Criticality and universality in neuronal cultures during "up" and "down" states.

The brain can be seen as a self-organized dynamical system that optimizes information processing and storage capabilities. This is supported by studies across scales, from small neuronal assemblies to the whole brain, where neuronal activity exhibits features typically associated with phase transitions in statistical physics. Such a critical state is characterized by the emergence of scale-free statistics as captured, for example, by the sizes and durations of activity avalanches corresponding to a cascading process of information flow. Another phenomenon observed during sleep, under anesthesia, and in in vitro cultures, is that cortical and hippocampal neuronal networks alternate between "up" and "down" states characterized by very distinct firing rates. Previous theoretical work has been able to relate these two concepts and proposed that only up states are critical whereas down states are subcritical, also indicating that the brain spontaneously transitions between the two. Using high-speed high-resolution calcium imaging recordings of neuronal cultures, we test this hypothesis here by analyzing the neuronal avalanche statistics in populations of thousands of neurons during "up" and "down" states separately. We find that both "up" and "down" states can exhibit scale-free behavior when taking into account their intrinsic time scales. In particular, the statistical signature of "down" states is indistinguishable from those observed previously in cultures without "up" states. We show that such behavior can not be explained by network models of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression, even when realistic noise levels, spatial network embeddings, and heterogeneous populations are taken into account, which instead exhibits behavior consistent with previous theoretical models. Similar differences were also observed when taking into consideration finite-size scaling effects, suggesting that the intrinsic dynamics and self-organization mechanisms of these cultures might be more complex than previously thought. In particular, our findings point to the existence of different mechanisms of neuronal communication, with different time scales, acting during either high-activity or low-activity states, potentially requiring different plasticity mechanisms.

The burden of atrial fibrillation/flutter in the Middle East and North Africa region and its associated risk factors from 1990 to 2019.

BACKGROUND: Atrial fibrillation and flutter (AFF) are the most common cardiac arrhythmias globally, contributing to substantial morbidity and mortality. The Middle East and North Africa (MENA) region face unique challenges in managing cardiovascular diseases, including AFF, due to diverse sociodemographic factors and healthcare infrastructure variability. This study aims to comprehensively evaluate the burden of AFF in MENA from 1990 to 2019. METHODS: Data were obtained from the Global Burden of Diseases Study 2019, a comprehensive source incorporating diverse data inputs. The study collected global, regional, and national Age-Standardized Incidence Rate (ASIR), Age-Standardized Mortality Rate (ASMR), and Age-Standardized Disability-Adjusted Rate (ASDR), Mortality across sex, age groups, and years. LOESS regression was employed to determine the relationship between age-standardized rates attributed to AFF and Socio-Demographic Index (SDI). RESULTS: The study found minimal change in ASIR of AFF in MENA from 1990 to 2019, with a slight increase observed in ASMR and ASDR during the same period. Notably, AFF burden was consistently higher in females compared to males, with age showing a direct positive relationship with AFF burden. Iraq, Iran, and Turkey exhibited the highest ASIR, while Qatar, Bahrain, and Oman had the highest ASMR and ASDR in 2019. Conversely, Kuwait, Libya, and Turkey displayed the lowest ASMR and ASDR rates. CONCLUSION: This study underscores the persistent burden of AFF in MENA and identifies significant disparities across countries. High systolic blood pressure emerged as a prominent risk factor for mortality in AFF patients. Findings provide crucial insights for policy-making efforts, resource allocation, and intervention strategies aimed at reducing the burden of cardiovascular diseases in the MENA region.

Gastric bypass surgery in morbid obesity: Influence on thyroid function tests and insulin resistance status.

