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HIV infection is responsible for one the most devastating human pandemics. The advent of antiretroviral therapy has changed the course of the pandemic and saved millions of lives. Complex therapeutic regimens have been introduced since 1996 and have contributed to the transformation of HIV infection into a treatable chronic diseases. New types of potent antiretrovirals and their combinations, including \"once daily\" treatment, have simplified the regimens and diminished side effects. Nevertheless the adherence to antiretroviral therapy remains unsatisfactory and varies between 27 and 80% across different population in various studies, compared with the required level of 95%. The lack of adherence to antiretroviral therapy is a multi-factorial and dynamic process which raises considerable difficulties for long-term follow-up. Current solutions to this problem are complex. These should be applied by a multidisciplinary team and should take into account key features related to both the individual and social factors as well as to the population to whom it belongs (children, teenagers, elderly, marginalized population like drug users, incarcerated patients, sex workers, etc.). Importantly, adherence should continue to be monitored even in patients known to be compliant. In case of subsequent failure the team should identify the reasons for non-adherence and apply the appropriate methods. Where usual methods have no chance of success, a coordinated package of services also known as \"harm reduction\" can be offered in order to reduce the risks of transmission. The current article analyses the concept of adherence to antiretroviral therapy, the shortcomings of this medication and the methods that can be applied in practice to increase adherence. Emphasis is placed on the analysis of groups at high risk for HIV infection that currently represent the spearhead with which the HIV pandemic is spreading.

SARS-CoV-2 is the most recent coronavirus which crossed the species barrier in 2019 and provoked a still ongoing and dangerous pandemic known as coronavirus disease 2019 (COVID-19). The SARS-CoV-2 infection has triggered an impressive amount of clinical and experimental studies to identify an effective and safe therapy to stop the pandemic spread. Hence, numerous trials and studies have scrutinized the analogies between SARS-CoV-2 and other corona viruses or the host-virus interactions and their similarities with immune system disorders. Still, the pathogenic mechanisms behind SARS-CoV-2 have been partially deciphered and the current therapies have not yet met the initial enthusiastic expectations. So far COVID-19 therapies have targeted various pathogenic mechanisms, namely the neutralization of ACE2 receptors or SARS-CoV-2 spike protein epitopes, the disruption of the endocytic pathways using hydroxychloroquine, arbidol, or anti-Janus kinase inhibitors, the inhibition of RNA-dependent RNA polymerase using nucleotide analogues such as remdesivir, immunosuppressive drugs or molecules acting on the immune response (corticoids, interferons, monoclonal antibodies against inflammatory cytokines, mesenchymal stem cells) and convalescent plasma administration together with numerous drugs with unproven effect against SARS-CoV-2 but with potential antiviral activities (antiretrovirals, antimalarial drugs, antibiotics, etc.). Nevertheless, these therapies have been associated with side effects and contradictory results. At the same time a specific SARS-CoV-2 vaccine is a long-term solution requiring clinical validation and important investments together with appropriate strategies to promote the confidence in the safety of the new vaccine. The article revises the current state of SARS-CoV-2 therapeutic options but advises towards a more cautious and individualized treatment approach centred on the clinical features, immune particularities, and the risk-benefit balance.

Cancer is a leading cause of death globally, claiming millions of lives each year. Despite the availability of numerous anticancer drugs, the need for new treatment options remains essential. Many current therapies come with significant toxicity, lead to various side effects, or do not consistently deliver the expected therapeutic results. Purines and pyrimidines are fundamental building blocks of nucleic acids and play crucial roles in cellular metabolism and signaling. Recent advances in medicinal chemistry have led to the development and synthesis of various derivatives that exhibit selective cytotoxic effects against cancer cells while minimizing toxicity to healthy tissues. Purine and pyrimidine scaffolds, due to their well-established biological roles and structural versatility, have emerged as key pharmacophoric fragments in anticancer drug discovery. In recent years, the rational design of hybrid molecules incorporating these heterocycles has shown promise in overcoming drug resistance, improving target selectivity, and enhancing pharmacological profiles. Purine and pyrimidines scaffolds hold significant potential as foundations for novel antitumor drugs, with established representatives in cancer treatment, including 5-fluorouracil, cladribine, capecitabine, and several others. In addition, the article discusses the challenges and future developments of purine and pyrimidine derivatives and hybrid molecules as antitumor drugs and emphasizes the need for continued research to optimize their effectiveness and reduce side effects. Overall, the innovative use of these compounds represents a major advance in targeted cancer therapy and holds promise for improving the therapeutic efficacy of malignant diseases.

