Effect of Aerobic/Strength Training on RANKL Gene DNA Methylation Levels.

BACKGROUND: The osteoclastogenesis RANKL gene plays a key role in bone remodeling. The hypomethylation of its promoter region may cause osteoporosis. The present study aimed to elucidate the influence of physical activity on DNA methylation changes of RANKL promoter cytosine-phosphate-guanine (CpG)-rich region in active and sedentary adults and to assess the effect of aerobic and strength training on RANKL DNA methylation changes among Tunisian-North African adults. METHODS: A total of 104 participants including 52 adults (58% males and 42% females) and 52 adults (31% males and 69% females) were recruited for the observational and interventional part of the study, respectively. The intervention consisted of 12 weeks of aerobic training (30 min/session) followed by 10 minutes of strengthening exercises. All participants completed the International Physical Activity Questionnaire and provided blood samples for quantitative methylation-specific polymerase chain reaction (PCR) analysis. RESULTS: The study revealed a significant difference (P = 6 × 10-10) in the methylation level of the RANKL promoter region between active and sedentary adults, with a 6.68-fold increase observed in the active group. After the intervention, both the trained (P = 41 × 10-5) and untrained (P = .002) groups displayed high methylation levels in the RANKL promoter region. In addition, the trained group exhibited significant improvements in heart rate (P = 2.2 × 10-16), blood pressure (P = 39 × 10-3), maximal oxygen uptake (P = 1.5 × 10-7), and fat mass (P = 7 × 10-4). CONCLUSION: Exploring epigenetic modifications in the RANKL promoter region may contribute to a more comprehensive understanding of the complexity of osteoporosis. This suggests that aerobic/strength training could potentially improve the bone system, reducing its vulnerability to osteoporosis by increasing RANKL DNA methylation.

A novel WFS1 variant associated with severe diabetic retinopathy in Wolfram syndrome type 1.

BACKGROUND: Wolfram syndrome type 1 is a rare neurodegenerative disorder including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, with variable additional findings. The phenotypic spectrum is very heterogeneous, with non-autoimmune juvenile-onset diabetes and optic atrophy as minimal criteria for the diagnosis. Biallelic mutations in the WFS1 gene are the causative genetic anomaly for the syndrome, with, however, no evident genotype-phenotype correlation. Among the clinical features of the disease, diabetic retinopathy depicts a rarely reported microvascular complication. In this report, we describe the clinical and genetic findings in a 26-year-old patient presenting with Wolfram syndrome and severe diabetic retinopathy. METHODS: The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the WFS1 gene. RESULTS: A novel homozygous missense variant c.1901A>T (p.Lys634Met) was found in the proband and classified as probably pathogenic according to the American College of Medical Genetics and Genomics. CONCLUSIONS: The molecular study of the WFS1 gene is essential for the diagnostic confirmation, to provide appropriate genetic counseling and a mutational screening in the at-risk relatives. The c.1901A>T (p.Lys634 Met) is a novel variant that could be responsible for a severe form of Wolfram syndrome with early and proliferative diabetic retinopathy.

Association of Vitamin D Receptor Gene Polymorphisms With the Evolution of MODY Diabetes: Study in Tunisian Patients.

Vitamin D (VD) cannot be considered as a true vitamin, but rather as a hormone, which exerts its action via a vitamin D receptor (VDR). Many genes have been shown to be involved in the evolution of diabetes in various populations, such as the vitamin D receptor gene. The aim of our study was to investigate if BsmI, TaqI, ApaI, FokI, and Tru9I, polymorphisms of VDR gene have an impact on MODY diabetes and its clinical aspects in a Tunisian population. A total of 95 patients and 153 controls were genotyped using PCR-RFLP. The comparison of the allelic and genotypic frequencies of the five polymorphisms between MODY subjects and control groups revealed the association of MODY diabetes with TaqI, Tru9I and BsmI polymorphisms and no significant differences were observed in the distributions for the ApaI and FokI polymorphisms. After stratification with biochemical and clinical parameters and TaqI, Tru9I and BsmI polymorphisms, we found an association between the three SNPs and different parameters such as age of diagnosis, therapy, hsCRP and HDL-C levels. Our results revealed that TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes. The possible role of vitamin D in the pathogenesis of MODY is far from being completely understood. Further knowledge on this issue may identify new candidate targets in the treatment and prevention of the disease. Our findings suggest that the TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes.

Association of HLA Alleles with Primary Sjögren Syndrome in the South Tunisian Population.