Background: There are inconsistent results about the effect of gastric bypass surgery on thyroid function tests in morbidly obese subjects. The aim of this study was to investigate the changes in thyroid function tests and insulin resistance status in euthyroid morbidly obese subjects before and three months after gastric bypass surgery (GBS). Methods: Twenty-nine subjects with morbid obesity (BMI≥40) were enrolled in this before-after study. Patients with known thyroid disorders or a history of thyroid ablative therapy, users of drugs that affect thyroid function, or fasting blood sugar and insulin were excluded. TSH, Free T4, total T3, fasting blood sugar and insulin level, and BMI were measured before and 3 months after GBS. Statistical analysis was performed with appropriate tests and p<0.05 was considered significant. Results: Body mass index (BMI), insulin sensitivity index (HOMA-IR), and total T3 significantly decreased after bypass surgery (all with p<0.001) but no significant changes were seen in TSH (P=0.203) and FreeT4 (P=0.33). There was a significant negative correlation between changes in HOMA-IR and changes in FreeT4 (P=0.038, r= -0.38). There was no statistically significant correlation between the percentage of excess BMI loss (%EBMIL) and changes in T3 (P=0.66), Free T4 (P=0.92), TSH (P= 0.27), and HOMA-IR (P=0.17). Conclusion: Although significant changes can occur in BMI, insulin sensitivity index, fasting blood sugar, and T3 in short-time follow-up after bariatric surgery, significant TSH and FreeT4 changes may need longer follow-ups.

Preoperative Vitamin.D Status and Post-Total Thyroidectomy Hypocalcemia.

Introduction: Hypocalcemia is a common complication of total thyroidectomy (TT). This study was designed to investigate the effect of preoperative vitamin.D (Vit.D) status on the occurrence of post-total thyroidectomy hypocalcemia. Materials and Methods: Patients who underwent TT without parathyroidectomy were divided into three groups based on their preoperative Serum Vit.D levels (<20 ng/ml, 20-30 ng/ml, and ≥30 ng/ml were considered deficient, insufficient, and normal Vit.D levels, respectively). Serum levels of calcium and phosphorus were measured before and 24 hours after surgery in all patients. The patients were examined for clinical symptoms and signs of hypocalcemia postoperatively. In cases with positive clinical symptoms and signs of hypocalcemia and/or calcium levels <8 mg/dl, PTH level was measured before starting calcium infusion, while serum calcium and phosphorus levels were also measured 24 hours later. Results: Among 100 patients enrolled in this study, 81% were females. The mean age was 36.60±8.32 years. Before surgery, the mean Vit.D level was 26.9±16.89 ng/ml, while 47% of cases had normal Vit.D level, 32% had insufficient vitamin levels, and 21% had Vit.D deficiency. Twenty-four hours after surgery, the calcium (P=0.356) and phosphorus (P=0.743) levels were not significantly different between the three Vit.D groups. A comparison of postoperative PTH levels between the three Vit.D groups showed no significant difference (P=0.596). Conclusions: Based on our findings, preoperative serum Vit.D levels did not affect postoperative serum calcium levels.

The Prognostic Role of Corticosteroid Administration in Hospitalized Patients with Severe COVID-19: A Cross-sectional Study.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic is a recent global issue with no established consensus on treatments. Therefore, the aim of this study was to assess the impact of corticosteroid (CS) pulses on the prognosis of COVID-19 patients admitted to hospitals. METHODS: In this retrospective single-center cross-sectional study, we used hospital records of all consecutive patients aged 18 years or older admitted to the hospital from July 23rd to September 23rd, 2021. All patients included in the study had confirmed SARS-CoV-2 infection using polymerase chain reaction (PCR) testing and required hospitalization. Demographic and clinical information, as well as patient outcomes, were collected. Treatment details, including the type(s), cumulative doses, and duration of administered corticosteroids, were also recorded. CS pulse therapy was defined as the daily administration of 24 mg or more of dexamethasone or its equivalents. RESULTS: A total of 500 patients with COVID-19 were included in this study, comprising 122 patients who received CS pulse therapy and 378 patients who did not. A higher mortality rate was observed in patients receiving CS pulse therapy (42.6%) compared to the other group (28%) (p =0.04). Additionally, logistic regression analysis showed an increased mortality risk in patients receiving CS pulse therapy in the crude model (OR=1.54, 95% CI: 1.01-2.27, p <0.01). However, after adjusting for confounding factors, such as mechanical ventilation and ICU admission, the results were reversed (OR=0.21, 95% CI: 0.07-0.62, p <0.01). ; Conclusion: In the findings of the current study, treatment with CS pulses was shown to significantly enhance recovery in patients with non-severe COVID-19.

Association of Metabolic Syndrome and Hyperuricemia in the Recipients of Kidney Transplants: A Single-Center Study.