Background/Objectives: In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with Salvia officinalis extract, compared to metformin as a standard therapeutic agent. Methods: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. Results: The combination of the synthetic sulfonamide (S) with Salvia officinalis extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (p < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (p > 0.05). Conclusions: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as Salvia officinalis to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and Salvia officinalis extract in a diabetic animal model.

Background/Objectives: Sustained drug exposure is a key factor in the treatment of patients infected with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) in order to achieve the intended virological response. Although influenced also by other parameters, adherence to the treatment scheme is the most important for adequate drug exposure. This can be assessed by therapeutic drug monitoring (TDM). Tenofovir (TFV) is a nucleotide analogue used in the treatment of both HIV and HBV. Although various analytical methods for the quantification of tenofovir prodrugs have been published, there is limited literature on methods for simultaneous TFV and its active metabolite, tenofovir diphosphate (TFVDP) direct determination. Methods: In this study, we describe a novel micro-liquid-chromatography-mass spectrometry (micro-LC-MS/MS) method for TDM of TFV and TFVDP in biological matrices (whole blood, plasma). The challenging separation of the high-polarity analytes was resolved on an amino stationary phase, eluted in HILIC (hydrophilic interaction liquid chromatography) mode. The sample preparation included a clean-up step with hexane for the removal of lipophilic compounds and then protein precipitation with organic solvent. Results: The achieved low limits of quantification in blood were 0.25 ng/mL for TFV, and 0.5 ng/mL for TFVDP. Linearity, accuracy (91.63–109.18%), precision (2.48–14.08), and stability were validated for whole blood matrix, meeting the guidelines performance criteria. Samples collected from treated patients were analyzed, with results being in accordance with the reported pharmacokinetics. Conclusions: The new method is adequate for analyzing samples in a clinical set-up. The measurement of both TFV and TFVDP improves clinical decision by an in-depth evaluation of long-term adherence, and together with viral load and resistance data helps guiding the treatment towards the intended virological suppression.

Objectives: The objective of this study was to evaluate changes in anatomical point position, cranio-cervical posture, and respiratory dimensions following conventional bimaxillary total prosthetic rehabilitation. Methods: A prospective, longitudinal, observational, analytical study was conducted on 12 patients, aged 55 to 75 years, at the Department of Dental Prosthetics at the University of Medicine and Pharmacy in Cluj-Napoca. All patients had complete bimaxillary edentulism and received removable dentures as treatment. Clinical and cephalometric analyses were performed before and after prosthetic treatment to compare changes. The cephalometric analysis was based on the guidelines of Tweed and Rocabado for evaluation. Quantitative data were described using the mean and standard deviation for normal distribution and represented by bar graphs with error bars. A paired samples t-test was used to determine differences between groups, with a significance threshold of 0.05 for the bilateral p-value. Results: When analyzing changes in cranial base inclination, the corresponding angles exhibited an increase, indicating cephalic extension. A statistically significant difference in the anteroposterior diameter of the oropharyngeal lumen with and without bimaxillary complete dentures was identified (p < 0.05). For hyperdivergent patients, modifications in the position of anatomical features on cephalometry slightly reduced the VDO and had a slight compensatory effect on skeletal typology. In contrast, for hypodivergent patients, modifications to the position of anatomical landmarks also had a compensatory effect on skeletal typology, increasing the VDO. Conclusion: Changes in the position of anatomical features on cephalometry generally have a compensatory effect on skeletal typology after complete denture placement. Complete prosthetic treatment with removable dentures can significantly influence respiratory function by reducing the oropharyngeal lumen and body posture by cephalic extension and attenuation of the lordotic curvature of the cervical spine.

