Long-Term Results of Immunogenicity of Booster Vaccination against SARS-CoV-2 (Hybrid COV-RAPEL TR Study) in Turkiye: A Double-Blind, Randomized, Controlled, Multicenter Phase 2 Clinical Study.

The immunogenicity of vaccines decreases over time, causing a need for booster doses. This study aimed to present the long-term (Day 84) immunogenicity results of the double-blind, randomized, controlled, phase II Hybrid COV-RAPEL TR Study (NCT04979949), in which the TURKOVAC or CoronaVac vaccines were used as a booster after the second dose of primary vaccination with CoronaVac. A total of 190 participants from the Hybrid COV-RAPEL TR Study, who had both Day 28 and Day 84 immunogenicity results, were included. The immunogenicity on Day 84, regarding the neutralizing antibody positivity (Wuhan and Delta variants) and anti-spike immunoglobulin (Ig) G (IgG) antibody positivity, was compared between TURKOVAC and CoronaVac vaccine arms according to sex and age groups. Overall, antibody positivity showed a slight decrease on Day 84 vs. Day 28, but was not different between TURKOVAC and CoronaVac arms either for sexes or for age groups. However, TURKOVAC produced better antibody response against the Delta variant than CoronaVac, while CoronaVac was superior over TURKOVAC regarding neutralizing antibody positivity in the 50-60 years age group, regardless of the variant. A single booster dose, after the completion of the primary vaccination, increases antibody positivity on Day 28 which persists until Day 84 with a slight decrease. However, an additional booster dose may be required thereafter, since the decrease in antibody titer may be faster over time.

Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18-60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

What is the context? The timing of the primary and booster doses for each vaccine differs.We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.What is new? The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.What is the impact? With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4­6 month interval.Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

The Effects of the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin, Cannabinoid Agonist WIN 55,212-2, and Nitric Oxide Synthase Inhibitor Nω-Nitro-L-Arginine Methyl Ester Hydrochloride on the Serotonin and Dry Skin-Induced Itch.

INTRODUCTION: In many types of itch, the interaction between immune system cells, keratinocytes, and sensory nerves involved in the transmission of itch is quite complex. Especially for patients with chronic itching, current treatments are insufficient, and their quality of life deteriorates significantly. OBJECTIVE: In this study, we aimed to investigate the role of the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), cannabinoid agonist WIN 55,212-2, and nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in pruritus. METHODS: We created a serotonin (5-HT)-induced (50 µg/µL/mouse, i.d.) acute and acetone-ether-water (AEW)-induced chronic itching models. 17-AAG (1, 3, and 5 mg/kg, intraperitoneally [i.p.]), WIN 55,212-2 (1 mg/kg, i.p.), and L-NAME (1 mg/kg, i.p.) were applied to Balb/c mice. RESULTS: We found that 17-AAG suppressed the scratches of mice, depending on the dose. The itch behavior was reduced by WIN 55,212-2, but L-NAME showed no antipruritic effect at the administered dose. The combined application of these agents in both pruritus models showed synergism in terms of the antipruritic effect. Our results showed that NO did not play a role in the antipruritic effect of WIN 55,212-2 and 17-AAG. Increased plasma IgE levels with AEW treatment decreased with the administration of 17-AAG (5 mg/kg, i.p.) and WIN 55,212-2. CONCLUSION: These results demonstrate that Hsp90 may play a role in the peripheral pathway of pruritus, and cannabinoid agonists and Hsp90 inhibitors can be used together in the treatment of pruritus.

Fear-conditioned alterations of motor cortex excitability: The role of amygdala.

BACKGROUND AND OBJECTIVE: We hypothesized that fear-conditioning may increase motor cortical excitability in preparation for response to fear. We tested our hypothesis in healthy subjects and in the second step, to determine the role of amygdala in alterations of motor cortex excitability, we included a group of patients who previously underwent unilateral amygdalo-hippocampectomy for temporal lobe epilepsy. PATIENTS AND METHODS: In the first step, we included 16 healthy volunteers. In the second step, 14 patients who previously underwent unilateral amygdalo-hippocampectomy for temporal lobe epilepsy and who were seizure-free were included in the study. Motor evoked potentials (MEPs) recorded over right hand were recorded twice before and after the observation of fearful faces (fear-conditioning). Auditory startle response (ASR) was also recorded. RESULTS: Comparisons of before and after fear-conditioning MEP parameters within the healthy subjects group showed MEP amplitude was higher after fear-conditioning (p=0.019). Same comparison in patients with unilateral amygdalo-hippocampectomy demonstrated shorter MEP latency (p=0.036) and higher MEP amplitudes after fear-conditioning (p=0.046). CSPs did not show any change after this paradigm in both groups. Comparisons of ASR findings before and after fear-conditioning demonstrated enhanced responses after fear-conditioning in both healthy subjects and in patients with unilateral amygdalo-hippocampectomy. For MEPs or ASRs, there was a similar enhancement in patients with left- or right-sided operation. CONCLUSIONS: Fear-potentiation of both corticospinal and reticulospinal pathways occurs in healthy humans and bilateral potentiation of ASR and potentiation of MEPs are maintained even after resection of unilateral amygdala regardless of its side.

