FibroScan® versus Biochemical Scores: A Study of Liver Fibrosis in HIV with HBV Co-Infection.

The study aimed to determine liver fibrosis in human immunodeficiency virus (HIV) positive individuals using transient elastography (FibroScan®), Fibrosis-4 (FIB-4) score, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) in the HIV Department from Infectious Diseases Hospital "Victor Babeș" Craiova, Romania. Of the analyzed HIV-positive subjects (n = 161), 93 (57.76%) had HIV mono-infection, and 68 (42.24%) had Hepatitis B Virus (HBV) co-infection. The prevalence of advanced liver fibrosis was higher (F2: 11.76% and F3: 13.24%, F4: 4.41%) in the HIV-HBV co-infected group compared to the HIV mono-infected group. The univariate and multivariate analysis identified HBV co-infection (OR = 5.73) male sex (OR = 5.34), serum aspartate amino-transferase levels (Pearson's rho = 0.273), low platelet count (Pearson's rho = -0.149) and erythrocyte sedimentation rate (OR = 1.030) as risk factors for the presence of liver fibrosis. Body mass index (OR = 1.08), serum lipid levels (OR = 0.96), viral load at diagnosis (OR = 1.00005), and low CD4+ cell count (OR = 0.977) were also correlated with liver fibrosis. The FIB-4 and APRI scores were strongly correlated with each other. In conclusion, HBV co-infection seems to be a determinant factor for liver fibrosis development in people living with HIV, together with other risk factors.

Seroprevalence of Herpes Simplex Virus Types 1 and 2 among Pregnant Women in South-Western Romania.

BACKGROUND: Pregnancy-related infections with the human herpes simplex virus (HSV) strains HSV-1 and HSV-2 are particularly noteworthy. There are numerous reported examples of intrapartum transmission of herpes infection, notwithstanding the extreme rarity of intrauterine transfer from mother to fetus. The purpose of this study was to evaluate the seroprevalence of HSV-1 and HSV-2 antibodies in pregnant women in the western region of Romania. METHODS: Pregnant women who presented for routine pregnancy monitoring at Romania's County Clinical Emergency Hospital in Craiova between 2013 and 2016 and 2019 and 2022 were included in the study. In order to find anti-HSV-1/2 IgG antibodies, we conducted serological testing on the patients and gathered demographic information from them. RESULTS: HSV-1 seroprevalence was shown to have declined in rural areas and increased in urban areas, with values between 2013 and 2016 being 89.30% and those between 2019 and 2022 being 84.96%, respectively. Women over 35 who were pregnant had the highest seroprevalence. The seroprevalence of HSV-2 decreased from 16.16% in 2013-2016 to 12.43% in 2019-2022, and both rural and urban areas continued to experience this declining trend. Similarly, pregnant women over 35 years old had the highest frequency of HSV-1 infections. CONCLUSIONS: Establishing educational programs and other actions to reduce the transmission rate and ultimately the prevalence of the disease can be made easier with knowledge about the seroprevalence of HSV-1 and HSV-2 infections.

Bacterial and Fungal Keratitis in a Tertiary Care Hospital from Romania.