OBJECTIVE: In order to investigate human leukocyte antigen (HLA) genes predisposing to primary Sjögren syndrome (pSS), we conducted an association study using HLA loci (A, B, and DRB1) and 9 polymorphic microsatellite markers spanning the HLA region in pSS patients as compared to healthy individuals. SUBJECTS AND METHODS: Forty-four patients fitting the European criteria of pSS and 123 healthy controls were analyzed for their HLA class I and class II alleles. HLA class I typing was performed using a standard microlymphocytotoxicity method followed by PCR-SSP. HLA-DRB1 genotyping was performed using PCR-SSP. We studied the polymorphism of 9 microsatellite markers for both groups. Microsatellite genotyping was performed using the PCR fluorescent technique. RESULTS: We observed a positive association between HLA-B15 and pSS in the Tunisian population (p = 0.004, OR 7.57). The comparison of the frequencies of DRB1 alleles in pSS patients and controls confirmed the association of the DRB1*03 allele with pSS (p = 0.02, OR 2.36). On the other hand, the association study of microsatellite markers showed that the a9 allele of D6S265 marker and the a20 of C1.2.C were found to be positively associated with pSS as compared to controls (p =0.0003, OR 10.29, and p =0.001, OR 4.79, respectively). Using the "Haplo.stats" software analysis, we found that the most associated region was located in the HLA class I region and limited by HLA-A and D6S265 loci (p = 0.00056). CONCLUSION: The results of this study support the hypothesis of the existence of a susceptibility gene for pSS located in the HLA class I and III regions.

What is the interest of the electroencephalogram in the syndromic diagnosis?

INTRODUCTION: The identification of the epileptic syndrome is a challenge particularly in childhood epilepsies. In fact, the diagnosis may need several years to be fulfilled. OBSERVATION: Our patient presented at the age of 3 years 6 months atypical absence. His electroencephalogram (EEG) showed generalized spikes and waves andpolyspikes and waves. At age 6, he has developed other types of seizures: slow fall of the head, shoulders jerks,slow fall to the side and loss of consciousness. All these phenomena were organized in a fortuitous and variable association from one period to another over 2 years. Meanwhile, the child developed cognitive impairment. EEG showed fast rhythms in sleep and waking. It was only at the age of 8years, whenthe child developedtonic seizures,that we made the diagnosis of Lennox-Gastaut syndrome. CONCLUSION: In the absence of Specific Markers, syndromic diagnosis in epilepsy remains Electro- clinical.

Implementation of effective transition from pediatric to adult diabetes care: epidemiological and clinical characteristics-a pioneering experience in North Africa.

AIMS: Type 1 diabetes is increasing in children leading more T1D young adults to adult healthcare settings. This change is experienced as a tear and results in a disengagement from specialist services. This study reports on an implementation of an effective and pioneering program of transition in North Africa. METHODS: A total of 65 teenagers with T1D were recruited for a structured program of transition. They attend transitional meetings involving both pediatric and adult team and were, when ready, welcomed in specialized consultations for adolescents with a special « passport ¼. Here we study their characteristics before and after structured transition and the benefit of this program. RESULTS: 9 transition meetings took place (September 2012-December 2017). Mean age was 16.5 years. Mean age at onset of T1D was 7.5 years with average pediatric follow-up of 9 years.72% of young adults felt satisfied. After the transition meeting, 74% of patients wished to join directly adult unit. They were followed there for 28.4 ± 16.2 months. The glycaemic control improved significantly with a decrease in HbA1C of 0.93 ± 1.69% the first year of follow-up and the number of young adults achieving a HbA1C < 7.5% increased by 8%. CONCLUSION: This program was beneficial for 75% of patients who demonstrated an improvement in their metabolic control the year following transition to adult care service. To our knowledge, this study is the first one in North Africa to report on the outcome of a structured transition program from pediatric to adult diabetes care.

Developed diplopia due to a pituitary macroadenoma during pregnancy.

Physiologic pituitary enlargement is common during normal pregnancy. However, symptoms such as diplopia, blurred vision and headache resulting from physiologic pituitary enlargement are very rare during pregnancy. A 43-year-old woman complained of sudden headache and left eye ptosis at 36th weeks of gestation. An magnetic resonance imaging (MRI) demonstrated the pituitary enlargement and a macroadenoma without a compressing of the optic chiasm, but with an extension to the left cavernous sinus. 48 hours after the prescription of the bromocriptine, we had a spectacular evolution with disappearance of the headache and a total regression of the ptosis. We report a case of visual loss due to the physiologic pituitary enlargement or to the macroadenoma during pregnancy, which regressed after the prescription of bromocroptine.

A reappraisal of small- and large-fiber damage in carpal tunnel syndrome: New insights into the value of the EMLA test for improving diagnostic sensitivity.