INTRODUCTION: The prevalence of hyperuricemia shows an increasing trend among kidney transplant recipients. The association between metabolic syndrome and hyperuricemia among the recipients of kidney transplants may consequently lead to reduction in graft survival. In this regard, the present study aimed at comparing the kidney transplant recipients with and without metabolic syndrome in terms of the prevalence of hyperuricemia. METHODS: This cross-sectional study was carried out on kidney transplant recipients who were referred to the Kidney Transplant Clinic of Montaserieh Organ Transplant Hospital, Mashhad University of Medical Sciences, from 2019 to 2020. The serum uric acid, anthropometric data, renal function, glucose levels, and lipid profile of the study participants were evaluated. RESULTS: According to our findings, higher mean uric acid levels were reported in recipients with metabolic syndrome (6.9 ± 1.51 mg/dL), compared to recipients without metabolic syndrome (6.11 ± 1.47 mg/dL; P < .001). It was also found that 55.6 and 38.5% of the cases with and without metabolic syndrome had hyperuricemia, respectively (P < .05). Additionally, the results showed no significant association between hyperuricemia and the number of metabolic syndrome criteria (P > .05). A comparison between recipients with and without hyperuricemia revealed significantly lower levels of tacrolimus in the hyperuricemia group (P < .05). Regarding serum Tacrolimus levels, no significant difference was found between recipients with and without metabolic syndrome (P > .05). Moreover, there was no significant difference between recipients with and without hyperuricemia (P > .05) or metabolic syndrome (P > .05) in terms of serum cyclosporine level. CONCLUSION: The findings of the current study indicate that kidney transplant recipients suffering from metabolic syndrome have higher mean serum levels of uric acid than those without metabolic syndrome.  DOI: 10.52547/ijkd.7141.

Association between vitamin D status and risk of covid-19 in-hospital mortality: A systematic review and meta-analysis of observational studies.

Some earlier studies reported higher risk of COVID-19 mortality in patients with vitamin D deficiency, while some others failed to find such as association. Due to inconsistences between earlier meta-analyses and needs for an updated study, we conducted current systematic review and meta-analysis on the association between vitamin D status and risk of COVID-19 in-hospital mortality among observational studies. We searched PubMed, Scopus and Web of Science up to 27 July 2021. We conduct our systematic review and meta-analysis in according to PRISM statement. Two authors independently screened studies and extracted data from the relevant ones. All types of observational studies about the association between vitamin D status and in hospital COVID-19 mortality were included. Data was pooled using a random-effect model. P-values ˂ 0.05 was assumed as statistically significant. We identified 13 observational studies. Pooling 9 studies which categorized vitamin D level, a significant positive relationship was found between vitamin D deficiency and risk of COVID-19 in-hospital mortality (Odds Ratio (OR): 2.11; 95% Confidence Interval (CI): 1.03, 4.32). All subgroup analyses also showed significant relationship between vitamin D deficiency and risk of COVID-19 in-hospital mortality. In the other analysis, pooling data from 5 studies in which vitamin D level was entered as a continues variable, we found an inverse significant association between each unit increment in serum vitamin D concentrations and risk of COVID-19 in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99). We found a significant direct association between vitamin D deficiency and elevated risk of COVID-19 in-hospital mortality. Moreover, each unit increment in serum vitamin D levels was associated to significant reduction in risk of COVID-19 mortality. Further prospective studies are needed to confirm our findings.

Accuracy of fine-needle aspiration cytopathology to differentiate malignant and benign thyroid nodules with ≥4 cm diameter: A retrospective study.

BACKGROUND: Thyroid nodules (TN) are commonly present in the general population and are usually pathologically benign. An initial diagnosis with fine-needle aspiration (FNA) cytopathology could help clinical decision-making with fewer complications. As the previous studies suggest surgical procedures for >4 cm TNs, we aimed to investigate the accuracy of preoperative FNA cytology to predict malignancy risk in these nodules in a sample of the Iranian population. METHODS: Patients with ≥4 cm TNs who had preoperative FNA cytology, underwent nodulectomy and had a histopathological report were included. Each patient's preoperative demographic, ultrasonographic, and cytology data were gathered. After surgery, resected samples were assessed pathologically and diagnosed as benign or malignant. Finally, data were analyzed to evaluate the presurgical accuracy of the FNA cytology. RESULTS: We identified 41 (51.25%) patients with malignant legions among our study population (N = 80). The pathology reports were indeterminate in 3 patients with follicular neoplasm. Bethesda scores were substantially higher in patients with malignancy. The sensitivity, specificity, and false-negative rate of FNA cytology reports using the Bethesda system were 73.7%, 74.2%, and 26.3%, respectively. There was no association between malignancy and TNs' size, neither their volume nor their highest diameter. CONCLUSION: FNA cytology is not as sensitive and specific in nodules>4 cm as in smaller ones. However, it can still be used alongside other diagnostic procedures in malignancy screening. Clinicians should make more complex decisions considering various influential factors to avoid missing malignant lesions and reduce diverse probable complications of highly invasive diagnostic surgery. Further prospective research on >4 cm TNs and their multiple features' association with malignancy is required for more precise judgment.

Xanthogranulomatous hypophysitis: A rare presentation in a young female patient.

Hypophysitis is a rare inflammatory condition that may present both clinically and radiologically as a neoplastic lesion. Xanthogranulomas are rare intracranial lesions with controversial etiology. Here, we report a clinical case of histologically confirmed xanthogranulomatosis hypophysitis in a young female with type I diabetes mellitus and hypothyroidism.

The Prognostic Role of Metabolic and Endocrine Parameters for the Clinical Severity of COVID-19.

OBJECTIVE: An outbreak of coronavirus disease-19 (COVID-19) began in December 2019 and spread globally, overwhelming the entire world. COVID-19 is a public health emergency of international concern. Due to its high morbidity and mortality rate, recognition of its risk and prognostic factors is important. We aimed to understand the relationship between metabolic and endocrine parameters and the prognosis of COVID-19. METHODS AND MATERIALS: This was a cross-sectional clinical study. A total of 70 patients with severe COVID-19 were enrolled. Laboratory results at the first admission time (including complete blood count, C-reactive protein, lactate dehydrogenase, blood glucose, calcium, phosphate, albumin, creatinine, magnesium, lipid profiles, liver enzymes, thyroid hormones, cortisol, and vitamin D) and outcome data were recorded. We divided patients into (1) intensive care unit- (ICU-) admitted and non-ICU-admitted and (2) survivors and nonsurvivors for estimation of severity and prognosis. We determined the risk factors associated with critical illness and poor prognosis. RESULTS: Patients with higher white blood cell (WBC) count and phosphate levels had significantly higher ICU admission rates. According to univariate analysis, serum levels of T3, phosphate, and WBC as well as the duration of hospitalization were associated with mortality. Multivariate analysis revealed that only WBC and duration of hospitalization were independent predictors for mortality rate in COVID-19 patients. CONCLUSION: Our findings suggest that longer duration of hospitalization and higher WBC count are associated with poor outcomes in patients with COVID-19.

The Effect of Levothyroxine in Comparison with Placebo on Serum Osteocalcin Levels in Patients with Subclinical Hypothyroidism.

BACKGROUND AND OBJECTIVE: Subclinical hypothyroidism can potentially develop into overt hypothyroidism. Thyroid hormones have substantial roles in metabolism and glucose homeostasis and thus, are closely related to determinant factors of metabolic syndromes, such as obesity and insulin resistance. Osteocalcin is considered a predictor of metabolic conditions in thyroid diseases. This study aimed to investigate the effect of levothyroxine vs. placebo on serum osteocalcin levels in patients with subclinical hypothyroidism. METHODS: This randomized clinical trial was performed on 30 patients with subclinical hypothyroidism, who were referred to the endocrine clinics of Ghaem and Imam Reza hospitals in Mashhad, Iran. After giving informed consent, patients were randomly divided into intervention (50 µg/- day levothyroxine for 2 months) and control (placebo) groups. Serum levels of osteocalcin, thyroid hormones, lipid profile, insulin, and fasting glucose, as well as other clinical and anthropometric data, were measured at baseline and at the end of the study. SPSS was used to analyze the data, and p < 0.05 was considered significant. RESULTS: Mean age in the intervention and control groups was 35.07 ± 9.94 and 31.30 ± 4.30, respectively (p = 0.20). There was no significant difference between osteocalcin levels before and after the intervention in either of the groups (p = 0.54). TSH level was significantly decreased in the levothyroxine group after the intervention (p < 0.01). T4 level was significantly increased in the intervention group (p = 0.02). CONCLUSION: Levothyroxine had no significant effect on the increasing levels of serum osteocalcin in patients with subclinical hypothyroidism.

