Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age.

Immunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population.

With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019). In total 63,782 pediatric subjects had at least one identified psychotropic prescription. The prevalence of psychotropics use was 5.1-14.6/1,000 pediatric inhabitants. When excluding 42,508 subjects who received only short-time hydroxyzine, the prevalence was 3.1-6.5/1,000 pediatric inhabitants; adolescents and boys had higher exposures. An in-depth analysis of 21,274 subjects accounting for 222,307 psychotropic dispensations, showed antiepileptics as the most frequent psychotropics, consistently with the finding on epilepsy being the most frequent diagnosis; diazepam was the single drug with the highest exposure in almost all ages. 14% of subjects have received at least one medicine with no pediatric information in the labelling, corresponding to 5.5% of dispensed psychotropics. 7.6% of all dispensed psychotropics were used in a non-authorized age range with quetiapine being the most frequent psychotropic as off-label age range; antipsychotics and antidepressants were first as off-label for non-authorized indication. Data from Greece show that a relevant number of patients are prescribed psychotropics, with 1 in 7 being under off-label use. Due to the limitations inherent to pharmacy claims databases, further research using clinical data for a longer follow-up period could confirm and identify trends in psychotropics use in Greece.

Community Antibiotic Consumption in Cyprus for the Period 2015 to 2022.

BACKGROUND: Cyprus currently reports to ESAC-Net the total consumption of antimicrobials, without distinguishing between hospital and community-based antibiotic use. As a result, these data can only provide generalized insights into antimicrobial trends in the country. AIM: This study is a first attempt to retrospectively analyze community antibiotic consumption in Cyprus for the period of 2015 to 2022. MATERIAL AND METHODS: Data on community antimicrobial consumption between 2015 and 2022 were extracted from Pharmatrack's database. Orally administered dispensed antibiotics were categorized under the J01 group of the WHO Anatomical Therapeutic Chemical (ATC) classification and by the WHO's AWaRe classification of antibiotics. Antibiotic consumption was calculated in both packages consumed and per 1000 inhabitants, overall, by year of consumption and districts. RESULTS: During the period of 2015-2022, there was variability in the mean outpatient antibiotic consumption per 1000 inhabitants among the five districts in Cyprus. Community consumption increased by 38% throughout the study period. Additionally, a decrease of 3% in the consumption of WHO 'Access' antibiotics was observed, accompanied with a concurrent increase of 3% in the 'Watch' group. Specifically, in 2022 the WHO 'Access' group consumption in the Cypriot community was 48%, significantly lower than the WHO's goal of 60% and the EU's goal of 70% for 'Access' antibiotic consumption. CONCLUSIONS: Antibiotic consumption in the community of Cyprus between 2015 and 2022 demonstrated substantial variability among districts, with higher consumption in less populated areas. There was an increasing trend in community consumption over the years and a decreasing trend in the percentage of 'Access' antibiotics prescribed.

Is cognitive behavioral therapy more effective than pharmacotherapy for binge spectrum disorders? A systematic review and meta-analysis.

OBJECTIVES: Binge spectrum disorders are prevalent worldwide. Psychiatric and medical comorbidities are common, and societal costs are significant. Evidence-based treatment remains underutilized. Cognitive behavioral therapy is the recommended first-line treatment, but pharmacotherapy may be easier to access. INTERVENTIONS: Meta-analytic evidence directly comparing cognitive behavioral therapy with pharmacotherapy is lacking. We aimed to compare the effects of cognitive behavioral therapy interventions with any pharmacological treatment for binge spectrum disorders. We searched PubMed, Embase, CENTRAL, ClinicalTrials.gov and reference lists for randomized controlled trials comparing cognitive behavioral therapy with any pharmacotherapy for bulimia nervosa/binge eating disorder and performed pairwise meta-analytic evaluations. PRIMARY OUTCOMES: Primary outcomes are remission and frequency of binges. Secondary outcomes are frequency of purges, response, eating disorder psychopathology, weight/body mass index, depression, anxiety, quality of life and dropouts. RESULTS: Eleven randomized controlled trials comparing cognitive behavioral therapy with fluoxetine/imipramine/desipramine/methylphenidate/sibutramine were identified (N = 531). Cognitive behavioral therapy was superior to antidepressants in terms of remission, frequency of binges and eating disorder psychopathology. There were no statistically significant differences for any of the individual cognitive behavioral therapy vs drug comparisons in terms of response/depression/anxiety/weight/quality of life/dropouts. Cognitive behavioral therapy was not superior to sibutramine/methylphenidate for the primary outcomes. CONCLUSIONS: Data are scarce, comparisons underpowered and, considering the inherent methodological limitations of psychotherapy trials, questions arise regarding the presumed superiority of cognitive behavioral therapy. Further research is needed.

Exploring Perceptions and Practices Regarding Adult Vaccination against Seasonal Influenza, Tetanus, Pneumococcal Disease, Herpes Zoster and COVID-19: A Mixed-Methods Study in Greece.

We aimed to document vaccination coverage for five vaccines, predictors of each vaccine's uptake and attitudes regarding adult vaccination. Adults visiting four pharmacies were randomly invited to participate during summer 2022. Among 395 participants (mean age 51.2 years, range 19-96), vaccination rates were 78.1% for influenza and 25.8% for herpes zoster (≥60 years old), 64.3% for pneumococcal disease (≥65 years old), 33.1% for tetanus, while 11.4% had received two and 74.8% ≥3 COVID-19 vaccine doses. Half of participants (50.1%) voiced some degree of hesitancy, and 1.3% were refusers. The strongest predictor of each vaccine's uptake was doctor's recommendation (OR range 11.33-37.66, p < 0.001) and pharmacist's recommendation (4.01-19.52, p < 0.05), except for the COVID-19 vaccine, where the Attitude Towards Adult VACcination (ATAVAC) value of adult vaccination subscale's score was the only predictor (OR: 5.75, p < 0.001). Regarding insufficient coverage, thematic content analysis revealed seven main themes. Insufficient knowledge, the absence of health professionals' recommendation, perception of low susceptibility to disease, negligence and dispute of vaccine effectiveness were universal themes, whereas safety concerns and distrust in authorities were reported solely for COVID-19 vaccination. Designing public interventions aiming to increase trust in adult vaccination is essential in the aftermath of the COVID-19 pandemic. Health professionals' role in recommending strongly adult vaccination is crucial.

Weight gain, gender, and antipsychotics: a disproportionality analysis of the FDA Adverse Event Reporting System database (FAERS).

INTRODUCTION: Side effects are a very important aspect of antipsychotic treatments. Weight gain is an important side effect that jeopardizes the uninterrupted therapy administration, especially in patients with psychiatric conditions. This case-non-case pharmacovigilance study aims at investigating in a real-world adverse event reporting system whether several antipsychotics increase the risk of weight gain reporting, and the differences among men and women as far as weight gain as a reported adverse event is concerned. AREAS COVERED: Adverse event reports submitted to the FDA Adverse Event Reporting System of the Food and Drug Administration of the United States (FAERS) of 24 major antipsychotics were extracted, cleaned, and analyzed to determine which of these drugs were correlated with weight gain. The Reported Odds Ratio (ROR) and the adjusted Reported Odds Ratio (aROR) were calculated for each antipsychotic using logistic regression models. Demographics like age, gender, and concomitant insulin use were taken into consideration for each drug. EXPERT OPINION: Women had a statistically significant increase in weight gain reporting compared to men, while the men's group was associated with a reduced weight gain reporting in every antipsychotics in the logistic regression analyses. Out of the 24 antipsychotics included in our analysis, Aripiprazole, Brexpiprazole, Olanzapine, and Haloperidol had statistically significantly more weight increase reporting compared to the others.

Respiratory Syncytial Virus Vaccines: A Review of the Candidates and the Approved Vaccines.

Respiratory syncytial virus (RSV) is responsible for a significant proportion of global morbidity and mortality affecting young children and older adults. In the aftermath of formalin-inactivated RSV vaccine development, the effort to develop an immunizing agent was carefully guided by epidemiologic and pathophysiological evidence of the virus, including various vaccine technologies. The pipeline of RSV vaccine development includes messenger ribonucleic acid (mRNA), live-attenuated (LAV), subunit, and recombinant vector-based vaccine candidates targeting different virus proteins. The availability of vaccine candidates of various technologies enables adjustment to the individualized needs of each vulnerable age group. Arexvy® (GSK), followed by Abrysvo® (Pfizer), is the first vaccine available for market use as an immunizing agent to prevent lower respiratory tract disease in older adults. Abrysvo is additionally indicated for the passive immunization of infants by maternal administration during pregnancy. This review presents the RSV vaccine pipeline, analyzing the results of clinical trials. The key features of each vaccine technology are also mentioned. Currently, 24 vaccines are in the clinical stage of development, including the 2 licensed vaccines. Research in the field of RSV vaccination, including the pharmacovigilance methods of already approved vaccines, promotes the achievement of successful prevention.

