rays in PILPS discharged to LTCFs after undergoing elective TKA surgery, and b) assess the cost (i.e., both financial and possible exposure to unnecessary radiation) of mandated chest x-rays before hospital discharge to LTCF for PILPs. METHODS: Retrospective 2012-2017 patient chart data were collected from the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) to identify all elective TKAs for PILPs performed at two Ascension participating centers. Study data included sex, age, body mass index (BMI), length of stay, comorbidities, and chest x-ray results before discharge. Patients who underwent surgery for fracture, infection, trauma, or malignancy were excluded from the study. Categorical data were analyzed using Fisher's exact test and Student's t-test were used for continuous data. RESULTS: The authors identified 4,041 total elective TKA's, from which 500 PILPs were discharged to a LTCF due to functional, medical and/or social concerns. Chest x-rays were associated with 500 (100%) negative findings for TB. Overall hospital costs for chest x-rays for patient's being discharged to an extended care facility totaled $90,848. CONCLUSIONS: The mandated use of chest x-rays for TB screening of PILPs undergoing elective surgery TKA prior to discharge to LTCFs appear to place an unnecessary financial burden on the healthcare system. The mandatory use of x-rays for assessment of possible TB infection before transfer to LTCFs appears to also expose PILPs unnecessarily to radiation. Although further studies are needed to verify these results, the authors recommend that perhaps instead chest x-rays should be reserved for patients with specific comorbidities (e.g., patients on immunosuppressive therapy, with HIV, etc.) or for those patients residing in LTCFs prior to surgery.

Cellular antioxidant potential and inhibition of foodborne pathogens by a sesquiterpene ilimaquinone in cold storaged ground chicken and under temperature-abuse condition.

A sesquiterpene quinone, ilimaquinone, was accessed for its cellular antioxidant efficacy and possible antimicrobial mechanism of action against foodborne pathogens (Staphylococcus aureus and Escherichia coli) in vitro and in vivo. Ilimaquinone was found to be protective against H2O2-induced oxidative stress as validated by the reduction in the ROS levels, including increasing expression of SOD1 and SOD2 enzymes. Furthermore, ilimaquinone evoked MIC against S. aureus and E. coli within the range of 125-250 µg/mL. Ilimaquinone established its antimicrobial mode of action against both tested pathogens as evident by bacterial membrane depolarization, loss of nuclear genetic material, potassium ion, and release of extracellular ATP, as well as compromised membrane permeabilization and cellular component damage. Also, ilimaquinone showed no teratogenic effect against zebrafish, suggesting its nontoxic nature. Moreover, ilimaquinone significantly reduced the S. aureus count without affecting the sensory properties and color values of cold-storaged ground chicken meat even under temperature abuse condition.

Recent Trends of Metabolic Syndrome and Its Components in Military Recruits from Saudi Arabia.

Metabolic syndrome (Met-S) constitutes the risk factors and abnormalities that markedly increase the probability of developing diabetes and coronary heart disease. An early detection of Met-S, its components and risk factors can be of great help in preventing or controlling its adverse consequences. The aim of the study was to determine the prevalence of cardio-metabolic risk factors in young army recruits from Saudi Arabia. A total of 2010 Saudis aged 18-30 years were randomly selected from groups who had applied to military colleges. In addition to designed questionnaire, anthropometric measurements and blood samples were collected to measure Met-S components according to the International Diabetes Federation (IDF) criteria. Met-S prevalence was 24.3% and it was higher in older subjects than the younger ones. There were significant associations between Met-S and age, education level and marital status. The most common Met-S components were high fasting blood sugar (63.6%) followed by high blood pressure (systolic and diastolic, 63.3% and 37.3% respectively) and high body mass index (57.5%). The prevalence of pre-diabetes and diabetes were found to be 55.2% and 8.4%, respectively. Hypertriglyceridemia was found in 19.3% and low levels of high-density lipoproteins (HDL) in 11.7% of subjects. In conclusion, there is a high prevalence of Met-S in young adults of Saudi Arabia. There is a need for regular monitoring of Met-S in young populations to keep them healthy and fit for nation building. It is also important to design and launch community-based programs for educating people about the importance of physical activity, cessation of smoking and eating healthy diet in prevention of chronic diseases.

Pro-Apoptotic and Immunotherapeutic Effects of Carbon Nanotubes Functionalized with Recombinant Human Surfactant Protein D on Leukemic Cells.

Nanoparticles are efficient drug delivery vehicles for targeting specific organs as well as systemic therapy for a range of diseases, including cancer. However, their interaction with the immune system offers an intriguing challenge. Due to the unique physico-chemical properties, carbon nanotubes (CNTs) are considered as nanocarriers of considerable interest in cancer diagnosis and therapy. CNTs, as a promising nanomaterial, are capable of both detecting as well as delivering drugs or small therapeutic molecules to tumour cells. In this study, we coupled a recombinant fragment of human surfactant protein D (rfhSP-D) with carboxymethyl-cellulose (CMC) CNTs (CMC-CNT, 10-20 nm diameter) for augmenting their apoptotic and immunotherapeutic properties using two leukemic cell lines. The cell viability of AML14.3D10 or K562 cancer cell lines was reduced when cultured with CMC-mwCNT-coupled-rfhSP-D (CNT + rfhSP-D) at 24 h. Increased levels of caspase 3, 7 and cleaved caspase 9 in CNT + rfhSP-D treated AML14.3D10 and K562 cells suggested an involvement of an intrinsic pathway of apoptosis. CNT + rfhSP-D treated leukemic cells also showed higher mRNA expression of p53 and cell cycle inhibitors (p21 and p27). This suggested a likely reduction in cdc2-cyclin B1, causing G2/M cell cycle arrest and p53-dependent apoptosis in AML14.3D10 cells, while p53-independent mechanisms appeared to be in operation in K562 cells. We suggest that CNT + rfhSP-D has therapeutic potential in targeting leukemic cells, irrespective of their p53 status, and thus, it is worth setting up pre-clinical trials in animal models.

Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways.

P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1-gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR.