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K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the last three years, in the period of intense population aging, migrations and climate changes in Europe and Croatia as well, we observed changes in antibiotic resistance patters of carbapenem-resistant K. pneumoniae (CRKP) isolates obtained routinely in community and inpatient setting. The aim was to compare and subsequently analyze CRKP hospital and community isolates resistance mechanisms, traits and molecular epidemiology, in order to analyze the dynamic of resistance trends, carbapenemase types and plasmid epidemiology. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV (OXA-48, KPC, NDM, VIM) testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. IncL, associated with OXA-48, was the dominant plasmid type. No significant differences in the resistance profile and resistance determinants were found between hospital and community isolates plasmid type. The predominance of OXA-48 carbapenemase is in line with the reports from the neigbouring countries. [ABSTRACT FROM AUTHOR]

Objective: Bacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA). Methods: All studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. Results: Weincluded42studies thatmetthecriteria, involving a total of8382patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI1.63-9.98), theadverse reaction rateofprobioticsgroupwaslowerthanthat of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Directmeta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88). Conclusions: The results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future. [ABSTRACT FROM AUTHOR]

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425. [ABSTRACT FROM AUTHOR]

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Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive care units in a tertiary referral hospital was conducted. The study aimed to characterize β-lactamases and other resistance traits of Gram-negative bacteria isolated in surgical intensive care units (ICUs). Disk diffusion and the broth dilution method were used for antibiotic susceptibility testing, whereas ESBL screening was performed through a double disk synergy test and an inhibitor-based test with clavulanic acid. A total of 119 MDR bacterial isolates were analysed. ESBL production was observed in half of the Proteus mirabilis, 90% of the Klebsiella pneumoniae and all of the Enterobacter cloacae and Escherichia coli isolates. OXA-48 carbapenemase, carried by the L plasmid, was detected in 34 K. pneumoniae and one E. coli and Enterobacter cloacae complex isolates, whereas NDM occurred sporadically and was identified in three K. pneumoniae isolates. OXA-48 positive isolates coharboured ESBLs belonging to the CTX-M family in all but one isolate. OXA-23 carbapenemase was confirmed in all A. baumannii isolates. The findings of this study provide valuable insight of resistance determinants of Enterobacterales and A. baumannii which will enhance surveillance and intervention strategies that are necessary to curb the ever-growing carbapenem resistance rates. [ABSTRACT FROM AUTHOR]

Background: The fecal carriage of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) is a major driver of the global spread of these antibiotic resistance determinants. Here we determined the rate of fecal ESBL-PE carriage in pediatric hospitals and community-serving healthcare centers serving adults and children in the Gaza Strip, Palestine. Methods: A total of 373 fecal and rectal samples were collected from different hospitals and clinics in Gaza. The antibiotic susceptibility was determined using the disk diffusion method and interpreted according to CLSI guidelines. The bacterial isolates were tested for ESBL production using phenotypic methods (double disk synergy test and growth on selective chromogenic media). BlaCTX−M, blaSHV, and blaTEM genes were sought by PCR. Results: Out of the 373 isolates tested, 138 (37%) were considered ESBL positive as revealed by phenotypic tests. The prevalence of ESBLs among hospitalized patients was 39.1% (hospital setting) whereas, among outpatients attending community healthcare centers, it was 35.1% (community setting). ESBL production among Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Proteus mirabilis, and Klebsiella aerogenes isolates was 52.8%, 39.1%, 26.7%, 2.8%, and 2.1% respectively. Meropenem and amikacin were the most effective antibiotics against ESBL producers (68.9% and 73.6% susceptibility, respectively), while only 15.2%, 22.5%, and 24.6% remained susceptible to ceftazidime, cefotaxime, and ceftriaxone, respectively. Out of 138 phenotypically ESBL-positive isolates, 98 randomly chosen were screened for blaCTX−M, blaTEM, and blaSHV genes. The prevalence rate of blaCTX−M was 45.9%, while blaTEM and blaSHV genes were detected in 16.8% and 5.2% of CTX-M-negative isolates (corresponding mostly for K. pneumoniae isolates in the case of SHV-PCR), respectively. Conclusions: The study revealed an alarmingly high prevalence of fecal carriage of ESBL-producing Enterobacterales among hospitalized children but also in the community of the Gaza Strip. In addition, 30% of ESBL-producers were already resistant to carbapenems, the treatment of choice of infections with ESBL-producers. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut–immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome—and especially Clostridium difficile infection (currently the only used as clinical treatment)—recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases. [ABSTRACT FROM AUTHOR]

The lower female reproductive tract is notoriously dominated by Lactobacillus species, among which Lactobacillus crispatus emerges for its protective and health‐promoting activities. Although previous comparative genome analyses highlighted genetic and phenotypic diversity within the L. crispatus species, most studies have focused on the presence/absence of accessory genes. Here, we investigated the variation at the single nucleotide level within protein‐encoding genes shared across a human‐derived L. crispatus strain selection, which includes 200 currently available human‐derived L. crispatus genomes as well as 41 chromosome sequences of such taxon that have been decoded in the framework of this study. Such data clearly pointed out the presence of intra‐species micro‐diversities that could have evolutionary significance contributing to phenotypical diversification by affecting protein domains. Specifically, two single nucleotide variations in the type II pullulanase gene sequence led to specific amino acid substitutions, possibly explaining the substantial differences in the growth performances and competition abilities observed in a multi‐strain bioreactor culture simulating the vaginal environment. Accordingly, L. crispatus strains display different growth performances, suggesting that the colonisation and stable persistence in the female reproductive tract between the members of this taxon is highly variable. [ABSTRACT FROM AUTHOR]

We do not seem to be the only owner of our body; it houses a large population of microorganisms. Through countless years of coevolution, microbes and hosts have developed complex relationships. In the past few years, the impact of microbial communities on their host has received significant attention. Advanced molecular sequencing techniques have revealed a remarkable diversity of the organ-specific microbiota populations, including in the reproductive tract. Currently, the goal of researchers has shifted to generate and perceive the molecular data of those hidden travelers of our body and harness them for the betterment of human health. Recently, microbial communities of the lower and upper reproductive tract and their correlation with the implication in reproductive health and disease have been extensively studied. Many intrinsic and extrinsic factors influences the female reproductive tract microbiota (FRTM) that directly affects the reproductive health. It is now believed that FRTM dominated by Lactobacilli may play an essential role in obstetric health beyond the woman's intimate comfort and well-being. Women with altered microbiota may face numerous health-related issues. Altered microbiota can be manipulated and restored to their original shape to re-establish normal reproductive health. The aim of the present review is to summarize the FRTM functional aspects that influence reproductive health. [ABSTRACT FROM AUTHOR]

Purpose of Review: Exposure to bioaerosols at dairies has long been associated with allergy, respiratory disease, and decreases in lung function. Recent advancements in exposure assessments have aided our understanding on the size distribution and composition of these bioaerosols, but investigations focusing solely on exposures may overlook important intrinsic factors impacting worker's susceptibility to disease. Recent Findings: In our review, we discuss the most recent studies examining the exposures and genetic factors that contribute to occupational disease in dairy work. We also review more recent concerns in livestock work associated with zoonotic pathogens, antimicrobial resistant genes, and the role of the human microbiome. Summary: The studies highlighted in this review demonstrate the need for further research to better understand bioaerosol exposure–response relationships in the context of extrinsic and intrinsic factors, antibiotic-resistant genes, viral pathogens, and the human microbiome to help inform effective interventions that improve respiratory health among dairy farmers. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is a common cause of vaginitis worldwide and is associated with serious reproductive health outcomes, including increased risk of preterm birth, sexually transmitted infections, and pelvic inflammatory disease. The current and only FDA-approved treatment regimens for BV are antibiotics, such as metronidazole and clindamycin. Antibiotics provide a short-term cure for bacterial vaginosis; however, fail to provide a consistent long-term cure for many women. Fifty to eighty percent of women experience a BV recurrence within a year of completing antibiotic treatment. This may be because after antibiotic treatment, beneficial strains of Lactobacillus, such as L. crispatus, do not recolonize the vagina. In the absence of an effective long-term cure, patients, providers, and researchers are exploring different approaches to treatment and prevention, resulting in a rapid evolution of perspectives on BV pathogenesis and approaches to management. Current areas of investigation for BV management include probiotics, vaginal microbiome transplantation, pH modulation, and biofilm disruption. Behavioral modifications that may help include smoking cessation, condom use and hormonal contraception. Additional strategies considered by many people include dietary modification, non-medical vaginally applied products, choice of lubricant, and treatments from medical practices outside of allopathic medicine. This review aims to provide a comprehensive and up to date outline of the landscape of ongoing and potential treatment and prevention strategies for BV. [ABSTRACT FROM AUTHOR]

Female reproductive health is strongly associated with healthy vaginal microbiota, which is thought to be ensured by the dominance of certain Lactobacillus species. Lactobacilli control the vaginal microenvironment through several factors and mechanisms. One of them is their ability to produce hydrogen peroxide (H2O2). The role of Lactobacillus-derived H2O2 in the vaginal microbial community has been intensively investigated in several studies with many designs. However, results and data are controversial and challenging to interpret in vivo. Defining the underlying mechanisms responsible for a physiological vaginal ecosystem is crucial since it could directly affect probiotic treatment attempts. This review aims to summarize current knowledge on the topic, focusing on probiotic treatment possibilities. [ABSTRACT FROM AUTHOR]

Titanium mesh (Ti‐mesh) for guided bone regeneration (GBR) approaches has been extensively considered to offer space maintenance in reconstructing the alveolar ridge within bone defects due to its superb mechanical properties and biocompatibility. However, soft tissue invasion across the pores of the Ti‐mesh and intrinsically limited bioactivity of the titanium substrates often hinder satisfactory clinical outcomes in GBR treatments. Here, a cell recognitive osteogenic barrier coating was proposed using a bioengineered mussel adhesive protein (MAP) fused with Alg–Gly–Asp (RGD) peptide to achieve highly accelerated bone regeneration. The fusion bioadhesive MAP‐RGD exhibited outstanding performance as a bioactive physical barrier that enabled effective cell occlusion and a prolonged, localized delivery of bone morphogenetic protein‐2 (BMP‐2). The MAP‐RGD@BMP‐2 coating promoted in vitro cellular behaviors and osteogenic commitments of mesenchymal stem cells (MSCs) via the synergistic crosstalk effects of the RGD peptide and BMP‐2 in a surface‐bound manner. The facile gluing of MAP‐RGD@BMP‐2 onto the Ti‐mesh led to a distinguishable acceleration of the in vivo formation of new bone in terms of quantity and maturity in a rat calvarial defect. Hence, our protein‐based cell recognitive osteogenic barrier coating can be an excellent therapeutic platform to improve the clinical predictability of GBR treatment. [ABSTRACT FROM AUTHOR]

Resistance to carbapenems in Enterobacterales has become a matter of the highest concern in the last decade. Recently, Enterobacterales harboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a serious therapeutic challenge for clinicians. In this study, we analyzed eight Klebsiella pneumoniae and two Enterobacter cloacae complex isolates with multiple carbapenemases, with regard to antibiotic susceptibility, β-lactamase production and plasmid content. The isolates demonstrated uniform resistance to amoxicillin/clavulanate, piperacillin/tazobactam, cefuroxime, ceftazidime, cefotaxime, ceftriaxone and ertapenem. Among novel β-lactam/inhibitor combinations, ceftazidime/avibactam exhibited moderate activity, with 50% of isolates susceptible. All isolates demonstrated resistance to imipenem/cilastatin/relebactam, and all but one to ceftolozane/tazobactam. Four isolates exhibited a multidrug-resistant phenotype (MDR), whereas six were allocated to an extensively drug-resistant phenotype (XDR). OKNV detected three combinations of carbapenemases: OXA-48+NDM (five isolates), OXA-48+VIM (three isolates) and OXA-48+KPC (two isolates). Inter-array testing identified a wide variety of resistance genes for β-lactam antibiotics: blaCTX-M-15, blaTEM, blaSHV, blaOXA-1, blaOXA-2, blaOXA-9, aminoglycosides: aac6, aad, rmt, arm and aph, fluoroquinolones: qnrA, qnrB and qnrS, sulphonamides: sul1 and sul2 and trimethoprim: dfrA5, dfrA7, dfrA14, dfrA17 and dfrA19. mcr genes were reported for the first time in Croatia. This study demonstrated the ability of K. pneumoniae and E. cloacae to acquire various resistance determinants under the selection pressure of antibiotics widely used during the COVID-19 pandemic. The novel inter-array method showed good correlation with OKNV and PCR, although some discrepancies were found. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine the prevalence of Escherichia coli in shrimps and mussels, and to determine the distribution of β-lactam, aminoglycoside, quinolone, and multi-drug resistance phenotypically and genotypically in E. coli isolates obtained from mussels and shrimps in Istanbul. Faecal samples were collected from mussels (n = 96) and shrimps (n = 96) from the Marmara Sea coastline and fish markets in Istanbul. For the detection of antibiotic susceptibilities, seven antibiotic groups were used. β-lactamase, aminoglycoside, and quinolone genes were also determined. A total of 34 (17.7%, 15 shrimps, and 19 mussels) E. coli were isolated, and 17 (50%) were found to be resistant to one or more antimicrobials. The highest resistance was seen against aminoglycosides with 11 isolates (32.35%), followed by quinolones with 10 isolates (29.41%) and extended-spectrum β-lactamase (ESBL) with 4 isolates (11.76%). Multi-drug resistance was detected in 5 isolates (14.7%) from 3 shrimp and 2 mussel samples. The prevalence of ESBL genes was demonstrated at 3.84% in mussels and shrimp samples. There were no AmpC and carbapenemase-producing genes. These samples harbored blaCTX-M-1 (n = 3) and blaTEM (n = 4). Ten isolates were resistant to aminoglycosides genotypically. Resistance genes detected were strB in 2 isolates, aadA in 5, strB and aadA together in 3, ANT(')-Ia, aphA1 and aphA2 simultaneously in 3, aphA1 in 1, aac(3)- IIa in 1 isolate. aac(6')-Ib-cr gene was detected in only one of 10 phenotypically resistant isolates to quinolones. [ABSTRACT FROM AUTHOR]

Acacia arabica commonly known as 'babul' has been widely used for the treatment of numerous diseases, including diabetes due to their potential pharmacological actions. The aim of the present study was to investigate the insulinotropic and antidiabetic properties of ethanol extract of Acacia arabica (EEAA) bark through in vitro and in vivo studies in high fat-fed (HFF) rats. EEAA at 40-5000 µg/ml significantly increased (P<0.05-0.001) insulin secretion with 5.6 and 16.7 mM glucose, respectively, from clonal pancreatic BRIN BD11 ß-cells. Similarly, EEAA at 10-40 µg/ml demonstrated a substantial (P<0.05-0.001) insulin secretory effect with 16.7 mM glucose from isolated mouse islets, with a magnitude comparable to 1 µM glucagon-like peptide-1 (GLP-1). Diazoxide, verapamil, and calcium-free conditions decreased insulin secretion by 25-26%. The insulin secretory effect was further potentiated (P<0.05-0.01) with 200 µM isobutylmethylxanthine (IBMX; 1.5-fold), 200 µM tolbutamide (1.4-fold), and 30 mM KCl (1.4-fold). EEAA at 40 µg/ml, induced membrane depolarization and elevated intracellular Ca2+ as well as increased (P<0.05-0.001) glucose uptake in 3T3L1 cells and inhibited starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity, and protein glycation by 15-38%, 11-29%, 15-64%, and 21-38% (P<0.05, 0.001), respectively. In HFF rats, EEAA (250 mg/5 ml/kg) improved glucose tolerance, plasma insulin, and GLP-1 levels, and lowered DPP-IV enzyme activity. Phytochemical screening of EEAA revealed the presence of flavonoids, tannins and anthraquinone. These naturally occurring phytoconstituents may contribute to the potential antidiabetic actions of EEAA. Thus, our finding suggests that EEAA, as a good source of antidiabetic constituents, would be beneficial for Type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