Infectious keratitis is a significant global problem that can lead to corneal blindness and visual impairments. This study aimed to investigate the etiology of infectious bacterial and fungal keratitis, identify the causative pathogens and their antimicrobial resistance patterns, and analyze the risk factors associated with the development of infectious keratitis. The study was observational and retrospective, involving 226 eyes from 223 patients presented at the Ophthalmology Clinic of the County Clinical Emergency Hospital of Craiova, Romania. The inclusion criteria included corneal ulceration/abscess/infiltrate present on slit-lamp examination and positive microbiological sampling for bacteria or fungi. The study found that the most common causes of infectious keratitis were coagulase-negative staphylococci (35.40%), Staphylococcus aureus (11.06%), and Pseudomonas aeruginosa (14.16%). The Gram-positive bacteria showed high resistance rates to penicillin, moderate rates to gentamycin and clindamycin, and low resistance to chinolones. The Gram-negative bacteria were highly resistant to ampicillin and amoxicillin-clavulanic acid, while third-generation cephalosporins, quinolones, and carbapenems were effective. Systemic antibiotics, such as vancomycine, piperacillin-tazobactam, amikacin, and ceftazidime, show promise against keratitis with low resistance rates, whereas carbapenems and topical aminoglycosides had higher resistance, leaving moxifloxacin as a potential topical option for Gram-positive bacteria and Pseudomonas aeruginosa, albeit with resistance concerns for Klebsiella spp. Although fungal keratitis was rare, Fusarium spp. and Candida albicans were the leading fungal pathogens, with incidences of 2.65% and 2.21%, respectively. Candida albicans was broadly susceptible to most antifungals, while Fusarium solani, Curvularia lunata, and Alternaria alternata exhibited resistance to many antifungals. Amphotericin B and caspofungin can be used as systemic antifungals in fungal keratitis. The study also identified risk factors for keratitis such as ocular trauma (65.92%, OR: 2.5), contact lens wear (11.94%, OR: 1.8), and corneal scarring/leukoma (10.17%, OR: 1.6). Keratitis was more frequent in individuals over 60 years old. The findings of this study have implications for the development of effective diagnostic, therapeutic, and preventive strategies for infectious keratitis.

Pre- and Post-COVID-19 Antimicrobial Resistance Pattern of Pathogens in an Intensive Care Unit.

We aimed to determine the trend of the antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU) in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. Positive bacterial culture data from 1695 samples from the pre-COVID-19 period and 1562 samples from the post-COVID-19 period were obtained. The most frequently isolated bacteria in both periods were Staphylococcus aureus and Klebsiella spp. The resistance rates of Klebsiella spp. Significantly increased against colistin (0.38% to 20.51%), gentamicin (44.62% to 64.85%), and aztreonam (56.35% to 3.60%). There was a significant increase in the resistance rate against colistin for E. coli strains (4.69% to 32.46%) and for Acinetobacter sp. strains (3.37% to 18.09%). More than 50% of the Staphylococcus aureus strains were MRSA, with statistically significant increases in the antimicrobial resistance rate against doxycycline (40.08% to 51.72%), linezolid (0.22% to 3.13%), rifampicin (53.16% to 64.93%), and teicoplanin (26.31% to 53.40%). The study revealed a significantly increasing trend in the antimicrobial resistance rate of Gram-negative pathogens against certain antibiotics, including those used only in cases where there are no other therapeutic options.

Seroprevalence of Anti-Cytomegalovirus Antibodies in Pregnant Women from South-West Romania.

Cytomegalovirus (CMV), in addition to other agents, is part of the TORCH complex (Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex viruses, and other agents). CMV infection is the most frequent cause of congenital malformations. This study aimed to establish the variation of prevalence of anti-CMV antibodies in pregnant women from the South-West region of Romania, according to demographic factors, such as age and area of residence, in two separate time periods (2013-2016 and 2019-2022). We collected from the hospital records the age, place of residence, and anti-CMV antibody test results using immune electrochemiluminescence and chemiluminescence. This study found that the seroprevalence of anti-CMV IgM antibodies increased slightly from 2013-2016 to 2019-2022, from 1.92% to 2.26%, and for IgG antibodies from 93.68% to 94.96%. In both groups was observed a descending trend of anti-CMV IgM seroprevalence with an increase in age, showing a decrease in seroprevalence from 3.57% to 1.09% in pregnant women from rural areas in the 31-35 years age group, while in urban areas, we observed a decrease in seroprevalence from 11.11% to 3.06% in the <20 years age group. The IgG seroprevalence showed an increase both in rural areas (from 93.97% to 95.52%) and urban areas (from 93.52% to 94.27%). In both groups, seroprevalence was higher in rural areas compared to urban regions. These results show a high rate of immunization against CMV in pregnant women in South-West Romania, which led to a low risk of acquiring the primary infection during pregnancy. However, the increase in the rate of primary CMV infections in pregnancy suggests the need for prioritizing screening programs and improving the existing protocols to enhance maternal and child healthcare.

