3D-printing of alginate/gelatin scaffold loading tannic acid@ZIF-8 for wound healing: In vitro and in vivo studies.

In the present study, ZIF-8 metal-organic framework (MOF) modified with Tannic acid (TA@ZIF-8) was synthesized and impregnated in alginate-gelatin (Alg-Gel) hydrogel. The Alg-Gel scaffolds containing 0, 5, and 10 % of TA@ZIF-8 were fabricated through the 3D printing method specifically denoted as Alg-Gel 0 %, Alg-Gel 5 %, and Alg-Gel 10 %. XRD, FTIR, FESEM, and EDX physically and chemically characterized the synthesized ZIF-8 and TA@ZIF-8 MOFs. Besides, Alg-Gel containing TA@ZIF-8 prepared scaffolds and their biological activity were also evaluated. SEM images verified the nano-size formation of MOFs. Improved swelling and decreased degradation rates after adding TA@ZIF-8 were also reported. Increased compression strength from 0.628 to 1.63 MPa in Alg-Gel 0 % and Alg-Gel 10 %, respectively, and a 2.19 increase in elastic modulus in Alg-Gel 10 % scaffolds were exhibited. Biological activity of scaffolds, including Live-dead and Cell adhesion, antibacterial, in-vivo, and immunohistochemistry assays, demonstrated desirable fibroblast cell proliferation and adhesion, increased bacterial growth inhibition zone, accelerated wound closure and improved expression of anti-inflammatory cytokines in Alg-Gel 10 % scaffolds. The findings of this study confirm that Alg-Gel 10 % scaffolds promote full-thickness wound healing and could be considered a potential candidate for full-thickness wound treatment purposes.

Cilostazol pretreatment prevents PTSD-related anxiety behavior through reduction of hippocampal neuroinflammation.

Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions. Furthermore, PDEIs have shown some promise in animal models of PTSD. However, the current model of PTSD pathogenesis, which is based on dysregulated fear learning, implies that PDE inhibition in neurons should enhance the acquisition of fear memory from the traumatic event. As a result, we hypothesized that PDEIs may improve PTSD symptoms through inhibiting neuroinflammation rather than long-term potentiation-related mechanisms. To this end, we tested the therapeutic efficacy of cilostazol, a selective inhibitor of PDE3, on PTSD-related anxiety symptoms in the underwater trauma model of PTSD. PDE3 is expressed much more richly in microglia and astrocytes compared to neurons in the murine brain. Furthermore, we used hippocampal indolamine 2,3-dioxygenase 1 (IDO) expression and interleukin 1 beta (IL-1ß) concentration as indicators of neuroinflammation. We observed that cilostazol pretreatment prevented the development of anxiety symptoms and the increase in hippocampal IDO and IL-1ß following PTSD induction. As a result, PDE3 inhibition ameliorated the neuroinflammatory processes involved in the development of PTSD symptoms. Therefore, cilostazol and other PDEIs may be promising candidates for further investigation as pharmacological therapies against PTSD.

Development of preeclampsia in pregnant women with white-coat hypertension: a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a hypertensive disease characterized by an increased clinic blood pressure but normal home or workplace blood pressure. Due to variable prevalence, a subset of women with WCH may be incorrectly diagnosed with chronic hypertension, highlighting the need for accurate diagnosis. Little is known about the role of WCH in pregnancy, but a meta-analysis aims to determine whether WCH increases the likelihood of developing preeclampsia. METHODS: A systematic review and meta-analysis was conducted to determine whether there is an association between WCH and the incidence of preeclampsia in pregnant women. The search included PubMed, Embase, and Scopus databases until February 2023, using PRISMA guidelines. Pregnant women with apparent office hypertension throughout pregnancy who underwent 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring were included. Meta-analysis was performed using RevMan. RESULTS: This study included 12 studies with a total of 4,672 pregnant women and found that women with WCH have a higher risk of developing preeclampsia compared to normotensive women (RR: 2.29, 95% CI [1.18,4.43], P = 0.01). However, when compared with pregnant women with gestational hypertension or chronic hypertension, women with WCH had a significantly lower risk of developing preeclampsia ((RR: 0.39, [0.20,0.80], p=0.009) and (RR: 0.41, [0.27,0.62], P<0.001), respectively). CONCLUSION: The study recommends incorporating 24-hour ABPM into clinical practice to differentiate between chronic hypertension and WCH in early pregnancy and focus on special management for those who need it. The findings may guide future research on ABPM's role in diagnosing WCH and its effects on pregnancy outcomes.