In this study, Lactobacillus crispatus UBLCp01, Lactobacillus gasseri UBLG36, and Lactobacillus johnsonii UBLJ01 isolated from the vagina of healthy reproductive age Indian women were screened for beneficial probiotic properties. These strains showed the ability to survive acidic and simulated vaginal fluid conditions and could adhere to mucin. Lact. gasseri UBLG36, and Lact. johnsonii UBLJ01 produced d- and l-lactic acid, whereas Lact. crispatus UBLCp01 produced hydrogen peroxide and d- and l-lactic acid. All strains inhibited the growth of pathogens (Escherichia coli, Gardnerella vaginalis, Proteus mirabilis, and Candida albicans) and were capable of co-aggregating with them with varying degrees. Strains secreted exopolysaccharides and formed biofilms under in vitro conditions. Safety assessment showed that these strains had a usual antibiotic susceptibility profile, did not produce hemolysins, gelatinases, and mucin degrading enzymes. Based on strain characteristics and beneficial properties, we believe that these strains are promising candidates for human trials to confirm their ability to prevent/treat vaginal dysbiosis and maintain a healthy vaginal eco-system. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the inflammatory reaction and the ability to induce mineralization activity of a new repair material, NeoPUTTY (NPutty; NuSmile, USA), in comparison with Bio-C Repair (BC; Angelus, Brazil) and MTA Repair HP (MTA HP; Angelus, Brazil)., Methodology: Polyethylene tubes were filled with materials or kept empty (control group, CG) and implanted in subcutaneous tissue of rats for 7, 15, 30, and 60 days (n = 6/group). Capsule thickness, number of inflammatory cells (ICs), fibroblasts, collagen content, and von Kossa analysis were performed. Unstained sections were evaluated under polarized light and by immunohistochemistry for osteocalcin (OCN). Data were submitted to two-way anova followed by Tukey's test (p ≤ .05), except for OCN. OCN data were submitted to Kruskal-Wallis and Dunn and Friedman post hoc tests followed by the Nemenyi test at a significance level of 5%., Results: At 7, 15, and 30 days, thick capsules containing numerous ICs were seen around the materials. At 60 days, a moderate inflammatory reaction was observed for NPutty, BC while MTA HP presented thin capsules with moderate inflammatory cells. In all periods, NPutty specimens contained the highest values of ICs (p < .05). From 7 to 60 days, the number of ICs reduced significantly while an increase in the number of fibroblasts and birefringent collagen content was observed. At 7 and 15 days, no significant difference was observed in the immunoexpression of OCN (p > .05). At 30 and 60 days, NPutty showed the lowest values of OCN (p < .05). At 60 days, a similar immunoexpression was observed for BC and MTA HP (p > .05). In all time intervals, capsules around NPutty, BC, and MTA HP showed von Kossa-positive and birefringent structures., Conclusions: Despite the greater inflammatory reaction promoted by NeoPutty than BC and MTA HP, the reduction in the thickness of capsules, the increase in the number of fibroblasts, and the reduction in the number of ICs indicate that this bioceramic material is biocompatible Furthermore, NeoPutty presents the ability to induce mineralization activity., (© 2024 British Endodontic Society. Published by John Wiley & Sons Ltd.)

The vagina endures multifaceted changes from neonatal to menopausal phases due to hormonal flux, metabolite deposition, and microbial colonization. These features have important implications in women's health. Several pre-factors show dynamic characteristics according to the phases that shift the vaginal microbiota from anaerobes to aerobes which is a hallmark of healthy vaginal environment. These factors include oestrogen levels, glycogen deposition, and vaginal microstructure. In the adult phase, Lactobacillus is highly dominant and regulates pH, adherence, aggregation, immune modulation, synthesis of bacteriocins, and biosurfactants (BSs) which are antagonistic to pathogens. Maternal factors are protective by favouring the colonization of lactobacilli in the vagina in the neonatal phase, which diminishes with age. The dominance of lactobacilli and dysbiosis in the adult phase depends on intrinsic and extrinsic factors in women, which vary between ethnicities. Recent developments in probiotics used against vaginal microbiome dysbiosis have shown great promise in restoring the normal microbiota including preventing the loss of beneficial bacteria. However, further in-depth studies are warranted to ensure long-term protection by probiotics. This review highlights various aspects of the vaginal microenvironment in different phases of growth and diverse ethnicities. Furthermore, it discusses future trends for formulating more effective population-specific probiotics and implications of paraprobiotics and postbiotics as effective therapeutics. [ABSTRACT FROM AUTHOR]

