Evaluation of microalbuminuria in patients with systemic sclerosis as an indicator of early renal damage and increased morbidity

AbstractIntroductionRenal involvement and systemic vascular damage have been shown to be significantly affecting prognosis in systemic sclerosis.Aim of workMicroalbuminuria detection in SSc patients as an indicator of early renal involvement and its correlation with various SSc clinical, laboratory parameters and severity of organ systems’ damage assessed by Scleroderma Assessment Questionnaire.Patients and methodsForty SSc patients (33 females and 7 males) with mean age of 27.48±12.56years and mean disease duration of 6.2±4.14years were included. Twenty-four (60%) had lSSc; 13 (32.5%) had dSSc and 3 (7.5%) patients had SSc sine scleroderma.ResultsEight (20%) had microalbuminuria and 9 (22.5%) patients had decreased creatinine clearance. Albumin/creatinine ratio was significantly higher among dSSc patients compared to those with lSSc and SSc sine scleroderma (X2=9.077; p=0.01). Albumin/creatinine ratio showed significant positive correlations with telangiectasia (r=0.322; p=0.04) and mRodnan’s skin score (r=0.352; p=0.026) and negative correlations with inter-incisor distance (r=−0.525; p=0.001) and pleurisy (r=−0.446; p=0.004). Albumin/creatinine ratio correlated significantly and positively with IMSS and IDS indices of SAQ (r=0.378, 0.32; p=0.016, 0.044, respectively). SSc patients with microalbuminuria showed significantly higher mean IDS than those without (1.058 vs. 0.631, p=0.04). No statistically significant correlations were found between creatinine clearance and the different demographic, clinical features and the indices of SAQ.ConclusionMicroalbuminuria compared to creatinine clearance may be a more sensitive indicator of early renal affection and predictor of increased morbidity

Cytotoxic Evaluation of Doxorubicin Combination with Baicalein and Resveratrol Against Hct116 and Hepg2 Cancer Cell Lines (Conference Paper) #

Combination of natural poly-phenolic compounds with chemotherapeutic agents is recently being a novel strategy in cancer therapy researches owing to their potential antioxidant and anti-inflammatory properties that modulate several intracellular signaling pathways. Resveratrol and Baicalein are well known poly-phenolic compounds that belong to stilbene and flavone subclasses, respectively. This study aims to investigate the possible enhancement effect of resveratrol and Baicalein when combined with doxorubicin using a different combination ratio and applied on two cancer cell lines: HCT116 (colorectal cancer cells) and HepG2 (hepatocellular cancer cells). It also investigates the possibility of such natural compounds to provide a protection effect on cardiocytes (H9C2) when resveratrol and Baicalein treatment followed by doxorubicin is used.  The two cancer cell lines were treated with different combination groups, including the combination between doxorubicin and Baicalein or resveratrol and the combination between the three compounds using a different combination ratio for both treatment groups (i.e., two drugs or three drugs combination). Treatment applied on cells, using cell density of 7000 cells /well and incubation time was 48 hrs. MTT test was performed to assay the cell viability. The results obtained showed that the cytotoxicity of doxorubicin in the two cancer cell lines has increased when combined with Baicalein and resveratrol. Doxorubicin IC50 decreased from 4.99 µg/ml to 0.3657 µg/ml and from 7.3 µg/ml to 0.676 µg/ml on HCT116 and HepG2 cells, respectively, using constant combination ratio (1:1:1). The combination of doxorubicin, Baicalein, and resveratrol has resulted in a less cardiotoxic effect compared to treatment with doxorubicin alone. This decrease was obviously seen when the three compounds were combined using a low concentration range and with a constant combination ratio. Conclusion: combinations of Baicalein and resveratrol with doxorubicin chemotherapeutic drug In Vitro had enhanced the cytotoxic activity of such a chemotherapeutic drug, while simultaneously eliminating its cardio-toxicity side effect.

Tumor-Associated Macrophage (TAM) and Angiogenesis in Human Colon Carcinoma

AIM: This study aimed to clarify how macrophages affect prognosis in cancer colon and their association with tumor angiogenesis.MATERIAL AND METHODS: Forty four biopsies of colon carcinoma and 15 of benign adenomatous polyps were investigated for macrophages infiltration and microvessels density using immunohistochemistry and image morphometric analysis. Macrophages and blood vessels were stained immunohistochemically by CD68 and F-VIII markers respectively. The morphometric analysis was carried out on the immunohistochemically stained slides using the Leica Qwin 500 Image Analyzer. Both of macrophages infiltration and microvessels density were correlated with histological tumor grade, stage and lymph node metastases and were correlated with each others.RESULTS: Macrophage infiltration was significantly higher in malignant cases than in benign polyps. High macrophage infiltration and hypervascularity were significantly correlated with T-staging and lymph nodes metastasis. A significant correlation was found between macrophage infiltration and microvessels densitie in malignant tumors where hypervascularity was significantly correlated with high macrophages infiltration.CONCLUSION: The significant correlation between macrophage infiltration and tumor angiogenesis suggests an interaction between macrophages and cancer cells stimulating microvessels formation, tumor invasion and metastasis in colon cancer. We recommend that macrophages infiltration should be evaluated to investigate their clinical value in development of individualized therapeutic regimens for management of colon carcinoma