Research on the Influence of MUVON PLUS Treatment Upon the Biomechanical Behavior of the Human Osteoarthritic Knee.

BACKGROUND: This study aimed to investigate the effects of MUVON PLUS, a dietary supplement containing hydrolized collagen, chondroitin sulfate, and vitamin C, on the biomechanical behavior of the knee joint in patients with second-degree osteoarthritis (OA). MATERIAL AND METHOD: The study included 15 participants who underwent biomechanical testing before and after 3 and 6 months of supplement administration. Biometrics and SimiMotion software were used to process and analyze the data. Results showed significant improvements in biomechanical parameters such as joint range of motion, joint torque, and joint stiffness for all patients during the treatment. Improvements were observed across various tests, including horizontal walking, stairs climbing and descending, sitting/standing up from a chair, and knee squats. This improvement in biomechanical performance was also reflected in the patients' reported quality of life. For the stairs climbing test, the maximum flexion-extension angle increased by approximately 7% after 3 months and 12% after 6 months. In the stairs descending test, the maximum flexion-extension angle increased by approximately 8% after 3 months and 19% after 6 months. These results highlight an improvement in mobility for the study participants. CONCLUSIONS: Significant improvements of the biomechanical parameters of the knee joint were found in all patients during the treatment with the MUVON PLUS in all tests, which indicates the clear clinical benefit, revealed by improving the quality of life reported by patients. Overall, the study demonstrated the effectiveness of MUVON PLUS in enhancing the biomechanical behavior of the knee joint in patients with OA, providing valuable insights for future research and treatment.

Toxoplasma gondii Seroprevalence and Trends in Women Presenting for Toxoplasma Screening in South-West Romania.

Toxoplasmosis, caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii), is a globally prevalent zoonotic disease with potentially severe implications for immunocompromised individuals, pregnant women, and their fetuses/children. This study examined the prevalence of anti-T. gondii IgM and IgG antibodies in two groups of childbearing age women, including 653 participants in Group 1 (2013-2016) and 3221 participants in Group 2 (2019-2022). Our results revealed a decrease in the overall positivity rate of anti-T. gondii IgM antibodies from 2.32% to 1.06%, suggesting improved public health interventions over time. However, there were variations among different age groups and between rural and urban environments, with a significant decrease in urban areas across all age groups from Group 1 to Group 2. Regarding anti-T. gondii IgG antibodies, we did not observe a significant change in the seropositivity rate between the two groups. In the rural population with an age group over 35 years, we observed the highest positivity rate in Group 2. This study provided information on the risk factors and burden of toxoplasmosis in women of childbearing age with data that can be valuable to public health policies and the planning of healthcare measures for effective toxoplasmosis management.

Seroprevalence of Infections with TORCH Agents in Romania: A Systematic Review.

Maternal-fetal infectious pathology-notably the TORCH panel (Toxoplasma gondii, rubella, Cytomegalovirus, and herpes simplex viruses)-critically impacts maternal and neonatal health. This review collates data on the seroprevalence of IgG and IgM antibodies against TORCH agents in Romanian women, aiming to discern regional and population differences and identify risk factors. Twenty studies were included in the review, revealing variable seroprevalence rates across the country. Regions such as Moldavia and Banat showed higher anti-T. gondii IgG seroprevalence rates than Bihor, with notable declines in Banat. Rural, older, and multiparous women showed elevated T. gondii IgG rates. Anti-rubella vaccine introduction significantly reduced the prevalence of anti-rubella IgG antibodies, but recent vaccination coverage decreases raise concerns. CMV and HSV seroprevalence varied geographically, with rural areas generally showing higher CMV rates and HSV influenced by factors like education level and number of sexual partners. Concurrent seroprevalence of multiple TORCH components in some cases underscores potential common risk factors. This study highlights the importance of continuous monitoring and preventive measures such as vaccinations and awareness campaigns to mitigate the health impact on the pregnant population.