Background: Extended-spectrum β lactamases (ESBLs), have the ability to hydrolyze and cause resistance to various types of the β-lactam antibiotics, including the extended-spectrum (or third-generation) cephalosporins (e.g., cefotaxime, ceftriaxone, ceftazidime) and monobactams (e.g., aztreonam). ESBL-producing Gram negative bacteria is still posing significant therapeutic challenges. Objectives: To assess the prevalence and molecular characteristics of ESBL producing Gram negative bacilli, isolated from a cohort of pediatric patients in Gaza hospitals. Methods: A total of 322 isolates of Gram-negative bacilli were collected from four referral pediatric hospitals in Gaza, namely: Al-Nasr, Al-Rantisi, Al-Durra and Beit Hanoun hospitals. These isolates were tested for ESBL production using the double disk synergy and CHROMagar phenotypic methods. Molecular characterization of the ESBL producing strains was performed using PCR targeting the CTX-M, TEM and SHV genes. Antibiotic profile was done using Kirby Bauer method according to Clinical and Laboratory Standard Institute. Results: Out of 322 isolates tested by phenotypic methods, 166 (51.6%) were ESBL positive. The prevalence of ESBL production in Al-Nasr, Al-Rantisi, Al-Durra and Beit Hanoun hospitals was 54%, 52.5%, 45.5% and 52.8% respectively. The prevalence of ESBL production among Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp., Proteus mirabilis, Enterobacter spp., Citrobacter spp., and Serratia marcescens is 55.3%, 63.4%, 17.8%, 57.1%, 33.3%, 28.5%, 38.4%, and 4% respectively. ESBL production among urine, pus, blood, CSF and sputum was 53.3%, 55.2%, 47.4%, 33.3%, and 25% respectively. Out of the 322 isolates, 144 were screened for CTX-M, TEM and SHV production. Using PCR, 85 (59%) had at least one gene. The prevalence rate of CTX-M, TEM and SHV genes was 60%, 57.6%, and 38.3% respectively. Meropenem and amikacin were highest rates of susceptibility antibiotics against ESBLs producers (83.1% and 82.5% respectively), while the least effective antibiotics were amoxicillin (3.1%) and cephalexin (13.9%). Moreover, ESBLs producers showed high resistance rate to cefotaxime, ceftriaxone and ceftazidime (79.5%, 78.9% and 79.5% respectively). Conclusion: Our results show high prevalence of ESBL production among Gram negative bacilli isolated from children in different pediatric hospitals in Gaza strip. A substantial level of resistance to first and second generation cephalosporins was also observed. This ascertains the need for a rational antibiotic prescription and consumption policy. [ABSTRACT FROM AUTHOR]

To evaluate the characteristics and synthesis activity of osteoblasts extracted from the calvaria of offspring of rats exposed to maternal hyperthyroidism. Twelve adult Wistar rats were divided into two groups, one control and one treated with daily administration of L-thyroxine by an orogastric tube (50 µg/animal/day) during pregnancy. Three days after delivery and confirmation of the mothers' hyperthyroidism, the offspring were euthanized for the extraction of osteoblasts from the calvaria. At 7, 14, and 21 days, proliferation activity was assessed using MTT assay, while alkaline phosphatase (ALP) activity was assessed by the BCIP/NBT method. At 21 days, the total area of the mineralized matrix stained by von Kossa was evaluated by morphometry. The expression of gene transcripts for Runx2, Bmp2, Fgfr1, collagen type 1 (Col1), osteocalcin (Oc), and osteopontin (Op) were evaluated by real-time RT-PCR. Means were compared using the Student's t-test. FA activity was significantly higher at 14 and 21 days in cultures of osteoblasts extracted from offspring exposed to maternal hyperthyroidism, while MTT conversion was significantly lower at 21 days in this group. Osteoblast cultures of neonates exposed to maternal hyperthyroidism also showed a larger total area of mineralized matrix and greater expression of gene transcripts for Oc and Op. Maternal hyperthyroidism increases the activity of matrix synthesis, alkaline phosphatase activity, and expression of gene transcripts for osteocalcin and osteopontin in the osteoblasts, extracted from the calvaria of the offspring, which may be one of the mechanisms of premature fusion of cranial sutures. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4–6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota. [ABSTRACT FROM AUTHOR]

