Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.

The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats.

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-ß1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-ß1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.

Anti-inflammatory and antioxidant efficacy of lavender oil in experimentally induced thrombosis.

BACKGROUND: Lavender oil (LO) possesses anti-inflammatory, antioxidant, antifungal, antibacterial, sedative, cardio-protective, and antinociceptive properties. Thrombosis and inflammation are interplayed processes that interact and influence one another. Our research compared three routes of administration to assess the efficacy of pretreatment with LO on carrageenan-induced thrombosis in rat tail. MATERIALS AND METHODS: Wistar-Bratislava white rats were randomly divided into five groups of ten rats each and pretreated 3 consecutive days prior the inducement of thrombosis to with one dose of LO (150 mg/kg body weight (b.w.)): per os by gavage (TLOPO group), intraperitoneal (TIPLO group) and subcutaneous (TSCLO group). We also have a control (C, received saline solution 0.9% and DMSO (vehicle) 1 ml intraperitoneal (i.p.)) group and a group with thrombosis (T group, received saline solution 0.9% plus vehicle 1 ml i.p.). Histopathological examinations were conducted together with measurements of the circulating levels of three oxidative stress markers, antioxidant effect (TAC and THIOL), and three proinflammatory cytokines (TNF- α, RANTES, and MCP-1). RESULTS: When administered intraperitoneally, lavender oil has the best efficacy on circulating levels of oxidative stress parameters (MDA, NOx, TOS), one oxidative stress marker (THIOL), and all studied proinflammatory cytokines (p-values < 0.02). Moreover, TIPLO displayed the closest values for bleeding and clotting time to the C group, as well as the lowest length of the thrombus than the T, TPOLO, and TSCLO groups (p-values < 0.001). The TIPLO group has histological appearance comparable to the C group, with the exception of the presence of oedema. CONCLUSIONS: Lavender oil pretreatment with intraperitoneal administration as three days, one-dose per day, showed anti-inflammatory and antioxidant efficacy in experimentally induced thrombosis.

The Influence of the Learning Curve on Clinical Outcomes in Balloon-Expandable versus Self-Expandable Transfemoral Transcatheter Aortic Valve Implantation.

INTRODUCTION: Balloon-expandable (BE) and self-expandable (SE) prostheses are the main types of devices currently used in transcatheter aortic valve implantation (TAVI). Despite the different designs, clinical practice guidelines do not make any specific recommendation on the selection of one device over the other. Most operators are trained in using both BE and SE prostheses, but operator experience with each of the two designs might influence patient outcomes. The aim of this study was to compare the immediate and mid-term clinical outcomes during the learning curve in BE versus SE TAVI. METHODS: The transfemoral TAVI procedures performed in a single center between July 2017 and March 2021 were grouped according to the type of implanted prosthesis. The procedures in each group were ordered according to the case sequence number. For each patient, a minimum follow-up time of 12 months was required for inclusion in the analysis. The outcomes of the BE TAVI procedures were compared with the outcomes of the SE TAVI procedures. Clinical endpoints were defined according to the Valve Academic Research Consortium 3 (VARC-3). RESULTS: The median follow-up time was 28 months. Each device group included 128 patients. In the BE group, case sequence number predicted mid-term all-cause mortality at an optimal cutoff value ≤58 procedures (AUC 0.730; 95% CI: 0.644-0.805; p < 0.001), while in the SE group, the cutoff value was ≤85 procedures (AUC 0.625; 95% CI: 0.535-0.710; p = 0.04). A direct comparison of the AUC showed that case sequence number was equally adequate in predicting mid-term mortality, irrespective of prosthesis type (p = 0.11). A low case sequence number was associated with an increased rate of VARC-3 major cardiac and vascular complications (OR 0.98 95% CI: 0.96-0.99; p = 0.03) in the BE device group, and with an increased rate of post-TAVI aortic regurgitation ≥ grade II (OR 0.98; 95% CI: 0.97-0.99; p = 0.03) in the SE device group. CONCLUSIONS: In transfemoral TAVI, case sequence number influenced mid-term mortality irrespective of prosthesis type, but the learning curve was longer in the case of SE devices.