Factors Contributing to Surgical Site Infections: A Comprehensive Systematic Review of Etiology and Risk Factors.

Surgical site infections persist as a substantial concern within the realm of hospital-acquired infections. This enduring issue is further compounded by the mounting challenge of antibiotic resistance, a surge in surgical interventions, and the presence of comorbidities among patients. Thus, a comprehensive exploration of all discernible risk factors, as well as proactive preventive and prophylactic strategies, becomes imperative. Moreover, the prevalence of multidrug-resistant microorganisms has reached alarming proportions. Consequently, there is an acute need to investigate and scrutinize all potential therapeutic interventions to counter this burgeoning threat. Consequently, the primary objective of this review is to meticulously assess the origins and risk elements intertwined with surgical site infections across a diverse spectrum of surgical procedures. As the medical landscape continues to evolve, this critical analysis seeks to provide a nuanced understanding of the multi-faceted factors contributing to surgical site infections, with the overarching aim of facilitating more effective management and mitigation strategies. By exploring these dimensions comprehensively, we endeavor to enhance patient safety and the quality of surgical care in this era of evolving healthcare challenges.

ELTD1 Review: New Regulator of Angiogenesis in Glioma.

Glioblastoma (GBM) is a severe brain cancer in which angiogenesis is controlled by G protein-coupled receptors (GPCRs), such as Epidermal Growth Factor Latrophilin and seven transmembrane domain-containing protein 1 (ELTD1), which are crucial for tumor progression. ELTD1 is an understudied GPCR with a broad expression profile in various tissues, including the human brain, especially in the cerebral cortex. It plays a significant role in angiogenesis and tumorigenesis and is regulated by interconnected VEGF and DLL4/Notch pathways. ELTD1 also modulates the JAK/STAT3/HIF-1α signaling axis, affecting the response of cells to low-oxygen conditions and promoting cell proliferation. However, their specific ligands and functional mechanisms remain unclear. ELTD1 expression is associated with different outcomes in various cancers. For example, in GBM, higher ELTD1 levels are linked to more mature and less leaky blood vessels, potentially enhancing drug delivery and therapeutic success. It also has divergent prognostic implications in renal, ovarian, and colorectal cancer. Additionally, ELTD1 overexpression in central nervous system endothelial cells suggests that it is a potential biomarker for multiple sclerosis. Therapeutically, blocking ELTD1 inhibits vessel formation, possibly slowing tumor growth. Initial therapies used polyclonal antibodies, but the shift has been towards more targeted monoclonal antibodies, particularly in preclinical glioma models. This review aimed to translate these insights into effective clinical treatments. However, several gaps remain in our knowledge regarding ELTD1 ligands and their potential involvement in other physiological or pathological processes that future research can address to elucidate the role of ELTD1 in cancer, through angiogenesis and other intracellular pathways.

Prevalence of Multidrug-Resistant Pathogens Causing Bloodstream Infections in an Intensive Care Unit.