Methadone associated long term hearing loss and nephrotoxicity; a case report and literature review.

BACKGROUND: Methadone is a long-acting opioid receptor agonist. Reported adverse effects of methadone include constipation, respiratory depression, dizziness, nausea, vomiting, itching, sweating, rhabdomyolysis, QT prolongation, and orthostatic hypotension. Hearing loss has been rarely reported following methadone use, and when reported, long term follow-up is rare. Herein we report a case of methadone poisoning with rhabdomyolysis, acute kidney injury, and persistent hearing loss documented by a 2 year follow up. CASE PRESENTATION: The patient was a 34 years old male who presented with a reduced level of consciousness and acute hearing loss after suicidal ingestion of 40 mg of methadone while experiencing family-related stresses. He had no prior history of methadone use, abuse, or addiction. Initial laboratory testing was significant for a serum creatinine concentration of 4.1 mg/dl, a mixed metabolic and respiratory acidosis, thrombocytopenia, abnormal hepatic transaminases, and coagulation tests. The patient then developed severe rhabdomyolysis. Also, audiometry showed a bilateral sensorineural hearing loss. The patient required hemodialysis for 11 days while his metabolic abnormalities gradually resolved. However, his hearing loss was persistent, as demonstrated by 2 years of follow up. CONCLUSION: Our patient simultaneously had kidney failure, rhabdomyolysis, and permanent hearing loss following methadone poisoning. Although rare, ototoxicity and permanent hearing loss may happen in cases of methadone poisoning. While opioid-induced hearing loss is uncommon, methadone toxicity should be taken into account for any previously healthy patient presenting with acute hearing loss with or without rhabdomyolysis.

Vitamin D deficiency and its associated risk factors in normal adult population of Birjand, Iran.

BACKGROUND: Vitamin D is required for calcium absorption, bone growth, and regulation of the immune system. Geographical location determines the intensity of the solar ultraviolet (UV) light as a significant determinant of vitamin D status in the many studies. This study was conducted to determine the status of vitamin D deficiency and its associated factors in adults of Birjand city, Iran (latitude: 32.87; longitude: 59.22). METHODS: This descriptive-analytic study was performed by random stratified sampling on 400 subjects over 40 years of age in Birjand, who signed the consent form for participation. Data were collected in winter within one month from eight municipal health centers. Information regarding demographic characteristics, blood pressure, and anthropometric indices were collected, and blood samples were collected to measure 25-hydroxyvitamin D concentration. RESULTS: The mean serum concentration of 25-OHD was 45.4 nmol/L. Twenty-six percent of subjects had vitamin D deficiency, 45.2% had insufficiency, and 28.8% of the subjects were healthy. The results of the multiple logistic regression showed that age (OR: 0.92, 95% CI = 0.89-0.96) and serum calcium concentration (OR: 0.52, 95% CI = 0.28-0.94) had a significant correlation with 25-OHD deficiency. CONCLUSION: A high percentage of adults in the city of Birjand are suffering from vitamin D deficiency, which implies a need for extensive training and food enrichment programs, promoting healthy lifestyles, and exercise and walking.

Cardiogenic Shock Due to Aluminum Phosphide Poisoning Treated with Intra-aortic Balloon Pump: A Report of Two Cases.

The mortality rate from aluminum phosphide (AlP) poisoning is as high as 70-100%, with refractory hypotension and severe metabolic acidosis being the two most common presentations in this poisoning. As this poisoning has no specific antidote, treatments revolve around supportive care. Cardiogenic shock created by toxic myocarditis is considered the main cause of mortality in these patients. Meanwhile, the intra-aortic balloon pump (IABP) has been suggested for the treatment of cardiogenic shock. This article reports the successful treatment of cardiogenic shock caused by AlP poisoning in a 17-year-old man and a 21-year-old woman using the IABP procedure.

The association between serum irisin levels and cardiovascular disease in diabetic patients.