OBJECTIVES: To reappraise the respective involvement of small- and large-fiber damage in carpal tunnel syndrome (CTS) and to determine the diagnostic sensitivity of autonomic tests compared to conventional nerve conduction study (NCS). METHODS: Thirty-two manual workers complaining of at least unilateral CTS were enrolled. They underwent clinical interview and completed the symptom severity scale of the Boston CTS Questionnaire (sssBCTQ) and the Neuropathic Pain Symptom Inventory (NPSI). In addition, transcarpal NCS was performed to investigate large sensory and motor fibers of the median nerve, while small autonomic fibers were assessed by recording sympathetic skin reflexes (SSR) at the palm and by grading skin wrinkling in response to eutectic mixture of local anesthetic (EMLA) cream application at the pulp of the index finger. For each neurophysiological variable, sensitivity and specificity values for the diagnosis of CTS were calculated and clinical correlations were studied. RESULTS: Among 64 hands examined, 36 were clinically symptomatic, while 22 were clinically asymptomatic and served as controls. Among all the neurophysiological variables studied, only the values of transcarpal sensory nerve conduction velocity and the EMLA test grade were found to be more altered in clinically symptomatic hands, with also a trend towards prolonged distal motor latency. Overall, for the diagnosis of clinically symptomatic CTS, NCS, SSR, and the EMLA test had a sensitivity of 66.7%, 22.2%, and 69.4%, respectively, and a specificity of 72.7%, 90.9%, and 50%, respectively. Combining NCS and the EMLA test led to a sensitivity of 88.9% and a specificity of 45.4%. The sssBCTQ (r=-0.34, P=0.009) and the total NPSI score (r=-0.41, P=0.001) correlated to a more altered EMLA test grade, but not to any NCS or SSR variables. In symptomatic hands, burning sensation was associated with more severe small-fiber lesion, while other pain and sensory symptoms were rather found to be reduced in case of large-fiber damage, evidenced by NCS alteration. CONCLUSIONS: This study confirms the discrepancy between conventional NCS results and clinical presentation of CTS, but still suggests a major involvement of Aß fibers in the positive sensory symptoms of CTS, excepting burning sensation. On the other hand, the EMLA test was found to correlate with clinical data and to be able to improve sensitivity of neurophysiological investigation in diagnosing CTS.

Change in women's eating habits during the menstrual cycle.

OBJECTIVES: During the menstrual cycle, the influence of hormonal variations on dietary habits in women has been suggested by several studies. In this context, our work aimed to assess the spontaneous food intake and the anthropometric parameters of women at different periods of their menstrual cycles. METHODS: This prospective study included 30 healthy women with regular periods (28 to 30 days), aged between 18 and 45. We assessed the spontaneous food intake and the anthropometric measurements (weight and waist circumference) of the participants, during the follicular, peri-ovulatory and luteal phases of their menstrual cycles. RESULTS: Our results showed a slight but significant increase in body weight during the luteal phase (P=0.022) and the follicular phase (P=0.017) compared with the peri-ovulatory phase, without any significant change in waist circumference. The caloric intake increased during the peri-ovulatory (P<0.001) and the luteal phases (P<0.001), compared with the follicular phase, with a significant increase in carbohydrate (P<0.001), lipid (P=0.008) and protein (P=0.008) intake. CONCLUSIONS: Our study showed a significant decrease in women's weight during the peri-ovulatory phase, with a significant increase in caloric intake during the luteal phase of the menstrual cycle. Divergent results have been reported by other authors and the physiopathology of these changes is still poorly understood.

[Continuous glucose monitoring in glimipiride plus metformin treated type 2 diabetic patients during the month of Ramadan]. / Enregistrement continu du glucose pendant Ramadan chez des diabétiques de type 2 sous glimépiride et metformine.

BACKGROUND: Fasting during Ramadan may be a cause of poor glycaemic control in diabetic patients. AIM: To assess glucose excursions during Ramadan by using a continuous glucose monitoring system (CGMS). METHODS: The interstitial glucose level was recorded over 72 hours during Ramadan and three months later, in five type 2 diabetic patients, aged 56 ± 5, treated with glimepiride and metformin. RESULTS: During Ramadan, four patients experienced at least one episode of low glucose level (<0.7 g/l) during the monitoring. The frequency of these episodes was 0.6 episode/d with an average duration of 36 mn / d. These episodes occurred in the morning in half of the cases and in the hour before breaking the fast in 37.5 % of the cases. Four patients experienced at least one episode of high glucose level (>1.8 g/l), with an average duration of 403 mn /d and with a frequency of two episodes /d. More than half episodes (53) occurred after the breaking of the fast. After Ramadan, CGM records showed at least one episode of low glucose in two patients with an average duration of 58 mn /d and a frequency of 1.3 episodes/d. Three patients experienced at least one episode of high glucose level with an average duration of 525 mn /d and a frequency of 1.46 episodes/day. CONCLUSION: The blood glucose profile of our patients during Ramadan is characterized by important glycaemic excursions.