During November to December 2020, a high rate of COVID-19-associated pneumonia with bacterial superinfections due to multidrug-resistant (MDR) pathogens was recorded in a COVID-19 hospital in Zagreb. This study analyzed the causative agents of bacterial superinfections among patients with serious forms of COVID-19. In total, 118 patients were hospitalized in the intensive care unit (ICU) of the COVID-19 hospital. Forty-six out of 118 patients (39%) developed serious bacterial infection (VAP or BSI or both) during their stay in ICU. The total mortality rate was 83/118 (70%). The mortality rate due to bacterial infection or a combination of ARDS with bacterial superinfection was 33% (40/118). Six patients had MDR organisms and 34 had XDR (extensively drug-resistant). The dominant species was Acinetobacter baumannii with all isolates (34) being carbapenem-resistant (CRAB) and positive for carbapenem-hydrolyzing oxacillinases (CHDL). One Escherichia coli causing pneumonia harboured the blaCTX-M-15 gene. It appears that the dominant resistance determinants of causative agents depend on the local epidemiology in the particular COVID center. Acinetobacter baumannii seems to easily spread in overcrowded ICUs. Croatia belongs to the 15 countries in the world with the highest mortality rate among COVID-19 patients, which could be in part attributable to the high prevalence of bacterial infections in local ICUs. [ABSTRACT FROM AUTHOR]

The consumption and composition of food in daily life predict our health in long run. The relation of diabetes to sweets is quite popular. Diabetes hampers the glucose and insulin regulation in the human body by damaging pancreatic β cells. Diabetes has a strong potential towards altering cellular mechanisms of organs causing unlawful performance. Diabetes alters pathways like TLR4, AChE, NF‐ĸB, LPL, and PPAR at different sites that affect the normal cellular machinery and cause damage to the local tissue and organ. The long‐lasting effect of diabetes was observed in vascular, cardia, nervous, skeletal, reproductive, hepatic, ocular, and renal systems. The increasing awareness of diabetes and its concern has awakened the common people more enthusiastically. Due to rising harm from diabetes, scientific researchers tend to have more eyes toward it. While searching for diabetes solutions, fenugreek diosgenin could pop up with some positive effects in curing the same. Diosgenin helps to lower the scathe of diabetes by modifying cellular pathways in favor of healthy bodily functions. Diosgenin altered the pathways for renewal of pancreatic β cells for better insulin secretion, initiate GLUT4, enhanced DHEA, modify ER‐α‐mediated PI3K/Akt pathways. Diosgenin can be an appropriate insult for diabetes in a much evolving way for a healthy lifestyle. Practical applications: Diabetes is one of the most death causing diseases in the medical world. Regrettably the cure of diabetes is yet to be found. Various scientific team working on the same to look after the most appropriate way for diabetes treatment. There is enormous growth of nutraceutical in the market claiming for cure of different metabolic disorders. Among various bioactive compound fenugreek's diosgenin could took a leap over other in curing and preventing the damage caused by diabetes to different organs. The role of diosgenin in curing various metabolic disorders is quite popular from some time. This article also emphasizes over beneficiary effect of diosgenin in curing the damages caused by diabetes by altering cellular metabolism processes. Hence diosgenin could be a better way for researchers to develop a method for diabetes treatment. [ABSTRACT FROM AUTHOR]

K. pneumoniae isolates often harbor various antibiotic resistance determinants including extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases (p-Amp-C) and carbapenemases. In this study we analyzed 65 K. pneumoniae isolates obtained from urinary tract infections in the outpatients setting, with regard to antibiotic susceptibility, β-lactamase production, virulence traits and plasmid content. Antibiotic susceptibility was determined by broth microdilution method. PCR was applied to detect genes encoding ESBLs, p-Amp-C and carbapenemases and plasmid incompatibility groups. Phenotypic methods were applied to characterize virulence determinants. Increasing resistance trend was observed for amoxicillin/clavulanate, imipenem, meropenem and ciprofloxacin. The study showed that ESBLs belonging to the CTX-M family, conferring high level of resistance to expanded-spectrum cephalosporins (ESC) were the dominant resistance trait among early isolates (2013 to 2016) whereas OXA-48 carbapenemase, belonging to class D, emerged in significant numbers after 2017. OXA-48 producing organisms coharbored ESBLs. KPC-2 was dominant among isolates from Dubrovnik in the recent years. Colistin resistance was reported in three isolates. Inc L/M was the dominant plasmid in the later period, encoding OXA-48. Hyperviscosity was linked to KPC positivity and emerged in the later period. This report describes evolution of antibiotic resistance in K. pneumoniae from ESBLs to carbapenemases and colistin resistance. The study demonstrated the ability of K. pneumoniae to acquire various resistance determinants, over time. The striking diversity of the UTI isolates could result from introduction of the isolates from the hospitals, transfer of plasmids and multidirectional evolution. [ABSTRACT FROM AUTHOR]