BACKGROUND: Cardiovascular disease is the most common cause of mortality and morbidity in diabetic patients. Insulin resistance has been shown to be reduced by the secretion of irisin from muscle and adipose tissues. This study was aimed at determining the relationship between serum irisin levels and angiographically defined coronary artery disease (CAD) in type II diabetic patients. METHODS: In this case-control study, 30 diabetic subjects with angiographically defined CAD were compared with 30 age- and sex-matched diabetic subjects without CAD in terms of clinical and laboratory parameters including serum irisin levels. RESULTS: Serum levels of Irisin were significantly higher in the diabetic group without CAD compared with the group with CAD (P = 0.048). Serum irisin levels showed a significant positive correlation with BMI (r = 0.374, P = 0.004) and fasting insulin (r = 0.303, P = 0.021), and a significant negative correlation with diabetes duration (r = -0.384, P = 0.002). Based on the results of the binary logistic regression model, circulating levels of irisin were associated with the presence of CAD in diabetes (p = 0.038) after adjusting for potential confounders. CONCLUSION: Serum irisin levels were lower in the diabetic patients with cardiovascular complication compared with the uncomplicated diabetic patients. Therefore, additional larger scale studies are needed to determine the role of irisin in monitoring CAD in diabetic patients.

The efficacy of metformin compared with insulin in regulating blood glucose levels during gestational diabetes mellitus: A randomized clinical trial.

BACKGROUND: Insulin has been a conventional medication in the treatment of female patients suffering from gestational diabetes mellitus (GDM). However, the need for a large number of insulin injections in these patients causes them a lot of discomforts. Recently, an alternative medication, metformin, has received considerable attention in the treatment of GDM. The aim of this study was to compare the efficacy of metformin and insulin in regulating blood glucose levels and fetal outcomes in GDM. METHODS: This randomized clinical trial included 286 pregnant women diagnosed with positive GDM at 24-28 weeks of pregnancy. The subjects were randomly divided into two groups of 143 patients, with one group receiving insulin and the other undergoing a treatment plan using metformin. Fasting plasma glucose (FPG), 2-hr plasma glucose (PG) and glycated hemoglobin (HbA1c) were recorded twice a month until delivery. Other variables, including birth delivery method, cause of cesarean section, gestational age at the delivery time, birth trauma, Apgar score, birth weight, admission at neonatal intensive care unit (NICU), and neonatal hypoglycemia were also registered. RESULTS: Age of mother, body mass index, history of diabetes in the family, previous history of GDM, parity, FPG, 1- and 2-hr PG after meals, and 75-g glucose tolerance test before treatment were not statistically different between the two groups. FPG, PG, and HbA1c did not show significant differences between the two groups after completing the course of treatment. There was also no significant difference between two groups regarding the birth delivery method, the cause of cesarean section, birth trauma, Apgar score, birth weight, admission at NICU, and neonatal hypoglycemia. CONCLUSION: As mean FPG and 2-hr PG were not significantly different between the two groups, it seems that metformin can be recommended as an effective substitute for insulin in the treatment of GDM. However, there are still some undesirable risk factors with both treatments that may threaten the mother and the newborn.

Neuronal avalanche dynamics indicates different universality classes in neuronal cultures.

Neuronal avalanches have become an ubiquitous tool to describe the activity of large neuronal assemblies. The emergence of scale-free statistics with well-defined exponents has led to the belief that the brain might operate near a critical point. Yet not much is known in terms of how the different exponents arise or how robust they are. Using calcium imaging recordings of dissociated neuronal cultures we show that the exponents are not universal, and that significantly different exponents arise with different culture preparations, leading to the existence of different universality classes. Naturally developing cultures show avalanche statistics consistent with those of a mean-field branching process, however, cultures grown in the presence of folic acid metabolites appear to be in a distinct universality class with significantly different critical exponents. Given the increased synaptic density and number of feedback loops in folate reared cultures, our results suggest that network topology plays a leading role in shaping the avalanche dynamics. We also show that for both types of cultures pronounced correlations exist in the sizes of neuronal avalanches indicating size clustering, being much stronger in folate reared cultures.

Topical propolis improves wound healing in patients with diabetic foot ulcer: a randomized controlled trial.