Introduction: Bloodstream infections are the most severe infections that cause the highest mortality rate, especially in patients admitted to the intensive care unit (ICU). In this study, we aimed to analyze the distribution, resistance patterns and prevalence of MDR (multidrug-resistant) pathogens isolated in blood samples collected from patients with severe invasive infections hospitalized in the ICU. Methods: A retrospective study of bacterial pathogens was performed on 490 patients admitted to the ICU between 2017 and 2020. The resistance patterns were analyzed using Vitek 2 Compact system. Results: In total, 617 bacterial isolates were obtained. Four hundred and twenty-seven isolates (69.21%) were Gram positive and 190 isolates (30.79%) were Gram negative bacteria. The most frequently isolated micro-organisms identified in the blood samples for the entire period (2017-2020) were Coagulase-negative staphylococci (CoNS) (318-51.54%), followed by Klebsiella pneumoniae (70-11.34%), Methicillin-Resistant Staphylococcus aureus (MRSA) (58-9.40%), Acinetobacter baumannii (45-7.29%) and Enterococcus faecalis (42-6.80%). The number of Klebsiella pneumoniae strains significantly increased in 2020, compared to the previous year (p < 0.05). The Acinetobacter baumannii prevalence was significantly higher in the age group of 20-64 years (10.89%) and over 65 years (3.53%) (p < 0.001). The difference between the prevalence of CoNS in the elderly (67.84%) and in adults (20-64 years) (52.47%) was also statistically significant (p < 0.001). High rates of MDR were found for Acinetobacter baumannii (97.77%), Pseudomonas aeruginosa (65%), Klebsiella pneumoniae (50%), Enterococcus faecalis (47.61%) and MRSA (46.55%). More than 60% of the Klebsiella pneumoniae strains were found to be resistant to carbapenems. Conclusion: The study revealed an alarming prevalence of MDR strains isolated in blood samples of the patients admitted to the ICU, indicating the necessity of consistent application of the measures to control.

A Rare Case of Endophthalmitis with Rhizobium radiobacter, Soon after a Resolved Keratitis: Case Report.

BACKGROUND: Rhizobium (Agrobacterium) species are plant aerobic bacteria, which in some cases can produce endophthalmitis in humans after corneal trauma. CASE PRESENTATION: A 42-year-old female patient presented in the Emergency Department of the Emergency County Hospital of Craiova, Romania, reporting pain, epiphora, and blurry vision in her right eye for about five days. This initial infectious keratitis episode was successfully resolved, but after 20 days she presented again after trauma with a leaf with corneal abscess. In the conjunctival secretion, R. radiobacter was identified. Despite antibiotherapy, the patient's state did not improve, and ultimately the eye was eviscerated. METHODS: A search was performed in the ProQuest, PubMed, and ScienceDirect databases for the terms Agrobacterium, Rhizobium, radiobacter, and eye. We eliminated non-human studies, editorials and commentaries, and non-relevant content, and excluded the duplicates. RESULTS: In total, 138 studies were initially obtained, and then we selected 26 studies for retrieval. After the selection process, we ended up including 17 studies in our analysis. Most studies reported R. radiobacter endophthalmitis after ocular surgical procedures or outdoor activities that involve exposure to soil. CONCLUSION: R. radiobacter is a rare cause of endophthalmitis after eye trauma that generally responds well to usual antibiotherapy, but occasionally can evolve to severe, leading to the loss of the eye.

TEM,CTX-M,SHV Genes in ESBL-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Clinical Samples in a County Clinical Emergency Hospital Romania-Predominance of CTX-M-15.

