α-Mannosidosis: The first Turkish case

We describe a 10 month old boy with α-mannosidosis who presented with recurrent bronchopneumonia and diarrhea. Facial coarsening, deafness, hepatosplenomegaly, umbilical hernia, pectus carinatum and widespread Mongolian spots were distinguishing features. He also had mild skeletal deformities grouped together as ‘dysostosis multiplex’, and vacuolated lymphocytes on peripheral blood smear. These findings coupled with an abnormal urinary oligosaccharide pattern led to the suspicion of a lysosomal storage disease in the patient which proved to be α-mannosidosis. An exceptionally low level of α-mannosidase activity was subsequently found in serum and cultured skin fibroblasts. The patient's brother, who had died at the age of 10 months, had similar features. To the best of our knowledge, this is the first case reported from Turkey.     

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26–87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients’ performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78–7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79–6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12–2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.     

Effectiveness of a clinical practice intervention in early rheumatoid arthritis

Objective

To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics.

Methods

We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models.

Results

A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of ?0.24 (95% confidence interval [95% CI] ?0.39, ?0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of ?0.05 (95% CI ?0.09, ?0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes.

Conclusion

Preventing major radiographic progression in a 2‐year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup.

     

Cytotoxic effects of halogen- and light-emitting diode-cured compomers on human pulp fibroblasts

Objective.  The aim of this study was to determine the cytotoxic effects of three different compomers (Dyract AP, Compoglass, and Hytac) cured using a halogen light-curing unit (LCU) and a light-emitting diode (LED) LCU on human pulp fibroblasts.
Methods.  Specimens of three compomers were added to human pulp fibroblast cultures. Cytotoxicity was evaluated over 96 h using the agar overlay method.
Results.  All three compomers tested were found to be moderately cytotoxic to human pulp fibroblasts, regardless of whether they were cured using halogen or LED LCUs. The decolorization zone of Hytac was significantly larger than those of the other compomers tested ( P  < 0.05). Dyract AP and Compoglass specimens showed greater decolorization when cured with LED than with halogen LCUs ( P  < 0.05).
Conclusion.  Compomers are potentially toxic to human pulp fibroblasts, and the type of curing unit may affect compomer toxicity.     

Evaluation of sponging and antipyretic medication to reduce body temperature in febrile children

Two hundred and twenty-four children aged 6 months to 5 years, with rectal temperatures greater than or equal to 39°C (104°F), were randomly treated with sponging alone or with medication including a single oral dose of aspirin 15 mg/kg, or paracetamol 15 mg/kg, or ibuprofen 8 mg/kg. Twenty-three children were excluded from the final analysis because they did not complete the study. Demographic characteristics of the patients were found to be comparable in all groups. Rectal temperatures were recorded every 30 min for a 3 h period. During the first 30 min of intervention, sponging was found to be more effective than all of the three medications. After 60 min, the effects of each medication became superior to sponging with tepid water in reducing body temperature. Twenty-three children were excluded from the final analysis because they did not complete the study. Comparing the effect of the three different medications, it was seen that the antipyretic efficacy of aspirin and ibuprofen were significantly more than paracetamol 3 h after intervention (P < 0.05). For the management of fever over 39°C, it is therefore recommended to give children an antipyretic drug, preferably ibuprofen, and at the same time to begin sponging to provide a rapid and sustained antipyresis.     

circRNAs in drug resistance of breast cancer

Breast cancer (BC) is the most common heterogeneous disease in women and one of the leading causes of cancer-related death. Surgery, chemotherapy, radiotherapy, hormone, and targeted therapy are the gold standards for BC treatment. One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics, resistance that severely limits the use and effectiveness of the drugs used for BC treatment. Therefore, it is essential to develop new strategies to improve therapeutic efficacy. Circular RNAs (circRNAs) are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′, and 3′; ends. Accumulating evidence suggests that circRNAs have a vital role in cancer development, progression, and BC resistance to chemotherapy. The purpose of this review is to discuss the biological properties of circRNAs, and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment, by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance, such as drug efflux, apoptosis dysfunction, autophagy, and DNA damage repair. CircRNAs are associated with drug resistance via ATP-binding cassette (ABC) efflux transporters, while some others by inhibition of cell apoptosis, thus leading to resistance to tamoxifen in BC cells. In contrast, others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy. CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment. CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.     

Effect of urothelium on bladder contractility in diabetic rats

AIM: It is known that physiopathological changes in diabetes affect the function of the bladder. In this study, we aimed to demonstrate the possible effects of diabetes on the urothelium during this physiopathological process. METHODS: Diabetes was induced in rats by tail vein injection of 35 mg/kg streptozotocin. Eight weeks later, intact and denuded bladder strips were prepared from these rats. Electrical field stimulation (EFS; 0.5-32 Hz), carbachol (10(-8)-10(-3) mol/L; cumulative dosage-response curves) and KCl (120 mmol/L) were used for the evaluation of the contractile responses. All responses were expressed as mg tension developed per mg of bladder tissue. Weights of rats and of their bladders, blood glucose levels, and frequency- and concentration-response curves were compared using anova, the paired t-test and the independent t-test. Differences were considered significant at P<0.05. RESULTS: Although no differences related to the weight of bladders of the control and diabetic groups were observed, there were differences in blood glucose levels and body weights between the two groups. Similarly, although there were no differences between the data obtained with EFS and KCl from tissues with intact and denuded strips in the control group, carbachol responses significantly differed between intact and denuded strips in the non-diabetic group. These differences were not observed in the diabetic group. In the control groups, in the presence of additional strips with intact urothelium placed in the medium containing denuded tissue, the differences in contractile responses between the intact control strip and the denuded strip disappeared. CONCLUSIONS: Diabetes possibly changes the interaction between the relaxant factors that are released from urothelium and muscarinic stimulation, but these interactions are not completely understood yet. Consequently, the response of the bladder to contractile stimulants is also affected. Further studies are required to reveal the mechanism by which diabetes influences the urothelium.     

Effect of ascorbic acid treatment on endothelium-dependent and neurogenic relaxation of corpus cavernosum from middle-aged non-insulin dependent diabetic rats

AIMS: The purpose of the present study was to investigate functional responses and nitric oxide synthase activity in the corpus cavernosum of young control, middle-aged control and middle-aged non-insulin dependent diabetic rats. METHODS: The animal groups were treated with ascorbic acid. RESULTS: Acetylcholine-mediated endothelium-dependent relaxation of cavernosal tissue was significantly attenuated from a maximum of 58.0 +/- 4.1% (1 mmol, n = 10) in young rats to 44.3 +/- 1.6% in aged-matched controls (P < 0.05) and to 23.3 +/- 2.8% in non-insulin-dependent diabetes mellitus rats (P < 0.01). These deficits in acetylcholine responsiveness were completely prevented by ascorbic acid treatment. Non-adrenergic non-cholinergic relaxations evoked by electrical field stimulation (0.5-64.0 Hz) in the corpus cavernosum of middle-aged control and non-insulin dependent (NID) diabetic rats are blunted and were not restored by ascorbic acid. The histochemical findings demonstrated a decrease of nicotinamide adenine dinucleotide phosphate-diaphorase staining in the cavernosal tissue obtained from middle-aged control rats and middle-aged diabetic rats. CONCLUSION: Partial correction by ascorbic acid may suggest the importance of reactive oxygen species and a therapeutic approach in impotent NID diabetic men.