Towards a predictive model of COVID-19 vaccine hesitancy among American adults.

Designing effective public health campaigns to combat COVID-19 vaccine hesitancy requires an understanding of i) who the vaccine hesitant population is, and ii) the determinants of said population's hesitancy. While researchers have identified a number of variables associated with COVID-19 vaccine hesitancy that could inform such campaigns, little is known about the cumulative or relative predictive power of these factors. In this article, we employ a machine learning model to analyze online survey data collected from 3353 respondents. The model incorporates an array of variables that have been shown to impact vaccine hesitancy, allowing us to i) test how well we can predict vaccine hesitancy, and ii) compare the relative predictive impact of each covariate. The model allows us to correctly classify individuals that are vaccine acceptant with 97% accuracy, and those that are vaccine hesitant with 72% accuracy. Trust in and knowledge about vaccines is, by far, the strongest predictor of vaccination choice. While our results demonstrate that public health campaigns designed to increase vaccination rates must find a way to increase public trust in COVID-19 vaccines, our results cannot speak to the malleability of such beliefs, nor how to enhance trust.

The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats.

BACKGROUND: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. AIMS: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. STUDY DESIGN: Animal experiment. METHODS: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. RESULTS: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42(nd) day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of nerve regeneration in group 1 and the lowest in group 3. However, this difference was not statistically significant. Moreover, there was no significant difference in the bone mineral density (BMD) levels among the groups. CONCLUSION: We believe that a daily single dose of sildenafil plays an important role in the treatment of sciatic nerve damage and bone healing and thus can be used as supportive clinical treatment.

Evaluation of the cardiovascular effects of varenicline in rats.

BACKGROUND: Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events. OBJECTIVE: To determine the cardiovascular toxicity induced by varenicline in rats. MATERIALS AND METHODS: We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 µg/kg/day varenicline on days 1-3, 9 µg/kg twice daily on days 4-7, and 18 µg/kg twice daily on days 8-90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed. RESULTS: Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups. CONCLUSION: Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation.

Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity.

BACKGROUND: Cisplatin, an effective chemotherapeutic agent, is used for the treatment of several types of cancers. However, cisplatin has some severe side effects such as nephrotoxicity. On the other hand, molsidomine, a NO donor, has anti-oxidative and vasodilator effects. OBJECTIVES: The aim of this study was to estimate the protective effects of molsidomine on cisplatin-induced nephrotoxicity. MATERIAL AND METHODS: Thirty-two rats were randomly divided into 4 groups as follows: (1) control; (2) received a single-dose intraperitoneal (i.p.) injection of 5 mg/kg cisplatin; (3) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days before cisplatin treatment; (4) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days. The specific biochemical markers, including antioxidants, and the histopathological alterations were evaluated. RESULTS: Cisplatin significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) levels and decreased glutathione peroxidase (GPX) level. Molsidomine significantly decreased MPO level nearly to control level; however, its ameliorating effects on MDA, SOD, CAT and GPX did not reach to significant levels. Cisplatin-induced elevation of blood-urea-nitrogen and serum-creatinine were diminished after molsidomine administration. Cisplatin also induced severe tubular degeneration, nuclear condensation, apoptosis and scattered patchy inflammation in the histological examination. Molsidomine improved all of these histological damages. CONCLUSIONS: In this study, the beneficial effect of molsidomine against cisplatin nephrotoxicity has been evaluated for the first time.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

Protective effects of melatonin against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cardiac injury in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototype of a group of highly toxic environmental chemicals. Although there are some suggestions regarding TCDD-induced cardio-toxicity, the exact mechanisms underlying this process have not been fully discovered. One mechanism related to this toxicity is believed to be the generation of reactive oxygen species. Melatonin is known to be a strong antioxidant and has a free radical scavenging ability. Therefore, the aim of this study was to investigate the TCDD-induced cardio-toxicity and the protective effects of melatonin in rats. Rats were randomly divided into 4 equal groups (n=7 for each group). Group 1 was control; group 2 was TCDD group (2µg/kg/week, p.o); group 3 was melatonin group (5mg/kg/day, i.p.) and group 4 was TCDD and melatonin treatment group. All agents were continued to be administered until the 45th day. Body/heart weights, mean oxygen saturation (PO2%), hemodynamic [mean blood pressure (MBP) and heart rate (HR) from the cannulated-carotid artery] and electrocardiographic evaluations (arrhythmias and duration of PR, QRS and QT intervals), biochemical and histopathological analysis were carried out. TCDD exposure caused significant body and heart weight loss, impairment of PO2%, and decrease of MBP and HR levels. Also, major ECG changes and prolongation of PR, QRS and QT durations were observed in TCDD-exposed rats. In biochemical analysis, TCDD significantly induced lipid peroxidation and reduced antioxidant activities. Moreover, our histopathological observations were in accordance with the biochemical results. According to the results, melatonin treatment significantly protected the subjects from TCDD-induced cardio-toxicity.