The natural environment is a primary source of infections caused by members of Burkholderia cepacia complex (BCC), but the release of human waste may in return enrich the natural environment with clinically relevant BCC. Seven BCC isolates from environment influenced by human liquid or solid waste across Croatia, and one clinical isolate was characterised. B. multivorans recovered from the soil at illegal dumpsite belonged to sequence type (ST)19; B. ambifaria from the agricultural soil fertilized with swine or poultry manure to ST927 or new ST; B. cenocepacia from creek sediment, river water and wound swab to new STs. Antimicrobial susceptibility of isolates ranged from sensitive to multidrug-resistant. A variety of blaTEM genes was confirmed in isolates. Isolates expressed the virulence factors and survived in river water during 50 days. The BCC present natural environments influenced by the human waste are of clinical relevance and a potential source of sporadic infections. [ABSTRACT FROM AUTHOR]

The probiotics market is one of the fastest growing segments of the food industry as there is growing scientific evidence of the positive health effects of probiotics on consumers. Currently, there are various forms of probiotic products and they can be categorized according to dosage form and the site of action. To increase the effectiveness of probiotic preparations, they need to be specifically designed so they can target different sites, such as the oral, upper respiratory or gastrointestinal tracts. Here we review the characteristics of different dosage forms of probiotics and discuss methods to improve their bioavailability in detail, in the hope that this article will provide a reference for the development of probiotic products. [ABSTRACT FROM AUTHOR]

The human microbiome has been given increasing importance in recent years. The establishment of sequencing-based technology has made it possible to identify a large number of bacterial species that were previously beyond the scope of culture-based technologies. Just as microbiome diagnostics has emerged as a major point of focus in science, reproductive medicine has developed into a subject of avid interest, particularly with regard to causal research and treatment options for implantation failure. Thus, the vaginal microbiome is discussed as a factor influencing infertility and a promising target for treatment options. The present review provides an overview of current research concerning the impact of the vaginal microbiome on the outcome of reproductive measures. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis, possibly even bacterial vaginosis. This imbalance has a negative impact on implantation rates in assisted reproductive technologies and may also be responsible for habitual abortions. Screening of the microbiome in conjunction with antibiotic and/or probiotic treatment appears to be one way of improving pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Recently, a dramatic increase of Klebsiella pneumoniae positive for OXA-48 β-lactamases was observed first in the hospital setting and later in the long-term care facilities (LTCFs) and community in the Zagreb County, particularly, in urinary isolates. The aim of the study was to analyse the epidemiology and the mechanisms of antibiotic resistance of OXA-48 carbapenemase producing K. pneumoniae strains isolated from urine of non-hospitalized elderly patients. Results: The isolates were classified into two groups: one originated from the LTCFs and the other from the community. Extended-spectrum β-lactamases (ESBLs) were detected by double disk-synergy (DDST) and combined disk tests in 55% of the isolates (51/92). The ESBL-positive isolates exhibited resistance to expanded-spectrum cephalosporins (ESC) and in majority of cases to gentamicin. LTCFs isolates showed a significantly lower rate of additional ESBLs and consequential resistance to ESC and a lower gentamicin resistance rate compared to the community isolates, similarly to hospital isolates in Zagreb, pointing out to the possible transmission from hospitals.ESBL production was associated with group 1 of CTX-M or SHV-12 β-lactamases. Ertapenem resistance was transferable from only 12 isolates. blaOXA-48 genes were carried by IncL plasmid in 42 isolates. In addition IncFII and IncFIB were identified in 18 and 2 isolates, respectively. Two new sequence types were reported: ST4870 and ST4781. Conclusions: This study showed eruptive and extensive diffusion of OXA-48 carbapenemase to LTCFs and community population in Zagreb County, particularly affecting patients with UTIs and urinary catheters. On the basis of susceptibility testing, β-lactamase production, conjugation experiments, MLST and plasmid characterization it can be concluded that there was horizontal gene transfer between unrelated isolates, responsible for epidemic spread of OXA-48 carbapenemase in the LTCFs and the community The rapid spread of OXA-48 producing K. pneumoniae points out to the shortcomings in the infection control measures. [ABSTRACT FROM AUTHOR]

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