Local Wound Infiltration for Thyroidectomized Patients in the Era of Multimodal Analgesia.

The first few hours following thyroidectomy are the most crucial for pain management. Adequate postoperative pain control, reduction in opioid abuse and the possibility of implementing one-day operations are the considered parameters when developing the postoperative analgesic strategy. A study of the available literature was conducted, exploring the efficacy of (open) thyroidectomy wound infiltration. Seventeen full-text RCTs were extracted. Local anesthetics and non-steroidal anti-inflammatory drugs were infiltrated. Emphasis was given to postoperative pain scores and requirements for rescue analgesia with opioids. Most authors agree that local wound infiltration for thyroidectomized patients is effective in the management of postoperative pain parameters. In the era of multimodal analgesia, thyroidectomy wound infiltration could represent an essential adjunct contributing to lower VAS scores and reduced opioid requirements.

Pharmacotherapy compared to placebo for people with Bulimia Nervosa: A systematic review and meta-analysis.

Bulimia Nervosa is a disorder with high rates of psychiatric and medical comorbidity and substantial societal costs. Cognitive Behavioural Therapy is considered the preferred treatment, but access can be problematic. Pharmacotherapy is more accessible but remains significantly underutilised. We aimed to assess the efficacy, tolerability, and safety of all available forms of pharmacotherapy for the treatment of bulimia nervosa. We conducted a comprehensive search of PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and reference lists of relevant articles up until April 2023. The primary outcomes were remission and binge frequency. 52 randomised controlled trials (RCTs) involving 3313 participants were included in the meta-analysis. Overall, no significant difference was observed between drugs and placebo in terms of remission; however, the available data were limited. Notably, drugs, particularly antidepressants, demonstrated a significant reduction in the frequency of binge episodes compared to placebo. Antidepressants were also found to be more effective than placebo in terms of treatment response and other clinically meaningful outcomes. An important limitation is that few RCTs were available for individual drugs. Our findings provide evidence supporting the increased utilisation of pharmacotherapy in clinical practice and underscore the need for further research involving larger populations and a broader range of outcomes.

Epidemiological Insights on Medication Concurrency and Polypharmacy in People With Multiple Sclerosis in Greece.

BACKGROUND: Besides disease-modifying therapies, various pharmacologic agents are frequently prescribed to people with multiple sclerosis (MS) for symptom treatment and for comorbid conditions. The present study aims to investigate the types and frequencies of agents prescribed to people with MS in Greece using records from the nationwide digital prescription database. METHODS: Prescription records for 21,218 people (65.9% women) with MS were included in the study. The criterion for study inclusion was a minimum of 3 months of continuous prescription of an agent. Identified treatments were further examined by age group. RESULTS: Antispasticity agents (17.5%) and fampridine (14.5%) were the most regularly prescribed symptomatic medications. Antihypertensives (21.1%) and drugs for affective disorders, including antidepressants (36.1%) and anxiolytics (16.2%), were the most frequently prescribed medications for comorbid conditions. Antidepressants were prescribed at almost equally high rates among individuals older than 40 years. Hypertension was one of the leading comorbidities among the study sample, with rates rising significantly after age 40 years and plateauing after age 60 years. Polypharmacy was observed in 22.5% of the study sample, with a higher incidence among people with MS older than 60 years (46.98%). CONCLUSIONS: Agents prescribed for the treatment of disease symptoms and other medical conditions are expected to positively affect quality of life in people with MS. However, polypharmacy seems to be particularly high, especially in the aged population. The potential implications of polypharmacy in the disease course should further be explored.

Clinical, Histological, and Molecular Prognostic Factors in Childhood Medulloblastoma: Where Do We Stand?

Medulloblastomas, highly aggressive neoplasms of the central nervous system (CNS) that present significant heterogeneity in clinical presentation, disease course, and treatment outcomes, are common in childhood. Moreover, patients who survive may be diagnosed with subsequent malignancies during their life or could develop treatment-related medical conditions. Genetic and transcriptomic studies have classified MBs into four subgroups: wingless type (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4, with distinct histological and molecular profiles. However, recent molecular findings resulted in the WHO updating their guidelines and stratifying medulloblastomas into further molecular subgroups, changing the clinical stratification and treatment management. In this review, we discuss most of the histological, clinical, and molecular prognostic factors, as well the feasibility of their application, for better characterization, prognostication, and treatment of medulloblastomas.