The effect of the learning curve on paravalvular aortic regurgitation and mid-term mortality in transfemoral transcatheter aortic valve implantation.

OBJECTIVE: Paravalvular aortic regurgitation is an important independent mortality predictor in transcatheter aortic valve implantation (TAVI). Our study evaluated the association between paravalvular aortic regurgitation and mid-term mortality in relation with the learning curve, in patients with severe aortic stenosis who underwent transfemoral TAVI in the first 3 years since the establishment of the program. METHODS: Patients with severe aortic stenosis who underwent transfemoral TAVI between 2017 and 2020 were included in the analysis. Paravalvular aortic regurgitation was assessed by transthoracic echocardiography at 48 hours after the procedure. All-cause mortality was evaluated after 30 days and at mid-term follow-up. RESULTS: Paravalvular aortic regurgitation ≥grade II was associated with mid-term all-cause mortality (OR 4.4; 95%CI 1.82-11.55; p < 0.001), their prevalence declining after the first 60 cases. Baseline characteristics did not significantly differ in the first 60 patients from the rest of the cohort. Male sex (p = 0.006), advanced age (p = 0.04), coronary artery disease (p = 0.003), or elevated STS Score (p = 0.02) influenced mid-term survival. When adjusting for the presence of these factors, only age (OR 1.1; 95%CI 1.0-1.2), paravalvular aortic regurgitation ≥grade II (OR 3.9; 95%CI 1.3-12.9), and the number of days spent in the intensive care unit (OR 1.4; 95%CI 1.1-1.8) were independent predictors of mid-term all-cause mortality. CONCLUSIONS: In a group of patients with severe aortic stenosis who underwent transfemoral TAVI in the first 3 years since the establishment of the program, paravalvular aortic regurgitation ≥grade II was associated with mid-term mortality, both declining after the first 60 cases.

Comparing the First and Second Wave of COVID-19 in Kidney Transplant Recipients: An East-European Perspective.

BACKGROUND: The present study examined whether patient characteristics, management, and outcome of kidney transplant recipients (KTx) with COVID-19 changed in the second versus the first pandemic wave. METHODS: We reviewed all available data (demographics, medical history, comorbidities, therapeutic interventions, and outcome) on our KTx with COVID-19 during the first wave (March-September 2020, n = 33) and the second wave (October 2020-February 2021, n = 149) of the COVID-19 pandemic. RESULTS: One hundred eighty-two out of our 1,503 KTx in active follow-up got COVID-19 during 12-month period, corresponding to a prevalence of 12.1%. No difference was found in age, gender distribution, comorbidities, body mass index, or baseline immunosuppression between the 2 COVID-19 waves. Bilateral COVID pneumonia was more frequent during the first wave. More KTx were managed as outpatients during the second wave (15 vs. 39%, p < 0.01). Calcineurin inhibitors were more sparingly reduced during the second wave, whereas antimetabolites were similarly reduced (91 vs. 86, p = ns). Admission to intensive care units was comparable between the first (27%) and second waves (23%). During the first wave, 8 out of 9 patients (89%) requiring intensive care died, whereas the mortality of the ICU patients in the second wave was 68% (23 deaths) (p = 0.2). The overall mortality was 24% during the first wave and 16% during the second wave (p = 0.21), while in-hospital mortality was identical between the CO-VID-19 waves (27%). Increasing age and poor allograft function were significant predictors of mortality. CONCLUSIONS: Most patient characteristics and outcome were comparable between the first 2 COVID-19 waves. More KTx were managed as outpatients without an overall negative impact on outcome.

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation.

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.

Evaluation of Oxidative Stress Biomarkers, Pro-Inflammatory Cytokines, and Histological Changes in Experimental Hypertension, Dyslipidemia, and Type 1 Diabetes Mellitus.

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.

One year outcomes after small incision lenticule extraction ReLEX in the correction of myopia and myopic astigmatism.