Protective effect of sitagliptin against renal ischemia reperfusion injury in rats.

This study was designed to investigate the protective effects of sitagliptin on renal damage induced by renal ischemia reperfusion (I/R) in rats. For this, rats were randomly divided into four groups (n = 8): (1) sham group, in which the rats only underwent right nephrectomy; (2) right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group (I/R); (3) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks; (4) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks before left kidney I/R (n = 8). Sitagliptin-treated rats that underwent renal I/R demonstrated significant decrease in the serum urea nitrogen and creatinine and also, lipid peroxidation, total oxidant status and malondialdehyde level in the renal tissue when compared to the renal I/R group. Additionally, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase and total antioxidative capacity were significantly increased after renal I/R in sitagliptin-treated rats. Our histopathological findings were in accordance with these biochemical results. In sum, in the current study all of our results indicated that sitagliptin treatment ameliorated renal damage induced by renal I/R in rats.

The protective effect of apocynin on testicular ischemia-reperfusion injury.

PURPOSE: We investigated the protective effect of the NADPH oxidase inhibitor apocynin on testicular damage induced by ischemia-reperfusion injury in rats. MATERIALS AND METHODS: A total of 32 rats were randomly divided into 4 groups. Controls underwent left scrotal exploration only. The 3 groups with ischemia-reperfusion underwent 4-hour torsion followed by 1-hour detorsion. The ischemia-reperfusion only group underwent left testicular torsion and detorsion. The ischemia-reperfusion plus saline group underwent left testicular torsion, received 10 ml/kg saline intraperitoneally at minute 210 of ischemia and then underwent detorsion. The ischemia-reperfusion plus apocynin group underwent left testicular torsion, received 20 mg/kg apocynin intraperitoneally at minute 210 of ischemia and then underwent detorsion. We determined histopathological findings and performed specific biochemical analyses. RESULTS: In the ischemia-reperfusion only and the ischemia-reperfusion plus saline groups malondialdehyde, total oxidative capacity and the oxidative stress index were significantly higher. Superoxide dismutase, catalase, glutathione peroxidase and glutathione were significantly lower. Apocynin significantly decreased malondialdehyde, total oxidative capacity and the oxidative stress index, and significantly increased superoxide dismutase and catalase. There was a significantly increase in the number of giant, degenerated and desquamated cells in the ischemia-reperfusion group. Apocynin significantly improved these histological alterations. CONCLUSIONS: These histopathological and biochemical findings show the beneficial effects of apocynin on testicular ischemia-reperfusion injury.

Molsidomine prevents cisplatin-induced hepatotoxicity.

BACKGROUND AND AIMS: Despite its beneficial effects, cisplatin has considerable nephrotoxic, ototoxic, neurotoxic and hepatotoxic side effects. It has been documented that reactive oxygen radical species are involved with the pathophysiology of cisplatin-induced hepatotoxicity. Molsidomine (MOL) can exert antioxidant and anti-inflammatory effects. Therefore, the current study was planned to determine the effects of cisplatin on the liver oxidant/antioxidant system and the possible protective effects of (MOL) on liver toxicity. METHODS: Animals were divided into four groups as follows: (1) control; (2) MOL; (3) cisplatin and (4) MOL plus cisplatin group. Biochemical and histopathological evaluations were performed on the extracted liver tissue. Also, serum levels of serum aspartate transaminase (AST) and serum alanine transaminase (ALT) were determined. RESULTS: Our results clearly indicated that liver antioxidant enzyme activities and ALT levels were significantly decreased, whereas lipid peroxidation and neutrophil accumulation were increased in the cisplatin-treated animals (5 mg/kg single dose, i.p.) compared to the control rats. MOL treatment (4 mg/kg/day, i.p.) for 3 consecutive days provided a significant protection against cisplatin-induced hazardous changes in the liver tissue. Our histopathological findings including caspase-3 activity were also in accordance with the biochemical results. CONCLUSIONS: We propose that MOL acts in the liver as a potent scavenger of free radicals, anti-inflammatory and anti-apoptotic effects to prevent the toxic effects of cisplatin, both at the biochemical and histopathological levels.