Prescribing Z-drugs in Greece: an analysis of the national prescription database from 2018 to 2021.

BACKGROUND: The Z-drugs are indicated for the short-treatment of insomnia, but they are associated with abuse, dependence and side-effects. There are only sparse data about Z-drug prescribing in Greece. METHODS: We analyzed data from the Greek prescription database, considering prescriptions for the available Z-drugs in Greece, i.e., zolpidem and zopiclone, during the period from 01.10.2018 to 01.10.2021 in order to examine the prevalence, monthly number and characteristics of Z-drug prescriptions in Greece. RESULTS: There were 1,229,842 prescriptions for Z-drugs (zolpidem: 89.7%) during the investigated period from 2018 to 2021, which corresponded to 156,554 patients (73.1% ≥ 65 years, 64.5% female). More than half of the patients (65.8%) had more than one prescription with a median number of 8, interquartile range IQR [3, 17], prescriptions during the three-year study period. Most patients (76.1%) were prescribed by medical specialties other than psychiatrists and neurologists, despite a considerable frequency of psychiatric comorbidities (53.7%). About half of patients with anxiety/depression were not prescribed anxiolytics or antidepressants, a practice more frequently observed among medical specialties other than psychiatrists and neurologists. The average annual prevalence of at least one prescription for Z-drugs in the Greek population during 2019-2020 was approximately 0.9% (higher in females and older adults). The monthly number of prescriptions was relatively stable with a median number of 334.2 IQR [310.4; 351.6] prescriptions per 100,000 persons. CONCLUSIONS: A considerable number of patients are prescribed Z-drugs in Greece, more often older adults, females and patients with psychiatric comorbidities. The prescribing physicians were in the majority (70%) internists and general practitioners, while psychiatrists (10.9%) and neurologists (6.1%) accounted for a smaller proportion. Due to the limitations inherent to medical claims databases, further research is warranted in order to elucidate the potential abuse and misuse of Z-drugs.

Sepsis in Pregnancy and the Puerperium: A Comparative Review of Major Guidelines.

Introduction: Sepsis is one of the leading causes of maternal morbidity and mortality worldwide and a major public health concern, often associated with delayed diagnosis, suboptimal management, and poor perinatal outcomes. Objectives: The aim of this study was to review and compare the most recently published influential guidelines on the prevention, diagnosis, and management of this complication during antenatal, intrapartum, and postpartum periods. Evidence Acquisition: A descriptive review of guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG), the Society for Maternal-Fetal Medicine (SMFM), the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ), the World Health Organization (WHO), and the Society of Obstetricians and Gynecologists of Canada (SOGC) on maternal and puerperal sepsis was carried out. Results: RCOG, SMFM, and SOMANZ provide guidance on the diagnosis and management of sepsis in pregnancy and the puerperium, whereas the WHO and the SOGC refer only to the prevention of peripartum infections. There is a consensus among the reviewed guidelines that a detailed personal history, along with physical examination, cultures, laboratory tests, and appropriate imaging, is the mainstay in sepsis diagnosis; however, there are several discrepancies regarding the diagnostic criteria. On management, the necessity of broad-spectrum antibiotics administration, within the first hour from recognition, and early source control are underlined by RCOG, SMFM, and SOMANZ. Furthermore, adequate fluid resuscitation with crystalloids is required, targeting for a mean arterial pressure (MAP) >65 mm Hg, whereas persistent hypotension or tissue hypoperfusion should be managed with vasopressors. In addition, RCOG, SMFM, and SOMANZ agree that increased fetal surveillance is warranted in case of maternal sepsis and point out that the decision regarding the optimal time of delivery should be guided according to maternal and fetal condition. In case of preterm labor, the use of corticosteroids should be considered. Moreover, SOMANZ and SMFM recommend thromboprophylaxis for septic women. With regards to prevention of peripartum infections, the WHO recommends prophylactic antibiotic administration in case of cesarean delivery, group B Streptococcus colonization, manual placenta removal, third/fourth-degree perineal tears, and preterm premature rupture of membranes, while discouraging antibiotics in case of preterm labor with intact membranes, prelabor rupture of membranes at term, meconium-stained amniotic fluid, uncomplicated vaginal birth, episiotomy, and operative vaginal delivery. Finally, SOGC, although supporting antibiotic prophylaxis for cesarean delivery and third/fourth-degree perineal injury, does not recommend this intervention in case of manual placenta removal, postpartum dilatation, and curettage for retained products of conception, operative vaginal delivery, and cervical cerclage. Conclusions: Sepsis remains a significant contributor of maternal morbidity and mortality with a constantly rising global incidence, despite the advances in diagnostic and therapeutic techniques. Thus, the development of consistent international practice protocols for the prevention, timely recognition, and effective management of this complication both in pregnancy and in the puerperium seems of paramount importance to safely guide clinical practice and subsequently improve perinatal outcomes.