PURPOSE: To report the visual and refractive outcomes of small incision lenticule extraction ReLEX (SMILE) technique using VisuMax femtosecond laser in myopia and myopic astigmatism patients. MATERIAL AND METHODS: A non-randomized clinical study has been conducted on patients with myopia and myopic astigmatism who underwent ReLEX SMILE technique, using the Zeiss VisuMax Laser system (Carl Zeiss Meditec AG, Jena, Germany) at Oculens Clinic, Cluj-Napoca, Romania. Patients older than 18 years, with ocular astigmatism up to -5 diopters (D), spherical equivalent up to -10.00 D, corrected distance visual acuity (CDVA) of 0.3 or better before the surgery, stable refraction for one year, and with a minimum calculated post operator residual stromal bed of 250µ were included in the study. RESULTS: The study involved a total of 25 myopic eyes (median of sphere diopters equal with -4D) and 67 myopic astigmatic eyes (median of cylinder diopters equal with -1.5 D). The mean refractive spherical equivalent (MRSE) on patients with myopic eyes reduced from -4.25D (median) to -0.5D at one month follow-up, -0.25 D at 6 and 12 months. The mean refractive spherical equivalent (MRSE) on patients with astigmatic myopic eyes reduced from-6.25 D to -0.67 D at one month, -0.62 D at six and twelve months. The value of sphere decreased postoperatively on myopic eyes with a median of -0.25D at one, six and twelve months. The value of cylinder decreased postoperatively on myopic astigmatic eyes with a median of -0.50 D at one month, -0.25 D at six months and -0.50 D at 12 months. At 6 and 12 months, 20 (80.0%) of myopic eyes were maintained within ±0.5 D and 22 (88.0%) with ±1D. On both groups (myopic eyes and myopic astigmatic eyes), statistically significant differences were observed when the keratometric baseline values were compared to each follow-up (P-values < 0.0001), without any significant differences between follow-ups (P-values>0.15). At 1-month follow-up, uncorrected distance visual acuity (UDVA) was better than or equal to 0.5 in 88.0% of myopic eyes and 82.1% of myopic astigmatic eyes. UDVA remained stable in all cases of myopic eyes at six months and the percentage increased at 92.0% in myopic eyes. UDVA slightly increased at 6-months (85.1%) and remained at the same value at 12-months in myopic astigmatism eyes. CONCLUSIONS: SMILE proved an effective and safe refractive corneal procedure and provided a predictable and stable correction of myopia and myopic astigmatism. SMILE technique demonstrated very good outcomes in terms of keratometric, cylinder, spherical measurements.

Lockdown, Social Media exposure regarding COVID-19 and the relation with self-assessment depression and anxiety. Is the medical staff different?

INTRODUCTION: Locking the humanity in their homes, COVID-19 forced people to use the technology at hand to keep informed about the outbreak and to keep close to their loved ones. During this time, even if physical health is theoretically unaffected, keeping calm and sane can be challenging. The aim of this research was to evaluate whether exposure to COVID-19 information available in the digital space has a different impact on the mental condition of Romanian medical staff, compared with the general population, particularly searching for depression and anxiety symptoms. MATERIALS AND METHODS: An online survey was conducted from April 6 to 16, 2020 within the Romanian users of Social Media platforms. The questionnaire assessed depression with the WHO-Five Well-Being Index, anxiety with the Generalised Anxiety Disorder Scale and Social Media exposure by asking how often the respondents saw COVID-19 related information on the most popular Social Media channels in Romania. Information about: gender, age, educational level, occupation, area of living and risk category was also collected. The risk categories were defined as no risk, medium risk and medical staff. RESULTS: Almost 90% of the 402 participants received daily through at least one Social Media channel information related to the COVID-19 outbreak. Social Media Exposure significantly associated with the risk group only for Facebook and LinkedIn. However, exposure to information regarding COVID-19 was neither associated with anxiety nor depression. No significant association was identified neither between age class and self-assessed anxiety nor self-assessed depression. The self-assessment of depression was significantly more frequent as compared with the self-assessment of anxiety. CONCLUSION: The results of this research are opposite to most of the already published literature. Depression and anxiety could not be correlated with the context of lockdown and excessive COVID-19-related information.

Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial.

BACKGROUND: Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate. METHODS: This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging. RESULTS: 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent. CONCLUSIONS: The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.