The protective effects of apocynin on kidney damage caused by renal ischemia/reperfusion.

PURPOSE: This experimental study was designed to explore the protective effect of apocynin, the NADPH-oxidase inhibitor, on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. METHODS: Thirty-two rats were randomly divided into a control group and three I/R groups (1-hour ischemia followed by 23-hour reperfusion). Three I/R groups were treated by apocynin (20 mg/kg, i.p.) at two different time points (before ischemia and during ischemia). The histopathological findings, including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GPX), reduced glutathione (GSH), myeloperoxidase (MPO), blood urea nitrogen (BUN), and serum creatinine (Cr) levels, were determined. RESULTS: Kidney tissue MDA and MPO, and serum BUN and Cr levels were found to be significantly higher in the I/R group, but there was no statistically significant difference in the levels of SOD, CAT, GPX, and GSH between the I/R and the control groups. Although apocynin significantly reduced MDA and MPO in group 3 and increased GPX in both treatment groups when compared to the I/R group, the elevated BUN and Cr levels were significantly reduced in treatment groups. Renal I/R injury also induced extensive tubular necrosis, glomerular damage, and apoptosis in the histological evaluation. Apocynin, especially when used during ischemia, ameliorated these histological damages in different amounts in treatment groups. CONCLUSION: The beneficial effects of apocynin on renal I/R injury were evaluated for the first time.

Effects of ozone therapy on cyclophosphamide-induced urinary bladder toxicity in rats.

PURPOSE: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC). METHODS: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples. RESULTS: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05). CONCLUSION: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.

Effects of dexmedetomidine and midazolam on motor coordination and analgesia: a comparative analysis.

OBJECTIVE: We compared the effects of 2 sedative drugs, dexmedetomidine and midazolam, on motor performance and analgesic efficacy in a rat model. MATERIALS AND METHODS: Rats were randomly divided into the following 4 groups on the basis of the treatment received. The first group received 83 µg/kg/min midazolam; the second, 1 µg/kg/min dexmedetomidine; the third, 83 µg/kg/min morphine; and the fourth was a control group. The rats were measured motor coordination and pain reflexes by using rotarod, accelerod, hot plate, and tail flick tests. RESULTS: At all the tested speeds, the midazolam-injected rats remained on the rotarod longer than did the dexmedetomidine-injected rats. Furthermore, in the 10-minute accelerod test, the midazolam-injected rats remained for a longer duration than did the dexmedetomidine-injected rats. The latency time for the hot plate test was significantly higher at 10 minutes and 20 minutes in the dexmedetomidine group than in the midazolam group. Further, the latency time at 10 minutes for the tail flick test was greater in the dexmedetomidine group than in the midazolam group. CONCLUSIONS: In this rat model, midazolam results in faster recovery of motor coordination performance when compared with dexmedetomidine.

Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats.

BACKGROUND/AIMS: This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. METHODS: Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. RESULTS: Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. CONCLUSION: In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time.

Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for urinary tract infection: assessment of protective effects in a rat model.

OBJECTIVE: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. METHODS: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. RESULTS: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 × 10(3) cfu/mL) and chondroitin sulfate (1 × 10(4) cfu/mL) groups relative to the control group (5 × 10(4) cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 × 10(2) cfu/mL; P < 0.05). In the bladder tissues, statistically significant decreases in median bacterial growth rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium damage decreased in the treatment groups. However, this effect was prominent in hyaluronic acid + chondroitin sulfate group. CONCLUSION: Our experimental findings show that the hyaluronic acid + chondroitin sulfate combination has a potential benefit in reducing the bacterial load in urine and the thickness of the transitional epithelium.