Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome

Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of lens, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described for WMS. A locus for AR WMS has recently been mapped to chromosome 19p13.3-p13.2 while mutation within the fibrillin-1 gene (15q21.1) was found in one AD WMS family. In order to answer the question of whether or not genetic heterogeneity could be related to a clinical heterogeneity, we reviewed 128 WMS patients from the literature (including 57 AR, 50 AD, and 21 sporadic cases), with a particular attention to clinical features. Statistical analyses using Fischer exact test were used to compare the proportions of 12 clinical parameters between AR and AD patients. There was no significant difference between both groups for myopia, glaucoma, cataract, short stature, brachydactyly, thick skin, muscular build, and mental retardation. Significant results were found for microspherophakia (94% in AR, 74% in AD, Fischer 0.007), ectopia lentis (64% in AR, 84% in AD, Fischer 0.016), joint limitations (49% in AR, 77% in AD, Fischer 0.010), and cardiac anomalies (39% in AR, 13% in AD, Fischer 0.004). Nevertheless, we failed to distinguish AR from AD inheritance in individual cases. These results support the clinical homogeneity but the genetic heterogeneity of WMS.     

Giant right coronary artery aneurysm secondary to Kawasaki disease in an infant

Kawasaki disease (KD) is a potentially decapacitating multisystemic vasculitis with unknown etiology that acquired worldwide attention due to associated coronary aneurysms leading to life-threatening complications in very young babies including thrombosis, ischemia, and rupture. High levels of suspicion for early diagnosis and prompt treatment are crucial in preventing serious complications. We report here one of the patients who developed a giant coronary aneurysm but fortunately not a life-threatening complication after 5?years of follow-up. We conclude that later intravenous immunoglobulins (IVIG) treatment could be an important factor—among others—that precipitate into such complications.     

Neuroschistosomiasis mimicking lower back pain: case report of a rare differential diagnosis in a pediatric patient

Background

Spinal myelitis is an infrequent manifestation of spinal cord infection. It is caused by the Schistosoma species, which are endemic in South America, part of the Middle East, and Africa.

Case presentation

We report the case of a 13-year-old male adolescent complaining of progressive lower back pain and weakness of the lower extremities for 3 days. Initial magnetic resonance imaging revealed typical transverse myelitis. Subsequently, parasite serology showed a markedly elevated level of Schistosoma antibody titers, and cerebrospinal fluid analysis yielded normal results. Because of our presumptive diagnosis of neuroschistosomiasis, the patient was prescribed an empirical regimen of an anti-parasitic agent, after which his neurological deficit promptly subsided. The patient was followed for 1 year and showed a complete long-term resolution of symptoms.

Conclusions

This case highlights the increasing prevalence of neuroschistosomiasis in recent years, particularly in patients with a history of travel to endemic regions. Moreover, the study reports the clinicoradiological features of this enigmatic disorder. This rare occurrence potentiates further studies to address unanswered questions about neuroschistosomiasis.

     

Invasive breast carcinomas with ATM gene variants of uncertain significance share distinct histopathologic features

The increasing availability of next‐generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy.     

Thoracoscopic division of vascular rings in infants and children

Objective

Traditionally vascular rings in infants and children are treated through an open thoracotomy. Recently, thoracoscopic surgery has been used for these complex procedures. This study reports our early experience with thoracoscopic division of vascular rings and evaluates the efficacy and safety of this approach.

Material and Methods

Patients who underwent thoracoscopic division of vascular rings at King Khalid University Hospital, Riyadh, Saudi Arabia, from December 2004 to January 2006 are included. Their data were carefully analyzed looking at demographics, clinical presentation, diagnostic modality, type of the anomaly, operative details, complications, and outcome.

Results

A total of 9 patients underwent thoracoscopic division of vascular rings. Age at surgery ranged between 2 and 108 months (mean, 24 months). Weight varied between 5.3 and 32 kg (mean, 10.3 kg). All patients were symptomatic. Computed tomographic scan was diagnostic and accurately defined the type of anomaly in all the patients. Four patients had a right aortic arch with an aberrant left subclavian artery and left ductus/ligamentum arteriosum, 2 had double aortic arches, and 3 had a right aberrant subclavian artery. One patient developed right-sided pneumothorax on the contralateral site, and another one developed apnea 12 hours after surgery, requiring mechanical ventilation. There was no mortality. Operative time ranged between 50 and 145 minutes, the mean being 107 minutes. The average hospital stay was 4 days. Five patients had their preoperative symptoms completely resolved, and the rest are showing steady improvement. The average follow-up period is 6 months.