Contribution of FDG-PET in epilepsy surgery: consistency and postoperative results compared with magnetic resonance imaging and electroencephalography.

AIM: Surgery is a treatment option for medically intractable epilepsy patients. Abnormalities in regional cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have predictive prognostic value in evaluating the outcome of epilepsy surgery. This study investigated the efficacy of FDG-PET for delineation of the epileptogenic zone (EZ) by comparing its consistency with other diagnostic tools and surgical outcome. MATERIAL AND METHODS: We analyzed the results of 121 consecutive patients evaluated for epilepsy surgery. FDG-PET results were crosschecked with magnetic resonance imaging (MRI) and electroencephalography (EEG) results, as well as postoperative outcome and pathology. RESULTS: FDG-PET findings of 75 patients (62 %) were concordant with MRI (Mc-Nemar-χ2 test p=0.024, Kappa=0.22). Further, the PET findings were consistent with EEG, and was statistically significant, according to Post-hoc test, in temporal epilepsy (TLE) group (χ2=8.21 P=0.04). Both investigations revealed localizing information in 56 (46.2%) patients. Twenty-six (72.2%) MRI-negative patients had hypometabolism on PET. The pathology of the 10 PET-negative patients was 5 cases of mesial temporal sclerosis, 2 cortical dysplasia, 2 gliosis and one tumor. Seven (70%) of these patients' lesions originated from the temporal lobe. FDG-PET had correctly predicted the EZ in 37 (86%) of 43 patients who underwent surgery. CONCLUSION: FDG-PET results may not be strongly associated with EZ but represent an additional tool in delineation of EZ during the noninvasive phase of presurgical evaluation.

Presentation of an unusual patient with Lafora disease.

Lafora disease is a rare, fatal, autosomal recessive progressive myoclonic epilepsy. The condition is characterised by seizures, myoclonus and dementia. In this case report, a patient who presented with generalised tonic-clonic seizures at the age of 30 is discussed. Until the age of 48, the patient did not have myoclonic jerks or ataxia clinically, but had well controlled seizures. He developed dementia and late extrapyramidal signs. Axillary skin biopsy revealed typical Lafora inclusion bodies. Genetic analysis showed a mutation in the EMP2B gene. To our knowledge, this is the first description of a patient suffering from a Lafora disease without disabling myoclonus and ataxia but rather rare seizures, extrapyramidal signs, and dementia.

Auditory-evoked masseter inhibitory reflex.

We aimed to investigate auditory-evoked masseter inhibitory reflex and discuss possible auditory-trigeminal pathways in brainstem. Our study population consisted of 21 healthy volunteers (age-matched 7 males and 14 females). Bilateral electrical blink reflex (BR), auditory blink reflexes (ABR) and electrical MIR (MIR) were studied. After obtaining normal potentials, auditory MIR (AMIR) was studied. Electrical blink reflexes had two components as R1 and R2, and ABR had one evoked potential in all volunteers. There was no significant difference between gender, nor between right- and left-sided BR and ABR. The mean latency of ABR responses were shorter than latencies of R2 phase of BR (p=0.013 for left-sided responses, p=0.035 for right-sided responses). Electrical stimulation revealed two suppression periods (SP1 and SP2) in MIR responses bilaterally in all volunteers. Auditory stimulation evoked typical two suppression periods only in 11 subjects (5 males, 6 females). The mean latency of SP1 component of AMIR was significantly longer than those of MIR bilaterally in both males and females, while the SP2 component had a shorter onset. The durations of SP1, SP2 and total SP were always shorter than those obtained in MIR with smaller degree of suppressions. None of the MIR or AMIR responses showed significance difference between sexes. We assume that auditory-evoked MIR might share the similar interneurons as with other electrical or nociceptive stimulation, which connects cochlear-trigeminal neurons via pontine reticular system to premotor area for masseter muscle.