Diabetic foot in patients below 40 years of age

Data on diabetic foot ulcers (DFU) in young patients are scarce. We aimed to examine the risk factors, clinical presentation, wound characteristics, and outcome of DFU among young diabetic patients and to compare them with similar age diabetics without foot ulcer and those of older age diabetics with foot ulcers. A prospective cohort of 745 patients (834 ulcers) below 40 years of age, 7620 patients (9405 ulcers) ages 40 years and above, and 992 patients below 40 years diabetics without foot ulcers in a single multidisciplinary diabetes center were studied. Registered patients with foot ulcers in Jabir Abu Eliz Diabetes Centre (JADC) in Khartoum, Sudan from March 2001 to Dec 2011 were reviewed. Below 40 years of age constituted 8.9 % (n?=?7450) of all patients with DFU. Male-to-female ratio was 1.7:1. IDDM type was prevalent in 60.9 %. Thirty-six per cent of below 40 years had peripheral neuropathy compared to 61.6 % of older group (p?<?0.0002) and 8.7 % of below 40 without DFU (p?<?0.0002). ABI <0.9 was found in 38.7 % (n?=?288) in below 40 years with ulcers compared to 41.4 % in older patients (p?=?0.8989) and 36.3 % (n?=?360) of below 40 without DFU (p?=?0.3125). HbA1c >7 % was significantly more in diabetics below 40 years with foot ulcers compared to those without foot ulcers (83.5 vs. 75.1 %) (p?=?0.0002). In below 40 years of age, 80.1 % of ulcers healed compared to 70.6 % in older age group (p?>?0.0002). Major lower extremity amputation was performed in 4.8 % in below 40 years patients compared to 7.3 % in older group (0.0105). Young diabetics with foot ulcers had significantly longer duration of the disease, more foot deformities, and callus formation and more severe neuropathy than young diabetics without ulcers but had a lesser duration of diabetes than elderly diabetics with foot ulcers. HbA1c in young diabetics with foot ulcers was significantly higher than young diabetics without ulcers, and their foot ulcers healed better and with less major lower extremity amputation than elderly patients.     

Metabolic profile of oxidative stress and trace elements in febrile seizures among children

Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and young children. The present study aims to assess and compare the serum levels of oxidative stress markers and some essential trace minerals in FS with normal or abnormal EEG and evaluate the effect of antioxidant therapy on the clinical outcome. This study has been carried out on 80 children with FS (40 with simple FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and EEG findings were recorded for the included patients. Biochemical assays of serum nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper (Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in the studied groups. The overall results showed an increased values of NO, MDA and Cu with decreased values of SOD, Zn and Se in patients with FS (simple and complex) in comparison with febrile children without seizures (p?<?0.05 for all). Additionally, NO and MDA was increased in complex FS patients with EEG abnormalities in comparison with complex FS with normal EEG findings (p?<?0.05); NO and MDA were also significantly decreased after valproate therapy in complex FS patients (p?<?0.05 for all). In conclusions, oxidative stress, decreased Zn and Se with increased Cu may play a role in FS. Valproate improves the oxidative stress status in complex FS.     

Regulation of vascular endothelial growth factor receptor-1 expression by specificity proteins 1, 3, and 4 in pancreatic cancer cells

Vascular endothelial growth factor receptor-1 (VEGFR1) is expressed in cancer cell lines and tumors and, in pancreatic and colon cancer cells, activation of VEGFR1 is linked to increased tumor migration and invasiveness. Tolfenamic acid, a nonsteroidal anti-inflammatory drug, decreases Sp protein expression in Panc-1 and L3.6pl pancreatic cancer cells, and this was accompanied by decreased VEGFR1 protein and mRNA and decreased luciferase activity on cells transfected with constructs (pVEGFR1) containing VEGFR1 promoter inserts. Comparable results were obtained in pancreatic cancer cells transfected with small inhibitory RNAs for Sp1, Sp3, and Sp4 and all three proteins bound to GC-rich elements in the VEGFR1 promoter. These results show that VEGFR1 is regulated by Sp proteins and that treatment with tolfenamic acid decreases expression of this critical angiogenic factor. Moreover, in vitro studies in Panc-1 cells show that activation of VEGFR1 by VEGFB to increase mitogen-activated protein kinase 1/2 phosphorylation and cell migration on collagen-coated plates is also inhibited by tolfenamic acid. Thus, targeted degradation of Sp proteins is highly effective for inhibiting VEGFR1 and associated angiogenic responses in pancreatic cancer.     

Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells

HER2 overexpression is one of the most recognizable molecular alterations in breast tumors known to be associated with a poor prognosis. In the study described here, we explored the effect of HER2 overexpression on the sensitivity of breast cancer cells to the growth-inhibitory effects of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), a synthetic triterpenoid, both in vitro and in vivo in a xenograft model of breast cancer. Both cell growth and colony formation in the soft agar assay, a hallmark of the transformation phenotype, were preferentially suppressed in HER2-overexpressing cell lines at low concentrations of CDDO, whereas growth-inhibitory effects at high concentrations did not correlate with the expression level of HER2. CDDO dose-dependently inhibited phosphorylation of HER2 in HER2-overexpressing cells and diminished HER2 kinase activity in vitro. CDDO induced the transactivation of the nuclear receptor peroxisome proliferator-activated receptor-gamma in both vector control and HER2-transfected MCF7 cells. Dose-response studies showed that the growth inhibition seen at lower concentrations of CDDO correlated with induction of the tumor suppressor gene caveolin-1, which is known to inhibit breast cancer cell growth. CDDO also reduced cyclin D1 mRNA and protein expression. In vivo studies with liposomally encapsulated CDDO showed complete abrogation of the growth of the highly tumorigenic MCF7/HER2 cells in a xenograft model of breast cancer. These findings provide the first in vitro and in vivo evidence that CDDO effectively inhibits HER2 tyrosine kinase activity and potently suppresses the growth of HER2-overexpressing breast cancer cells and suggest that CDDO has a therapeutic potential in advanced breast cancer.     

Clinical and molecular spectrum of a large Egyptian cohort with ALS2-related disorders of infantile-onset of clinical continuum IAHSP/JPLS

This study presents 46 patients from 23 unrelated Egyptian families with ALS2-related disorders without evidence of lower motor neuron involvement. Age at onset ranged from 10 months to 2.5 years, featuring progressive upper motor neuron signs. Detailed clinical phenotypes demonstrated inter- and intrafamilial variability. We identified 16 homozygous disease-causing ALS2 variants; sorted as splice-site, missense, frameshift, nonsense and in-frame in eight, seven, four, three, and one families, respectively. Seven of these variants were novel, expanding the mutational spectrum of the ALS2 gene. As expected, clinical severity was positively correlated with disease onset (p = 0.004). This work provides clinical and molecular profiles of a large single ethnic cohort of patients with ALS2 mutations, and suggests that infantile ascending hereditary spastic paralysis (IAHSP) and juvenile primary lateral sclerosis (JPLS) are belonged to one entity with no phenotype–genotype correlation.     

Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause‐specific hazard of kidney function decline, and the Fine–Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft‐versus‐host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.     

Taurine prevents high‐fat diet‐induced‐hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element‐binding proteins and activation of AMPK

This study investigated if the protective effect of taurine against high fat diet‐induced hepatic steatosis involves modulating the hepatic activity of 5' AMP‐activated protein kinase (AMPK) and levels/activity of the sterol regulatory element‐binding proteins‐1/2 (SREBP1/2). Rats were divided into four groups (n = 12/group) as (a) STD, fed standard diet (3.85 kcal/g); (b) STD + taurine (500 mg/kg); (c) HFD, fed HFD (4.73 kcal/g); and (d) HFD + taurine. All treatments were conducted for 12 weeks. Independent of food intake or modulating glucose or insulin levels, taurine administration to STD and HFD‐fed rats significantly lowered weekly weight gain and the accumulation of the retroperitoneal, visceral and subcutaneous fats. In both groups, taurine also reduced serum and hepatic levels of triglycerides and cholesterol and reduced hepatic mRNA and protein levels of fatty acid synthase (FAS), acetyl CoA carboxylase‐1 (ACC‐1), HMG‐CoA‐reductase and HMG‐CoA synthetase. In control rats only, taurine reduced hepatic levels of mature forms of sterol regulatory element‐binding proteins (SREBP)‐1/2. In HFD‐fed rats, taurine reduced SREBP‐1/2 precursor and mature forms in the livers of HFD‐fed rats. Besides, taurine significantly increased levels of glutathione (GSH), the activity of superoxide dismutase (SOD), and the activity of AMPK and its downstream β‐oxidation genes including peroxisome proliferator‐activated receptor‐α (PPAR‐α) and carnitine palmitoyltransferase (CPT‐1) in the livers of both the control and HFD‐fed rats. In conclusion, taurine protects against HFD‐induced hepatic steatosis stimulating antioxidant levels, and concomitant stimulating hepatic β‐oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP‐1.     

Acute pericarditis complicated with pericardial effusion as first presentation of COVID‐19 in an adult sudanese patient: A case report

Acute pericarditis is an uncommon presentation of COVID‐19. Here, we described a case of a 50‐year‐old male patient who presented with chest pain without fever or cough and diagnosed with acute pericarditis complicated by pericardial effusion due to COVID‐19 after exclusion of other causes and received supportive treatment and improved over two weeks.