Characterization and in vivo evaluation of a fabricated absorbable poly(vinyl alcohol)-based hernia mesh.

The most widely taken medical approach toward hernia repair involves the implementation of a prosthetic mesh to cover the herniated site and reinforce the weakened area of the abdominal wall. Biodegradable meshes can serve as biocompatible grafts with a low risk of infection. However, their major complication is associated with a high rate of degradation and hernia recurrence. We proposed a facile and cost-effective method to fabricate a poly(vinyl alcohol)-based mesh, using the solution casting technique. The inclusion of zinc oxide nanoparticles, citric acid, and three cycles of freeze-thaw were intended to ameliorate the mechanical properties of poly(vinyl alcohol). Several characterization, cell culture, and animal studies were conducted. Swelling and water contact angle measurements confirmed good water uptake capacity and wetting behavior of the final mesh sample. The synthesized mesh acquired a high mechanical strength of 52.8 MPa, and its weight loss was decreased to 39 %. No cytotoxicity was found in all samples. In vivo experiments revealed that less adhesion and granuloma formation, greater tissue integration, and notably higher neovascularization rate were resulted from implanting this fabricated hernia mesh, compared to commercial Prolene® mesh. Furthermore, the amount of collagen deposition and influential growth factors were enhanced when rats were treated with the proposed mesh instead of Prolene®.

Clinical features and outcomes of Myasthenia Gravis associated with COVID-19 vaccines: A systematic review and pooled analysis.

BACKGROUNDS: Myasthenia Gravis (MG), a chronic neuromuscular junction disorder, emerged as one of the serious side effects of the Coronavirus Disease 2019 (COVID-19) vaccination. We aimed to summarize the findings of studies on the clinical features and outcomes of COVID-19 vaccination-associated MG. METHODS: We performed a systematic search on 3 databases, Medline, Embase, and Scopus, using the query "COVID-19 vaccine" and "Myasthenia Gravis." Patients' data, including clinical data, MG subtype, vaccine type, and vaccine dose number, were extracted from the eligible studies. RESULTS: A total of 20 COVID-19 vaccination-related MGs have been reported worldwide. The median (interquartile range) age was 64 (51, 75) years; 85% (17/20) of them were male, and 70% (14/20) of patients had received messenger RNA-based vaccines. The most common symptoms, in order of frequency, were binocular diplopia (8/11) and ptosis (4/11); the median (interquartile range) time from vaccine to MG symptoms was 6 (2, 7.5) days. Repetitive nerve stimulation showed abnormal decrement in 85% (11/13) of patients, and all 4 patients getting single-fiber electromyography showed an abnormal finding. Nine out of twelve patients with data on clinical outcomes experienced partial/complete improvement of symptoms within 1 month. CONCLUSION: MG cases after the COVID-19 vaccine are more likely to occur among males and adults older than 50 years. Our pooled cohort data suggest MG symptoms appear within 2 weeks after receiving the vaccine. The presenting symptoms in MG cases associated with COVID-19 vaccine are possibly similar to non-vaccination related MGs. Most patients are expected to experience partial/complete improvement within 1 month.

Composite lipid indices in patients with obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: One of the most prevalent sleep disorders affecting the individual's daily life is obstructive sleep apnea (OSA), for which obesity is a major risk factor. Several novel lipid indices have been suggested to have associations with OSA, among which visceral adiposity index (VAI), atherogenic index of plasma (AIP), and lipid accumulation product (LAP) are the most important ones. Herein, the current study aimed to systematically investigate the association between these indices and OSA. METHODS: Four international databases, including PubMed, Scopus, the Web of Science, and Embase were searched in order to find relevant studies that investigated LAP, VAI, or AIP in OSA and compared them with non-OSA cases or within different severities of OSA. Random-effect meta-analysis was used to generate the standardized mean difference (SMD) and 95% confidence interval (CI) of the difference in lipid indices between OSA and non-OSA cases. Moreover, the pooled area under the receiver operating characteristic curves (AUCs) observed in individual studies for diagnosis of OSA based on these lipid indices were calculated by random-effect meta-analysis. RESULTS: Totally 14 original studies were included, comprised of 14,943 cases. AIP, LAP, and VAI were assessed in eight, five, and five studies, respectively. Overall, these lipid indices had acceptable diagnostic ability (AUC 0.70, 95% CI 0.67 to 073). Meta-analysis revealed that AIP was significantly higher in patients with OSA (SMD 0.71, 95% CI 0.45 to 0.97, P < 0.01). Moreover, AIP also increased in higher severities of OSA. Regarding LAP, a higher LAP was observed in OSA/patients with high risk for OSA rather than in controls/low risk for OSA (SMD 0.53, 95% CI 0.25 to 0.81, P < 0.01). VAI was also increased in OSA based on results from two studies. CONCLUSION: These findings suggest that composite lipid indices are increased in OSA. Also, these indices can have the potential beneficiary diagnostic and prognostic ability in OSA. Future studies can confirm these findings and enlighten the role of lipid indices in OSA.