Green Synthesis, Characterization, and Antibacterial Activity of Silver/Polystyrene Nanocomposite

A novel, nontoxic, simple, cost-effective and ecofriendly technique was used to synthesize green silver nanoparticles (AgNPs). The AgNPs were synthesized using orange peel extract as a reducing agent for silver nitrate salt (AgNO3). The particle size distribution of AgNPs was determined by Dynamic Light Scattering (DLS). The average size of silver nanoparticles was 98.43 nm. The stable dispersion of silver nanoparticles was added slowly to polystyrene solution in toluene maintaining the temperature at 70°C. The AgNPs/polystyrene (PS) nanocomposite solution was cast in a petri dish. The silver nanoparticles encapsulated within polymer chains were characterized by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) equipped with Energy Dispersive Spectroscopy (EDS) in addition to Transmission Electron Microscopy (TEM). The green AgNPs/PS nanocomposite film exhibited antimicrobial activity against Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae and Salmonella, and Gram-positive bacteria Staphylococcus aureus. Thus, the key findings of the work include the use of a safe and simple AgNPs/PS nanocomposite which had a marked antibacterial activity which has a potential application in food packaging

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

CYTOTOXIC ACTIVITY OF VARTHEMIA IPHIONOIDES ESSENTIAL OIL AGAINST VARIOUS HUMAN CANCER CELL LINES

Varthemia iphionoides is a perennial plant that belongs to Asteraceae family. This study investigates the cytotoxic effect of V. iphionoides essential oil on breast (MCF7), prostate (PC3), and chronic myelogenous leukemia (K562) and normal human fibroblast cell lines using MTT assay and flow cytometric analysis. In addition, GC-MS of the oil was carried out. The IC50 values for PC3, MCF7, K562 and fibroblast were 145.3, 188.8, 87.88 and 173.3 µg/ml, respectively. V. iphionoides essential oil was most effective against K562. Flow cytometric results for IC50 dose of V. iphionoides oil on K562 cells showed 32.2 % apoptosis in 24 h. GC-MS analysis resulted in the identification of 25 compounds. 1,8-Cineole, borneol, and α-cadinol were the major constituents of V. iphionoides volatile oil. In conclusion, this study reveals for the first time the cytotoxic activity of V. iphionoides essential oil on K562 cell line which may occur through apoptosis induction

ANTINOCICEPTIVE ACTION OF ONONIS SPINOSA LEAF EXTRACT IN MOUSE PAIN MODELS

Ononis spinosa (spiny restharrow) is a perennial herb that belongs to the Fabaceae family. Among several uses, the aerial parts of O. spinosa are used in traditional medicine for toothache. In this study, analgesic activity of the methanolic extract of leaves was studied. In writhing test, the 300 mg/kg and 600 mg/kg doses of O. spinosa extract produced 90.1% and 94.5% inhibition of abdominal cramps, respectively compared to 23.6% inhibition produced by 30 mg/kg diclofenac sodium. O. spinosa methanolic extract reduced the time of licking in early and late phases of formalin test. The inhibitory effect of O. spinosa extract was more pronounced in late phase. The lowest dose tested (300 mg/kg) of O. spinosa extract produced 81.0% inhibition compared to 50.5% inhibition in 30 mg/kg diclofenac sodium in the late phase of formalin test. This effect was not abrogated by glibenclamide, naloxone or atropine indicating that the action of O. spinosa in formalin test is not mediated by ATP-sensitive K+ channel, opioid or muscarinic receptors. In tail-flick and hot-plate tests, O. spinosa increased the latency time at 30 min and 150 min. Naloxone antagonized the action of O. spinosa in both tests suggesting an interaction with opioid receptor as a possible mechanism of O. spinosa in thermal pain models at the spinal and supraspinal levels. Phytochemical screening indicated the presence of phenolics, saponins, flavonoids, and terpenoids. Alkaloids, sterols, and anthraquinone glycosides were absent. HPLC analysis confirmed the presence kaempferol, apigenin and myricetin in the extract