Evidence-based medicine self-assessment, knowledge, and integration into daily practice: a survey among Romanian physicians and comparison between trainees and specialists.

BACKGROUND: A gap between the attitude towards evidence-based medicine (EBM), knowledge and awareness has been reported among physicians from different parts of the world. However, no investigation on Romanian physicians is available in the scientific literature. Our study aimed, firstly, to assess EBM awareness and the knowledge used by Romanian physicians, and, secondly, to compare resident trainees with specialists. METHODS: Romanian trainee and specialist physicians were invited to participate in this cross-sectional study. The study tool was an online questionnaire designed to explore their awareness, knowledge, usefulness, the attitude in medical documentation, and the use of professional EBM resources. Data were collected by Google Form from January 1st to April 30th, 2017, respecting the responders' anonymity. Two groups of physicians were investigated as trainees and specialists, respectively. Descriptive statistics (number, percentage, median and interquartile range) was used to describe the survey-related variables. Statistical significance on qualitative data was calculated with the Chi-square test, Fisher's exact test, or the Z-test for proportions. RESULTS: Two hundred and 50 physicians participated in this study (68% trainees vs. 32% specialists). In both groups, a significantly high percentage was represented by women as compared to men (trainees 72.4%, specialists 70%). The correct definition of EBM was identified by most respondents (75.6%). Affirmatively, both trainees and specialists always looked at levels of evidence when reading scientific literature, but a small percentage (6.5% trainees and 3% specialists) adequately identified the uppermost types of evidence in the hierarchy. Almost a quarter of the respondents shared the name of mobile EBM resources that they used to support the daily practice. Only six out of the 49 listed mobile resources met the EBM criteria. CONCLUSIONS: The participants proved to have limited knowledge of EBM and a positive attitude towards the concept. They made use of mobile medical resources without understanding which of these were evidence-based.

Diagnostic Criteria of Oral Lichen Planus: A Narrative Review.

Oral lichen planus (OLP) is a disease with unclear etiology or pathogenesis, categorized by the World Health Organization as oral lichenoid lesions (OLL; interface mucositis or lichenoid mucositis) into a group of potentially malignant disorders. The diagnosis of OLP is challenging because the clinical and histopathologic features are frequently seen in OLP, OLL and/or other mucosal diseases with lichenoid characteristics. Furthermore, OLP has a dynamic nature. Finally, an early and precise diagnosis can play a decisive role, allowing timely treatment and thus improving the patient quality of life. This article summarizes the state-of-the-art regarding OLP and OLL and discusses the challenges faced on making an accurate diagnosis, aiming to provide a practical guideline for the postgraduates and oral physicians in reaching the diagnosis of these lesions.

Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine.

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes.

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus.

Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.

Is Scientific Medical Literature Related to Endometriosis Treatment Evidence-Based? A Systematic Review on Methodological Quality of Randomized Clinical Trials.

Background and objectives: Informed decision-making requires the ability to identify and integrate high-quality scientific evidence in daily practice. We aimed to assess whether randomized controlled trials (RCTs) on endometriosis therapy follow methodological criteria corresponding to the RCTs' specific level in the hierarchy of evidence in such details to allow the reproduction and replication of the study. Materials and Methods: Using the keywords "therapy" and "endometriosis" and "efficacy" three bibliographic databases were searched for English written scientific articles published from 1 January 2008 to 3 March 2018. Only the randomized clinical trials (RCTs) were evaluated in terms of whether they provided the appropriate level of scientific evidence, equivalent to level 1, degree 1b in the hierarchy of evidence. A list of criteria to ensure study replication and reproduction, considering CONSORT guideline and MECIR standards, was developed and used to evaluate RCTs' methodological soundness, and scores were granted. Three types of bias, namely selection bias (random sequence generation and allocation concealment), detection bias (blinding of outcome assessment), and attrition bias (incomplete outcome data) were also evaluated. Results: We found 387 articles on endometriosis therapy, of which 38 were RCTs: 30 double-blinded RCTs and 8 open-label RCTs. No article achieved the maximum score according to the evaluated methodological criteria. Even though 73.3% of the double-blinded RCTs had clear title, abstract, introduction, and objectives, only 13.3% provided precise information regarding experimental design and randomization, and also showed a low risk of bias. The blinding method was poorly reported in 43.3% of the double-blinded RCTs, while allocation concealment and random sequence generation were inadequate in 33.3% of them. Conclusions: None of the evaluated RCTs met all the methodological criteria, none had only a low risk of bias and provided sufficient details on methods and randomization to allow for the reproduction and replication of the study. Consequently, the appropriate level of scientific evidence (level 1, degree 1b) could not be granted. On endometriosis therapy, this study evaluated the quality of reporting in RCTs and not the quality of how the studies were performed.