Biopharmaceuticals against substance use disorders - Present and future.

BACKGROUND AND OBJECTIVES: Pharmacological treatments available for substance use disorder (SUD) focus on pharmacodynamics, agonizing or antagonizing the drug of abuse (DOA) on receptor level. Drawbacks of this approach include the reliance on long-term patient compliance, on-target off-site effects, perpetuation of addiction and unavailability for many DOAs. Newer, pharmacokinetic approaches are needed that restrict DOA's access to the brain or disrupt DOA-instated brain changes maintaining addiction. Biotechnology might be able to provide the right biopharmaceutical tools to deliver a fine-tuned solution with less side effects compared to currently available treatments. METHODS: This review examines the available literature on biopharmaceuticals developed to treat SUD. RESULTS: Active and passive immunization, metabolic enhancers that augment DOA metabolism and clearance, as well as genetic/epigenetic modulation are promising next generation SUD treatments. Active immunization relies on production of antidrug antibodies by means of vaccination, while passive immunization constitutes of exogenous administration of such antibodies. Metabolic enhancers include drug-specific metabolizing enzymes that can be administered or secreted by modified skin grafts, as well as catalytic antibodies that hasten DOA metabolism. Nanotechnological advances can also allow for brain delivery of siRNAs, mRNAs or DNA in order to modulate central, common in all addictions, genetic or epigenetic targets attenuating drug seeking behavior and reversing drug-induced brain changes. CONCLUSIONS: and Scientific Significance: Biopharmaceuticals can in the future complement or even replace traditional pharmacodynamics approaches in SUD treatment. While passive and active immunization biopharmaceuticals have entered human clinical trials, metabolic enhancers and genetic approaches are at the preclinical level.

COVID-19 vaccines adverse events: potential molecular mechanisms.

COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell's palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.

Safety and Monitoring of the Treatment with Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS).

BACKGROUND: Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS) are widely used given their proven efficacy in the relapsing form of the disease, while recently, Siponimod and Ocrelizumab have been approved for the progressive forms of the disease. Currently, 22 diseasemodifying drugs are approved by the FDA, while in 2012, only nine were present in the market. From March 2019 until August 2020, six new drugs were approved. This rapid development of new DMTs highlighted the need to update our knowledge about their short and long-term safety. OBJECTIVE: This review summarizes the available safety data for all the Disease-Modifying Therapies for Multiple Sclerosis and presents the monitoring plan before and during the treatment. METHODS: A literature search was conducted using PUBMED and COCHRANE databases. Key journals and abstracts from major annual meetings of Neurology, references of relevant reviews, and relative articles were also manually searched. We prioritized systematic reviews, large randomized controlled trials (RCTs), prospective cohort studies, and other observational studies. Special attention was paid to guidelines and papers focusing on the safety and monitoring of DMTs. CONCLUSION: Data for oral (Sphingosine 1-phosphate (S1P) receptor modulators, Fumarates, Teriflunomide, Cladribine), injectables (Interferons, Glatiramer acetate, Ofatumumab), and infusion therapies (Natalizumab, Ocrelizumab, Alemtuzumab) are presented.

Effects of GABAergic Agents on Multiple Sclerosis. A Narrative Review of In-vivo Models.