BACKGROUND: CTX-M betalactamases have shown a rapid spread in the recent years among Enterobacteriaceae and have become the most prevalent Extended Spectrum Beta-Lactamases (ESBLs) in many parts of the world. The introduction and dissemination of antibiotic-resistant genes limits options for treatment, increases mortality and morbidity in patients, and leads to longer hospitalization and expensive costs. We aimed to identify the beta-lactamases circulating encoded by the genes blaCTX-M-15, blaSHV-1 and blaTEM-1 in Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) strains. Furthermore, we established the associated resistance phenotypes among patients hospitalized in the Intensive Care Unit (ICU) from County Clinical Emergency Hospital of Craiova, Romania. METHODS: A total of 46 non-duplicated bacterial strains (14 strains of E. coli and 32 strains of K. pneumoniae), which were resistant to ceftazidime (CAZ) and cefotaxime (CTX) by Kirby-Bauer disk diffusion method, were identified using the automated VITEK2 system. Detection of ESBL-encoding genes and other resistance genes was carried out by PCR. RESULTS: E. coli strains were resistant to 3rd generation cephalosporins and moderately resistant to quinolones, whereas K. pneumoniae strains were resistant to penicillins, cephalosporins, and sulfamides, and moderately resistant to quinolones and carbapenems. Most E. coli strains harbored blaCTX-M-15 gene (13/14 strains), a single strain had the blaSHV-1 gene, but 11 strains harbored blaTEM-1 gene. The mcr-1 gene was not detected. We detected tet(A) gene in six strains and tet(B) in one strain. In K. pneumoniae strains we detected blaCTX-M-15 in 23 strains, blaSHV-1 in all strains and blaTEM-1 in 14 strains. The colistin resistance gene mcr-1 was not detected. The tetracycline gene tet(A) was detected in 11 strains, but the gene tet(B) was not detected in any strains. CONCLUSIONS: The development in antibiotic resistance highlights the importance of establishing policies to reduce antibiotic use and improving the national resistance surveillance system in order to create local antibiotic therapy guidelines.

Should all patients with a culture-negative periprosthetic joint infection be treated with antibiotics? : a multicentre observational study.

AIMS: The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. METHODS: A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. RESULTS: None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). CONCLUSION: When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183-188.

COVID-19 and Artificial Intelligence: An Approach to Forecast the Severity of Diagnosis.

(1) Background: The new SARS-COV-2 pandemic overwhelmed intensive care units, clinicians, and radiologists, so the development of methods to forecast the diagnosis' severity became a necessity and a helpful tool. (2) Methods: In this paper, we proposed an artificial intelligence-based multimodal approach to forecast the future diagnosis' severity of patients with laboratory-confirmed cases of SARS-CoV-2 infection. At hospital admission, we collected 46 clinical and biological variables with chest X-ray scans from 475 COVID-19 positively tested patients. An ensemble of machine learning algorithms (AI-Score) was developed to predict the future severity score as mild, moderate, and severe for COVID-19-infected patients. Additionally, a deep learning module (CXR-Score) was developed to automatically classify the chest X-ray images and integrate them into AI-Score. (3) Results: The AI-Score predicted the COVID-19 diagnosis' severity on the testing/control dataset (95 patients) with an average accuracy of 98.59%, average specificity of 98.97%, and average sensitivity of 97.93%. The CXR-Score module graded the severity of chest X-ray images with an average accuracy of 99.08% on the testing/control dataset (95 chest X-ray images). (4) Conclusions: Our study demonstrated that the deep learning methods based on the integration of clinical and biological data with chest X-ray images accurately predicted the COVID-19 severity score of positive-tested patients.

Prevalence and Antimicrobial Resistance of Klebsiella Strains Isolated from a County Hospital in Romania.

The study evaluated the evolution of the incidence of infections with Klebsiella in the County Clinical Emergency Hospital of Craiova (SCJUC), Romania. Also, we monitored antibiotic resistance over more than two years and detected changes in resistance to various antimicrobial agents. Our study included 2062 patients (823 women and 1239 men) hospitalised in SCJUC during the period 1st of September 2017 to 30 June 2019. In 458 patients (22.21%) from the 2062 total patients, the collected samples (1116) were positive and from those, we isolated 251 strains of Klebsiella spp. We conducted a longitudinal analysis of the prevalence of Klebsiella spp. over calendar months, which showed a prevalence in surgical wards that ranged between 5.25% and 19.49% in June 2018, while in medical wards the variation was much wider, between 5.15% and 17.36% in April 2018. Klebsiella spp. strains showed significant resistance to Amoxicillin/Clavulanate, Aztreonam and Cephalosporins such as Ceftriaxone, Ceftazidime and Cefepime. We examined the possible link with the consumption of antibiotics in the same month by performing a multiple linear regression analysis. The evolution of antibiotic resistance in Klebsiella was correlated with the variation of resistance in other bacteria, which suggests common resistance mechanisms in the hospital environment. By performing the regression for dependency between antibiotic resistance and antibiotic consumption, we observed some correlations between antibiotic consumption and the development of antibiotic resistance after 1, 2 and even 3 months (e.g., resistance to meropenem was influenced by the consumption in the hospital ward of imipenem 1 month and two months before, but only 1 month before by the consumption of meropenem). The clustering of strains showed filiation between multiresistant Klebsiella spp. strains isolated from specific patients from the ICU. The evolution of prevalence and antibiotic resistance in Klebsiella correlated with the resistance in other bacteria, which suggest common resistance mechanisms in the hospital environment, and also with the consumption of antibiotics.

