Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study.

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-ß, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Machine-learning-based predictions of imprinting quality using ensemble and non-linear regression algorithms.

The molecularly imprinted polymers are artificial polymers that, during the synthesis, create specific sites for a definite purpose. These polymers due to their characteristics such as stability, easy of synthesis, reproducibility, reusability, high accuracy, and selectivity have many applications. However, the variety of the functional monomers, templates, solvents, and synthesis conditions like pH, temperature, the rate of stirring, and time, limit the selectivity of imprinting. The Practical optimization of the synthetic conditions has many drawbacks, including chemical compound usage, equipment requirements, and time costs. The use of machine learning (ML) for the prediction of the imprinting factor (IF), which indicates the quality of imprinting is a very interesting idea to overcome these problems. The ML has many advantages, for example a lack of human error, high accuracy, high repeatability, and prediction of a large amount of data in the minimum time. In this research, ML was used to predict the IF using non-linear regression algorithms, including classification and regression tree, support vector regression, and k-nearest neighbors, and ensemble algorithms, like gradient boosting (GB), random forest, and extra trees. The data sets were obtained practically in the laboratory, and inputs, included pH, the type of the template, the type of the monomer, solvent, the distribution coefficient of the MIP (KMIP), and the distribution coefficient of the non-imprinted polymer (KNIP). The mutual information feature selection method was used to select the important features affecting the IF. The results showed that the GB algorithm had the best performance in predicting the IF, and using this algorithm, the maximum R2 value (R2 = 0.871), and the minimum mean absolute error (MAE = - 0.982), and mean square error were obtained (MSE = - 2.303).

A new approach to prediction riboflavin absorbance using imprinted polymer and ensemble machine learning algorithms.

The molecularly imprinted polymer (MIP) is useful for measuring the amount of riboflavin (vitamin B2), in various samples using UV/Vis instruments. The practical optimization of the MIP synthesis conditions has a number of drawbacks, like the need to spend money, the need to spend time, the use of the compounds that cause contamination, needing laboratory equipment and tools. Using machine learning (ML) to predict the amount of riboflavin absorbance is a creative solution to overcome the problems and shortcomings of optimizing polymer synthesis conditions. In fact, by using the model without needing real work in the laboratory, the optimum laboratory conditions are determined, and as a result the maximized absorption of the riboflavin is obtained. In this paper, MIP was synthesized for selective extraction of the riboflavin, and UV/Vis spectrophotometry was used to quantitatively measure riboflavin absorbance. Various factors affect the performance of the polymer. The effect of six important factors, including the molar ratio of the template, the molar ratio of monomer, the molar ratio of cross-linker, loading time, stirring rate, and pH, were investigated. Then, using ensemble ML algorithms, like gradient boosting (GB), extra trees (ET), random forest (RF), and Ada boost (Ada) algorithms, an accurate model was created to predict the riboflavin absorption. Also, the mutual information feature selection method was used to determine the important features. The results of using feature selection method was shown that variables such as the molar ratio of the template, the molar ratio of the monomer, and the molar ratio of the cross-linker had a high effect on riboflavin absorbance. The GB and Ada boost algorithms performed better than ET and RF algorithms. After tuning the n-estimator hyper parameter (n-estimator = 300), the GB algorithm was shown an excellent performance in predicting the absorbance of riboflavin and the maximum R2-scoring of the model was obtained at 0.965995, the minimum of the mean absolute error (MAE), and mean square error (MSE) of the model respectively were obtained -0.003711 and -0.000078. Therefore, by using the proposed model, it is possible to predict riboflavin absorbance theoretically, and with high accuracy by changing the inputs of model, and using the model instead of working in the lab saves time, money, chemical compounds, and lab ware.

The biological weapons threats and coping strategies for health promotion.