In this randomized controlled trial, diabetic patients with foot ulcers (Wagner grades 1 and 2) were randomly assigned to conventional therapies for diabetic foot ulcer plus topical propolis ointment (5%; twice daily) or conventional therapies alone. The process of ulcer healing was observed during 4 weeks and compared between the two groups regarding the size, erythema, exudates, white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). The process of ulcer size reduction during the four-week period of study was significantly different between the groups. However, this difference was not significant between the third and fourth weeks. There was no significant difference between two groups regarding erythema and exudate reduction as well as WBC count and ESR. Administration of topical propolis ointment in addition to the conventional treatments of diabetic foot ulcer could reduce the size of ulcers with Wagner grades 1 and 2.

The relationship between serum levels of fibroblast growth factor 21 and diabetic retinopathy.

Fibroblast growth factor 21 (FGF21) is a major metabolic regulator that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome, but few studies about the relationship between serum FGF21 and the complications of diabetes have been done. Since the association between FGF21 and diabetic retinopathy is not clear, this study was conducted to investigate this relationship. In this cross-sectional study, 61 subjects (14 healthy controls, 22 diabetic patients without retinopathy, and 25 patients with diabetic retinopathy) were evaluated. All patients in the study were examined for the presence of diabetic retinopathy. Various clinical and biochemical parameters including FGF21 were evaluated and analyzed and compared between the study groups. Serum levels of FGF21 showed a significant difference between the three groups (P=0.003) but the difference between diabetic patients with and without retinopathy was not significant (P=0.122). Regression model was used to evaluate the role of FGF21 in predicting diabetic retinopathy. In the multivariate logistic regression model after adjustment of systolic blood pressure and fasting blood glucose, the level of FGF21 was not associated with diabetic retinopathy. In the multivariate model, only fasting blood glucose was associated with diabetic retinopathy (P=0.009). According to the results of this study, serum levels of FGF21 in diabetic patients was higher than the control group but these raised levels could not predict the presence of diabetic retinopathy.

Comparison of ex vivo harvested and in vitro cultured materials from Echinococcus granulosus by measuring expression levels of five genes putatively involved in the development and maturation of adult worms.

Parts of the natural life cycle of Echinococcus granulosus can be retraced in vitro such as the development of protoscoleces into semiadult worms with three or more proglottids, or the redifferentiation of in vitro cultured protoscoleces into metacestode-like cystic structures. Most in vitro generated samples share-at the microscopical level-high similarities with those naturally grown, but developmental differences have also been documented, such as missing egg production in in vitro grown adults or unusual bladder/vesicle formation in protoscoleces cultured into the metacestode direction. The aim of the present study was to explore how far different in vitro generated stage-specific materials/structures match the natural situation on the transcriptome level, based on testing five exemplarily chosen different genes: the frizzled receptor eg-fz4 (posterior marker), the FGF receptor-like factor eg-fgfrl (anterior association), the cell differentiation protein eg-rcd1 (part of the CCR4-NOT complex, a key regulator of eukaryotic gene expression), the rapidly accelerated fibrosarcoma serin/threonin kinase eg-braf (part of the MAPK pathway involved, e.g., in EGF signaling) and the co-smad eg-smadD (downstream factor of TGFß/BMP2/activin signaling). These genes-tested via qPCR-were selected such as to allow a discussion on their potential role in the development of E. granulosus into the adult stage. Thus, testing took place with three ex vivo isolated samples, namely (i) egg-containing adult worms, (ii) invaginated protoscoleces, and (iii) protoscolex-free germinal layer tissue. Respective data were compared (a) with in vitro generated metacestode-like microcysts developed from protoscolices, and (b) different development stages of protoscoleces in vitro cultured toward adult maturation. As a finding, only eg-smadD and partially eg-fz4 showed high expression similarities between ex vivo harvested and in vitro cultured E. granulosus, thus suggesting a putative role in adult maturation. Conclusively, the fact of using "only" five genes did not allow answering the question if ex vivo and in vitro materials are similar on the transcriptome level. Another experimental restriction arises from different growth conditions of the in vitro cultured materials, and comparing these to the ex vivo harvested ones. Future experiments may solve the problems by using fully standardized E. granulosus sample collection and fully standardized culture conditions.