Detrimental effects of 6 months exposure to very low doses of a mixture of six pesticides associated with chronic vitamin deficiency on rats.

This study aimed to evaluate the long-term low-dose effects of exposure to a mixture of 6 pesticide active substances (diquat, imazamox, imazethapyr, tepraloxydin, bentazone, acifluorfen) and to elucidate if chronic vitamin deficiency can influence their toxicity. Two hundred Wistar rats were divided in 4 groups: a vitamin-sufficiency control group, a vitamin-deficiency control group, a vitamin sufficiency test group and a vitamin-deficiency test group. The test groups were treated with the aforementioned pesticides at doses 100 times lower than the corresponding NOAEL. After 6 months, ten rats from each group were sacrificed and a complete evaluation of blood and urine biochemistry, biomarkers of oxidative stress, xenobiotic detoxification enzymes and lysosomal enzymes and organ histopathology was performed. The pesticides mixture and vitamin deficiency determined an increase in alkaline phosphatase levels and urinary calcium levels, abnormal serum lipid profile, and a decrease of total blood proteins levels, red blood cells, haematocrit and haemoglobin. The combination of the two stressors up-regulated CYP1A1, CYP1A2, CYP2B1 and GST levels. This study provides a new proof for the need to move forward from single chemical testing to a more complex approach to account for the multitude of stressors that can challenge the setting of real safety levels.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

A new threat from an old enemy: Re­emergence of coronavirus (Review).

The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus­associated disease, the spread and lethality of the 2019 outbreak (COVID­19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

Behavioral impacts of a mixture of six pesticides on rats.

Pesticides can potentially contribute to the development of numerous neurodegenerative diseases. This study evaluates the effects of a six-pesticide mixture at doses around the no-observed-adverse-effectlevels (0 × NOAEL, control) and 0.25, 1 and 5 × NOAEL on behavior of Wistar rats. After 3, 6 and 12 months, rats were observed for neurobehavioral changes using the techniques of elevated plus maze and universal problemchamber, and the experiment was conducted thrice. The 3-month exposure revealed a decrease in the cognitive ability at the dose of 5 × NOAEL, and a dose-dependent research activity and anxiety. The 6-month exposurerevealed non-monotonic effects on the cognitive ability, with a decrease by 0.25 and 5 × NOAEL, as well as non-monotonic effects on anxiety, withan increase by 0.25 and 1 × NOAEL. A decrease was also observed in research activity at 5 × NOAEL. However, the 12-month exposure resulted to an increase in cognitive ability by 0.25 × NOAEL and in anxiety by 1 × NOAEL, as well as to a dose-dependent research activity. Repeating the trial showed that the cognitive ability increased from one trial to another, while the researching activity decreased and the anxiety increased by 0× NOAEL. In the groups exposed to pesticides mixture, the trends were different, showing that the exposure to pesticides combined with repeated trials, also influence the response of the animals. The resultsdemonstrate the occurrence of several dose-dependent behavioral responses, with negative effects occurring at doses that are considered safe. This study provides novel insights about time-dependent mixtures biology, and an important perspective to consider when conducting risk assessments.