Evaluation of the Farsi-translated Hemorrhoidal Disease Symptom Score and Short Health Scale questionnaires in patients with hemorrhoid disease: A cross-sectional study.

Background and Aims: The Hemorrhoidal Disease Symptom Score (HDSS) is a tool that is scored based on five main symptoms: pain, bleeding, itching, soiling, and prolapse. Furthermore, the Short Health Scale (SHS) is a measurement tool of subjective health and health-related quality of life. This study was performed to validate the Farsi-translated Hemorrhoidal Disease Symptom Score (HDSS), and Scale Short Health Scale adapted for hemorrhoidal disease (SHS-HD) as a measure of symptom severity in patients with hemorrhoid disease. Methods: In this study, HDSS and SHS-HD were translated into Farsi. Participants with confirmed hemorrhoid disease completed the questionnaire. Subsequently, the questionnaire's discriminative validity, convergent validity, reliability, sensitivity, and specificity were evaluated. Results: Data from 31 patients were analyzed (mean age 39.68; 71% male). The results of the analysis showed good internal consistency as Cronbach's α for HDSS and SHS were 0.994 and 0.995 respectively. Spearman's correlation coefficient for the test-retest comparison was 0.986 (p < 0.01). The responses demonstrated good convergent validity. Moreover, the comprehension and suitability of each question were rated as excellent (Pearson's correlation coefficient = 0.3). Conclusions: Our findings revealed that the Farsi translation of the HDSS and SHS-HD can be a valuable tool for evaluating the symptom severity in patients with hemorrhoid disease.

Assessment of the efficacy of Handmade Vacuum-Assisted Sponge Drain for Treatment of Anastomotic leakage after Low Anterior Rectal Resection.

Anastomotic leakage is one of the major complications of colorectal surgery, which might lead to reoperation, increased hospital stays, further intervention and mortality. Vacuum-assisted closure by devices such as Endo-SPONGE® produced by (B-Braun Medical B.V.) is currently being used to treat leakage and fistula. In this study, we aimed to assess the handmade vacuum-assisted sponge drain for anastomotic leakage following low anterior resection. This prospective study included 22 patients who had undergone sponge drain placement to treat anastomotic leakage. All patients had anastomotic leaks or defects after left anterior rectal resection (LAR) without ileostomy. They were treated with neo-adjuvant chemotherapy before the surgery and then subjected to rigid recto-sigmoidoscopy for 30 days following the operation. Any sign of leakage, such as perianal and pelvic pain, was immediately identified and followed up with a CT scan and another recto-sigmoidoscopy. Twenty-two patients were enrolled in this study, 12 men (54.5%) and 10 women (47.4%). All patients had received neo-adjuvant chemotherapy with an average follow-up of 22.30 ± 3.81. 75% of patients (15 cases) were successfully treated, and 17 patients (85%) underwent successful ostomy closure. Treatment failed in 5 patients (25%), including three men and two women. This study shows that handmade vacuum-assisted sponge drain is a cost-effective method of anastomotic leakage management with efficacy similar to that of Endo-SPONGE®.

Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats.

Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.

Simple Separate Sutures Versus Continuous Sutures on Hepatic Artery Anastomosis in Liver Transplant: A Prospective Study.

OBJECTIVES: Liver transplant is the definitive treatment for liver failure of various causes. There are various operation methods, of which the conventional approach is most frequently performed. In the conventional technique, 4 anastomoses are required, and different subtleties in these techniques are known to cause different rates of complications. We assessed the outcome of a simple separate (ie, interrupted) suture technique compared with a the continuous suture technique in 194 patients. MATERIALS AND METHODS: There were 194 patients included in this single-center, controlled study. The exclusion criteria were patients who died during the surgical procedure and patients with incomplete medical records. The data recorded were age, sex, past medical history of liver disease, tobacco use, comorbidities, and whetherthe livertransplant was for the first time or retransplant. All patients included in this study were recipients of liver transplants from deceased donors. The patients were categorized as those who received either simple sutures (n = 16) or continuous sutures (n = 178). The continuous suture operations were performed first, and the simple suture operations were performed at a later time (ie, the 2 groups were temporally separated). The results included the duration of surgery, hepatic artery thrombosis rate, hepatic artery stenosis rate, 2-year survival, and further complications. RESULTS: No evidence of hepatic artery thrombosis or hepatic artery stenosis was observed in the study groups. The duration of surgery was equal in both groups. The 2-year mortality rate was significantly higher in the simple suture group. CONCLUSIONS: The continuous suture method seems to be accompanied by a similar duration of operation and rate of complications compared with the simple suture process.

Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine's anxiogenic activity in an animal model of PTSD.

While SSRIs are the current first-line pharmacotherapies against post-traumatic stress disorder (PTSD), they suffer from delayed onset of efficacy and low remission rates. One solution is to combine SSRIs with other treatments. Neuronal nitric oxide synthase (nNOS) has been shown to play a role in serotonergic signaling, and there is evidence of synergism between nNOS modulation and SSRIs in models of other psychiatric conditions. Therefore, in this study, we combined subchronic fluoxetine (Flx) with 7-nitroindazole (NI), a selective nNOS inhibitor, and evaluated their efficacy against anxiety-related behavior in an animal model of PTSD. We used the underwater trauma model to induce PTSD in rats. Animals underwent the open field (OFT) and elevated plus maze tests on days 14 (baseline) and 21 (post-treatment) after PTSD induction to assess anxiety-related behaviors. Between the two tests, the rats received daily intraperitoneal injections of 10 mg/kg Flx or saline, and were injected intraperitoneally before the second test with either 15 mg/kg NI or saline. The change in behaviors between the two tests was compared between treatment groups. Individual treatment with both Flx and NI had anxiogenic effects in the OFT. These effects were associated with modest increases in cFOS expression in the hippocampus. Combination therapy with Flx + NI did not show any anxiogenic effects, while causing even higher expression levels of cFOS. In conclusion, addition of NI treatment to subchronic Flx therapy accelerated the abrogation of Flx's anxiogenic properties. Furthermore, hippocampal activity, as evidenced by cFOS expression, was biphasically related to anxiety-related behavior.

Protective Effects of Leukadherin1 in a Rat Model of Targeted Experimental Autoimmune Encephalomyelitis (EAE): Possible Role of P47phox and MDA Downregulation.

BACKGROUND: Reactive oxygen and nitrogen species (ROS and RNS) are involved in pathologic mechanisms underlying demyelination and exacerbation in multiple sclerosis (MS) lesions. P47phox is the most important subunit of an ROS-producing enzyme (NADPH oxidase) which is reportedly upregulated in MS plaques due to the intense activity of infiltrated immune cells and resident microglia. Leukadherin1 is a specific CD11b/CD18 agonist that inhibits signaling and transmigration of inflammatory cells to sites of injury. Based on this mechanism, we evaluated therapeutic effects of leukadherin1 in an animal model of targeted experimental autoimmune encephalomyelitis (EAE) through focal injection of inflammatory cytokines to the spinal cord. METHODS: For model induction, Lewis rats were first immunized with 15µg MOG 1-125 emulsion. Twenty days later, animals were subjected to stereotaxic injection of IFNγ and TNFα to the specific spinal area (T8). One day after injection, all animals presented EAE clinical signs, and their behaviors were monitored for eight days through open-field locomotion and grid-walking tests. Leukadherin1-treated animals received daily intraperitoneal injections of 1mg/kg of the drug. The specific spinal tissues were extracted on day 5 in order to measure nitric oxide (NO), malon di-aldehyde (MDA), and TNFα concentrations alongside P47phox real-time PCR analysis. In addition, spinal sections were prepared for immunohistochemical (IHC) observation of infiltrated leukocytes and activated microglia. RESULTS: Leukadherin1 exhibited promising improvements in EAE clinical scores and behavioral tests. Demyelination, CD45+ leukocyte infiltration, and Iba1+ microglia activation were reduced in spinal tissues of leukadherin1-treated animals. Furthermore, P47phox expression levels, MDA, and NO amounts were decreased in treated animals. However, TNFα concentrations did not differ following treatment. CONCLUSION: Based on our results, we suggest that leukadherin1 may be used as a novel therapeutic agent in tackling the clinical challenge of multiple sclerosis, especially during the acute phase of the disease. This effect was possibly mediated through decreased leukocyte infiltration and oxidative stress.