The biotechnology revolution and the emergence of new ways to change the genetic material of an organism have led to an increased risk of biological wars. Coping strategies against these threats is very important to improve the health of people. Therefore, due to the importance of this issue, this study is aimed to review the scope of using biotechnology and genetic engineering in wars and coping strategies in all over the world. In this review study, database includes of PubMed, Web of Science, Google Scholar, Scopus, and Science Direct were searched. The search was limited to reviewed articles in English published between 1990 and 2020. The primary search results generated 148 relevant references. After eliminating the duplicates and articles which were not related to the review of the abstract, 11 references were identified for inclusion in this review. Based on the results of these studies, the advances in genetic engineering can lead to the development of new weapons for other types of conflict and war scenarios, secret operations, and sabotage activities. Rapid developments in biotechnology and genetics have created environmental, ethical, political, and social challenges for many communities. Increasing awareness and sensitivity, monitoring, and building capacity for effective coping are essential. Biotechnology areas that will probably significantly contribute to countering biological weapons include recognizing the human genome, strengthening the immune system, identifying bacteria and viruses' genome, equipment for biological identification, new vaccines, new antibiotics, and anti-viral drugs must be monitored.

Reversible left bundle branch block should be mentioned in cardiac resynchronization therapy; A clinical case report.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a medical device to help cardiac synchronized contractility by electrical impulses. Improvement of symptoms and left ventricular systolic function, reducing hospital admissions and mortality in patients with moderate to severe heart failure are the main benefits of administration of cardiac resynchronization therapy. CASE REPORT: In this article, we describe a case of heart failure and left bundle branch block (LBBB) who was candidate for cardiac resynchronization therapy; but after managing hyperkalemia, left bundle branch block resolved, ejection fraction increased and cardiac resynchronization therapy implantation was canceled. CONCLUSION: Exclusion of treatable causes is the first important step before any interventions. Now there is an important question; is cardiac resynchronization therapy effective in patients with heart failure and transient or intermittent left bundle branch block?

Asymptomatic Interrupted Aortic Arch, Severe Tricuspid Regurgitation, and Bicuspid Aortic Valve in a 76-Year-Old Woman.

Interrupted aortic arch is a rare congenital abnormality with a high infancy mortality rate. The principal finding is loss of luminal continuity between the ascending and descending portions of the aorta. Because of the high mortality rate in infancy, interrupted aortic arch is very rare among adults. In this report, we describe the case of a 76-year-old woman with asymptomatic interrupted aortic arch, severe tricuspid regurgitation, and bicuspid aortic valve. To our knowledge, she is the oldest patient ever reported with this possibly unique combination of pathologic conditions. In addition to reporting her case, we review the relevant medical literature.

From Pulmonary Embolism to Inflammatory Bowel Disease; Give Tunnel Vision up.

Inflammatory bowel disease (IBD) is a multisystem disorder with gastrointestinal tract involvement. These patients have the higher risk for thromboembolic events compared to normal population. This report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease.

Intranasal desmopressin as an adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled, clinical trial.

Considering the role of neurohypophyseal peptides in normal development and function of higher cortical processes along with their proven abnormalities in schizophrenic patients, these pathways have recently attracted greater attention as treatment targets for schizophrenia. Desmopressin (DDAVP) is a synthetic analog of vasopressin. This study aimed to evaluate the efficacy and safety of DDAVP nasal spray as an adjunct to risperidone in improving negative symptoms of schizophrenia. In this randomized double-blind placebo-controlled clinical trial, forty patients aged 18-50 years with a DSM IV-TR diagnosis of chronic schizophrenia and a minimum score of 60 on positive and negative syndrome scale (PANSS) were equally randomized to receive DDAVP nasal spray (20mcg/day) or placebo in addition to risperidone for 8 weeks. Patients were partially stabilized and treated with a stable dose of risperidone (5 or 6mg/day) for at least four weeks prior to entry. Participants were rated by PANSS every two weeks and decrease in the PANSS negative subscale score was considered as our primary outcome. By the study endpoint, DDAVP-treated patients showed significantly greater improvement in the negative symptoms (P=0.001) as well as the PANSS total and general psychopathology subscale scores (P=0.005 and P=0.003; respectively) compared to the placebo group. Treatment group was the strongest predictor of changes in negative symptoms (ß=-0.48, t=-3.67, P=001). No serious adverse event or fluid/electrolyte imbalance was reported in this trial. In conclusion, DDAVP nasal spray showed to be an effective and safe medication for improving negative symptoms in patients with chronic schizophrenia.

Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P<0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P<0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (ß=-0.94, t=-10.59, P<0.001) followed by the change in PANSS positive subscale (ß=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia.

A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia.

RATIONALE: Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies. OBJECTIVES: We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia. METHODS: In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups. RESULTS: By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P < 0.001) as well as the PANSS total and general psychopathology subscale scores (P = 0.001 and P < 0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (ß = -0.56, P < 0.001). No significant difference was observed between two groups in the frequency of side effects. CONCLUSION: These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted. Clinical trial registry name and registration number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26

N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Despite the burden of negative symptoms on quality of life in schizophrenic patients, no completely effective treatment has been developed to address such symptoms yet. Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia, and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia. N-Acetylcysteine (NAC) is a potent antioxidant with neuroprotective properties. This study aimed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. The participants were equally randomized to receive NAC (up to 2 g/d) or placebo, in addition to risperidone (up to 6 mg/d) for 8 weeks. The participants were rated using PANSS every 2 weeks, and the decrease of PANSS negative subscale score was considered as our primary outcome. RESULTS: By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total (P = 0.006) and negative subscale (P < 0.001) scores than that in the placebo group, but this difference was not significant for positive and general psychopathology subscales. There was no significant difference between the 2 groups in the frequency of adverse effects. CONCLUSIONS: NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia.

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia.

RATIONAL: A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia. METHODS: In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8. RESULTS: Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699) = 37.366, p < 0.001] as well as negative scores [F(2.439,92.675) = 16.623, p < 0.001] and general psychopathology [F(1.767,67.158) = 4.602, p = 0.017], but not positive subscale scores [F(1.348, 51.218) = 0.048, p = 0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized ß = -0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups. CONCLUSION: Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.

Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Several small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. STUDY DESIGN: This was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. STUDY SETTING: The study setting was outpatient clinics of two large referral centres. PATIENTS: Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21. INTERVENTIONS: Participants were randomly assigned to granisetron (Kytril(®); SmithKline Beecham, Philadelphia, PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks. MAIN OUTCOME MEASURE: Patients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups. RESULTS: Of the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and compulsion (F [2.050, 77.899] = 4.674, p = 0.012) subscales. By week 8, complete response and remission were achieved by 20 (100%) and 18 (90%) patients in the granisetron group and by 7 (35%) patients in the placebo group (p-value of Fisher's exact test <0.001, risk ratio (RR) [95% CI] = 3.857 [2.039, 7.297]). There was no significant difference in the tolerability between the two regimens. CONCLUSION: Granisetron is an efficacious adjunct for the short-term treatment of patients with moderate to severe OCD and is well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: IRCT201202041556N32.

Should we think of Urbach-Wiethe disease in refractory epilepsy? Case report and review of the literature.

Urbach-Wiethe disease (UWD) is an autosomal recessive disease characterized by both neurological and dermatological manifestations. Face specially eyelids are commonly involved. Alopecia, nail dystrophy and dental anomalies have been reported as less frequent symptoms. Some patients show evidences of epilepsy and psychiatric symptoms such as schizophrenia, mood disorders, and anxiety due to calcium deposits in different parts of the brain. In this report, we describe the case of a young woman affected by UWD presenting with neurological involvements and no dermatological manifestations. This patient is a unique case of UWD as she has partial seizures and hoarseness. Also we summarize relevant data from the literature.