A View of Human Immunodeficiency Virus Infections in the North-West Region of Romania.

Background and objectives: In Romania, the human immunodeficiency virus (HIV) epidemic is almost the same as it is in Central Europe, with some differences; particularity the following one: people with nosocomial HIV infection, also known as Romanian cohort. Aim: The study aimed to present a local view of HIV infection in the North-West part of Romania, and to identify the particularities of patients under medical care in the Cluj AIDS Center. Materials and Methods: The demographic characteristics (age and gender), and medical and epidemiological data (stage of HIV infection and mode of transmission) of patients in a medical care in the Cluj Acquired Immunodeficiency Syndrome (AIDS) Center were evaluated. Data from the first patients admitted between 1989 and 2018, and the statuses of the infected persons as per 31 December 2018 were analyzed. Results: Nine hundred and fourteen patients were included in the study. The patients' ages varied from 0 (newborns from HIV-infected mothers) to 72 years old, and most patients were men (596 men vs. 318 women). The main mode of transmission was sexual (>50%), with an increased number of men who have sex with men (MSM) in the last years (from two cases in 2006 to thirty-four cases in 2018), and a very small percentage of intravenous drug users (IDU; <1%). The patients from the Romanian cohort were more frequently women as compared with men (p-value <0.0001), women were more frequently later presenters than men (p-value <0.0001), and the women more frequently had candidosis (p-value = 0.0372), cerebral toxoplasmosis (p-value = 0.0404), and co-infection with hepatitis B virus (p-value = 0.0018). One hundred and sixty patients died by the end of 2018 (17.5%). Sixty-eight children had been born from HIV-infected mothers, and 17 were HIV infected (25%). Conclusion: The main mode of HIV transmission in our sample was sexual, with an increased number of MSM over the last years and a low number of cases of intravenous drug users. A quarter of children borne from HIV-infected mothers were HIV infected.

Vitamin D deficiency, insulin resistance and thyroid dysfunction in obese patients: is inflammation the common link?

The aim of this article is to study the possible relation of serum vitamin D concentrations to body mass index (BMI), visceral fat thickness (VFT), insulin resistance (IR), inflammation (serum monocyte chemoattractant protein-1 - MCP-1) and thyroid parameters in obese patients. A total of 158 non-diabetic, obese patients aged 19-68 without a history of thyroid pathology were recruited. Biochemical markers, insulin, 25-OH vitamin D, thyroid parameters (TSH, FT3, FT4, TPO antibodies, TG antibodies) and VFT were measured. Serum MCP-1 evaluated the inflammation. A HOMA-IR cut-off value of 2.5 defined IR. Most patients had severe (70.3%) or moderate (25.3%) vitamin D deficiency. Vitamin D level was negatively associated with BMI (p = .043) and during the cold season with VFT (p = .009). Vitamin D deficiency correlated with Hashimoto's thyroiditis prevalence during the warm season (p = .047) and was a risk factor for its occurrence (p = .021). At 15 ng/mL cut-off value, vitamin D was negatively correlated with MCP-1 (p = .0006). Also, MCP-1 was positive correlated with HOMA- IR (p = .042), TPO-Ab levels (p = .011) and with Hashimoto's thyroiditis (p = .027). MCP-1 was a risk factor for vitamin D deficiency (p < .0001). Our study supports a bidirectional interaction between vitamin D and systemic inflammation in obese patients. Moreover, systemic inflammation is related to the severity and frequency of Hashimoto's thyroiditis. Vitamin D deficiency is the single independent factor associated with Hashimoto's thyroiditis in obese patients.