Background: During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine. Methods and Results: Case 1: A female patient was admitted with a suspicious cervical mass that emerged within one week after the administration of second dose of the BNT162b2 COVID-19 vaccine. Surgical removal followed by pathology assessment of the specimen confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Case 2: A male patient was admitted with multiple ulcerative oral lesions arising on the third day after the initial dose of the BNT162b2 COVID-19 vaccine. These lesions had a progressive character and during the following months were complicated with repetitive episodes of heavy oral bleeding, requiring blood transfusions. The incisional biopsy of the lesions and pathological assessment of the specimens confirmed the diagnosis of T/NK-cell lymphoma. Conclusions: The safety profile of the mRNA-based vaccines is an undeniable fact. In most cases, suspicions of potentially aggressive side effects were ruled out, proving to be transient post-vaccine reactions. Clinicians should remain alert to report any potentially aggressive manifestations emerging in the context of mRNA COVID-19 vaccination, such as these cases of hematological malignancies, in order to promote additional investigations on the particular mechanisms of action of COVID-19 vaccines and to provide the best medical care to the patients.

Background/Objectives: The marginal adaptation of CAD/CAM restorations remains a key determinant of long-term clinical success, particularly in minimally invasive preparations. This in vitro study evaluated and compared the marginal gap of three CAD/CAM restorative materials—Cerasmart, G-CAM, and IPS Empress CAD—using standardized preparation and SEM measurement protocols. Methods: A total of 18 crowns were fabricated, of which 9 presented margins sufficiently interpretable under SEM and were included in the pooled quantitative analysis (n = 362 measurement points). Marginal gaps were recorded at 45×, 100× and 450× magnification using a Jeol JSM 25S scanning electron microscope. Normality and variance homogeneity were verified prior to parametric testing. Results: When pooled per material group, the mean ± SD marginal gap values were 18.53 ± 14.15 µm for Cerasmart, 21.60 ± 14.89 µm for G-CAM, and 47.09 ± 16.93 µm for IPS Empress CAD. All values fell below the contemporary clinical threshold of <70 µm for adhesive cementation. Pairwise comparison showed a large difference between IPS Empress CAD and the two resin-based materials, whereas the difference between Cerasmart and G-CAM was small. Conclusions: Hybrid and resin nano-ceramic CAD/CAM materials demonstrated narrower marginal gaps compared with the glass ceramic tested, likely due to their lower elastic modulus and greater seating accommodation during cementation. Within the limits of this in vitro design, all materials exhibited marginal adaptation consistent with current clinical acceptability criteria.

Background/Objectives: Edentulism is a significant public health concern, particularly among aging populations, affecting oral functionality, aesthetics, and overall health. This study assessed the edentulism status of patients at the Prosthodontic Clinic of Cluj-Napoca, Romania, and explored the possible correlations with socioeconomic factors such as age, general health, smoking, and alcohol consumption. This study aimed to inform public health strategies to reduce edentulism incidence and improve overall oral health outcomes in Romania. Methods: The current study included 208 patients (127 females and 81 males). Each participant completed a standardized data collection form designed to gather comprehensive information on socio-demographic characteristics (including age, gender, and environmental origin), self-reported general health, and lifestyle habits related to smoking and alcohol consumption. The clinical examination was performed by the same operator, recording the odontal and periodontal status, as well as prosthodontic evaluation (including Kennedy class). Results: Findings indicated that female patients had more frequent class 3 and complete edentulism in the maxilla, while males predominantly presented class 3 in the maxilla and class 1 in the mandible. The age distribution revealed that patients aged 20–40 exhibited the highest prevalence of Kennedy class 3, while those over 60 showed a notable increase in complete edentulism (p < 0.05). Although most patients were from urban areas, no significant difference was found between origin and edentulism class. A significant link between alcoholism and mandibular edentulism was also identified (p < 0.05). Conclusions: Edentulism tends to progress with advancing age, often leading to more extensive tooth loss and the need for comprehensive dental rehabilitation. The condition is closely linked to general health status, highlighting its relevance as a potential indicator of systemic health risks. Lifestyle factors, particularly smoking and alcoholism, appear to contribute significantly to the deterioration of oral health, underscoring the importance of preventive strategies and early intervention.

BackgroundThe risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance.MethodsWe performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time.ResultsDuring a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis.ConclusionsThe study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.