BACKGROUND: Multiple sclerosis (MS) is a lifelong deteriorating disease characterized by multiple heterogeneous symptoms. Being an autoimmune disease of the central nervous system, mainly affecting the myelin sheath of the nerves ordinarily results in neurological symptoms. GABA has numerous effects on the immune cells, altering cytokine production, cell migration and proliferation. Immune cells express GABA receptors making GABA an inflammation modulator. Therefore, GABAergic- associated agents could provide a compatible add-on therapy for MS patients alleviating their symptoms and providing better quality years. OBJECTIVE: This review aims to highlight and provide evidence of the potential benefits of a secondary treatment option in MS patients, aiming to better manage this disease. METHODS: We conducted a literature search through PubMed, Scopus and Google Scholar for GABA agonists, antagonists and modulators used in the in vivo model of experimental autoimmune encephalomyelitis (EAE), taking into consideration certain inclusion and exclusion criteria. RESULTS: In vivo studies for GABA-a and GABA-b agonists and modulators showed regulation of the autoimmune response in EAE mice. Increased preservation of myelinated sensitive fibers and diminished axonal damage in the CNS was also demonstrated. Further, decreased mononuclear inflammatory infiltration, pro-inflammatory cytokines reduction and reduced levels of Reactive oxygen species (ROS) were also reported. Biological results included decreased peak disease severity, duration, clinical scores and EAE incidence in the treatment groups. CONCLUSION: GABA agonists and modulators efficiently challenged different aspects of disease pathophysiology in vivo models of EAE. The studies showed a significant relevance of neuroprotection via modulation of the autoimmune response in EAE rats, indicating that they should be considered proper therapeutic candidates for clinical use, while also further clinical studies could empower their administration in clinical practice.

The effect of menopausal hormone therapy on the risk of melanoma and keratinocyte skin cancer: A systematic review and meta-analysis of observational studies.

BACKGROUND: Whether menopausal hormone therapy (MHT) increases the risk of skin cancer is controversial. AIM: To systematically review and meta-analyze evidence regarding the association of MHT with the risk of melanoma and keratinocyte cancer (KC). MATERIAL AND METHODS: A comprehensive literature search was conducted of the PubMed, Scopus and Cochrane databases, through to 30 October 2021. Skin neoplasms were divided into melanoma and KC. In the latter category, both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were considered. The results are presented as hazard ratios (HR) with 95 % confidence intervals (CI). The I2 index was used to assess heterogeneity. Subgroup analysis and sensitivity analysis were also conducted in order to explore potential differences among studies. RESULTS: Twenty-seven studies were included in the qualitative and 23 in the quantitative analysis, with a total of 2,612,712 menopausal women (25,126 with skin cancer; 20,150 with melanoma). MHT was associated with an increased risk of melanoma (HR 1.11; 95 % CI 1.05-1.19; I2 45%). With regard to MHT type, both estrogen monotherapy (HR 1.22, 95 % CI 1.16-1.29; I2 0%) and estrogen in combination with progestogen (HR 1.11, 95 % CI 1.05-1.18, I2 26%) significantly increased that risk. Regarding melanoma subtype, superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) were the only histologic subtypes associated with MHT use. MHT was also associated with an increased risk of KC (HR 1.17, 95 % CI 1.04-1.31, I2 83%), specifically BCC (HR 1.22, 95 % CI 1.12-1.32; I2 29%). Longer duration (>5 years) of MHT, current use and estrogen monotherapy were associated with an increased KC risk compared with no use. CONCLUSION: The use of MHT by postmenopausal women was associated with an increased risk of melanoma and KC. This risk was higher for current MHT users and those treated for over 5 years.

Serum Proteome Signatures of Anti-SARS-CoV-2 Vaccinated Healthcare Workers in Greece Associated with Their Prior Infection Status.

Over the course of the pandemic, proteomics, being in the frontline of anti-COVID-19 research, has massively contributed to the investigation of molecular pathogenic properties of the virus. However, data on the proteome on anti-SARS-CoV-2 vaccinated individuals remain scarce. This study aimed to identify the serum proteome characteristics of anti-SARS-CoV-2 vaccinated individuals who had previously contracted the virus and comparatively assess them against those of virus-naïve vaccine recipients. Blood samples of n = 252 individuals, out of whom n = 35 had been previously infected, were collected in the "G. Gennimatas" General Hospital of Thessaloniki, from 4 January 2021 to 31 August 2021. All participants received the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). A label-free quantitative proteomics LC-MS/MS approach was undertaken, and the identified proteins were analyzed using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes) databases as well as processed by bioinformatics tools. Titers of total RBD-specific IgGs against SARS-CoV-2 were also determined using the SARS-CoV-2 IgG II Quant assay. A total of 47 proteins were significantly differentially expressed, the majority of which were down-regulated in sera of previously infected patients compared to virus-naïve controls. Several pathways were affected supporting the crucial role of the humoral immune response in the protection against SARS-CoV-2 infection provided by COVID-19 vaccination. Overall, our comprehensive proteome profiling analysis contributes novel knowledge of the mechanisms of immune response induced by anti-SARS-CoV-2 vaccination and identified protein signatures reflecting the immune status of vaccine recipients.