Conclusion

Our early experience indicates that thoracoscopic division of vascular rings is safe and effective. Because it takes away the need for thoracotomy, it is likely that it can result in less postoperative pain and rapid convalescence. It also prevents the ill effects of thoracotomy and gives good cosmetic results.     

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in pediatric brain tumors

Brain tumors are the most common solid tumor in childhood. Surgery and/or fractionated radiotherapy are conventional treatment modalities. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are advanced radiation therapy techniques that have been frequently used in adults with brain tumors but they are less frequently used in pediatric patients. SRS and FSRT can potentially add to the armamentarium against brain tumors in children. This article will review the role of SRS and FSRT in the management of pediatric brain tumors.     

Recent evolution of a novel begomovirus causing tomato leaf curl disease in the Al-Batinah region of Oman

For last two decades, begomoviruses (family Geminiviridae) have been a major constraint for tomato production in Oman, particularly in the Al-Batinah region, the major agricultural area of Oman. Farms in the Al-Batinah region were surveyed during January-March and November-December in 2012 and January-February in 2013. Leaf samples of tomato plants showing typical leaf curl disease symptoms were collected and analyzed for begomoviruses. Out of fifteen begomovirus clones sequenced, seven were shown to be tomato yellow leaf curl virus strain Oman (TYLCV-OM); three, chili leaf curl virus strain Oman (ChLCV-OM); and one, tomato leaf curl Oman virus (ToLCOMV) – viruses that have previously been shown to occur in Oman. Four sequences were shown to have relatively low percent identity values to known begomoviruses, with the highest (86 %) to isolates of pepper leaf curl Lahore virus, indicating that these should be included in a new species, for which the name “Tomato leaf curl Al Batinah virus” (ToLCABV) is proposed. Although the betasatellite tomato leaf curl betasatellite (ToLCB; 7 full-length sequences isolated) was identified with some isolates of ChLCV-OM, TYLCV-OM and ToLCOMV, it was not identified in association with any of the ToLCABV isolates. Analysis of the sequences of the TYLCV-OM and ToLCOMV isolates characterized here did not show them to differ significantly from previously characterized isolates of these viruses. The three isolates of ChLCV-OM characterized were shown to have a recombination pattern distinct from earlier characterized isolates. ToLCABV was shown to have resulted from recombination between ChLCV-OM and ToLCOMV. A clone of ToLCABV was infectious by Agrobacterium-mediated inoculation to Nicotiana benthamiana and tomato, inducing symptoms typical of those seen in tomato in the field. Additionally, ToLCABV was shown to be able to interact in planta with ToLCB, resulting in a change in symptom phenotype, although the betasatellite did not appear to affect viral DNA levels.     

Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction

Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO.) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO. was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography -based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H2O2 production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or glibenclamide. Depletion of p22(phox) subunit of NADPH oxidase with small interfering RNA also inhibited Ang II-mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione, increased state 4 and decreased state 3 respirations, and diminished mitochondrial respiratory control ratio. These responses were attenuated by apocynin, 5-hydroxydecanoate, and glibenclamide. In addition, 5-hydroxydecanoate prevented the Ang II-induced decrease in endothelial NO. and mitochondrial membrane potential. Therefore, Ang II induces mitochondrial dysfunction via a protein kinase C-dependent pathway by activating the endothelial cell NADPH oxidase and formation of peroxynitrite. Furthermore, mitochondrial dysfunction in response to Ang II modulates endothelial NO. and generation, which in turn has ramifications for development of endothelial dysfunction.     

Polyphenolic Fractions from Three Millet Types (Fonio,Finger millet,and Pearl millet): their Characterization and Biological Importance

BackgroundAs antioxidant-rich plant foods, cereals can impede lipid and starch breakdown in the human body, are germane to diabetes management.ObjectiveWe aim to identify newer sources of phytochemicals and health-promoting constituents desirable antidiabetic and antioxidant properties.MethodsThree millet types i.e. fonio (Digitaria exilis), finger millet (Eleusine coracana), and pearl millet (Pennisetum glaucum) available locally were investigated for antioxidant ability employing these assays i.e. DPPH, ABTS, H₂O₂, antidiabetic ability employing these assays i.e. α-amylase, α-glucosidase and inhibitory property on glycosylation formation. Preliminary characterization tools were employed i.e. UV-Visible spectroscopy (UV–visible) and Fourier-Transform Infrared Spectroscopy (FTIR) for the polyphenolic confirmation.ResultsThe absorbance intensity range 325–425 nm confirmed that polyphenolics are present in the three millet types; most of the biological results showed the activities are dose-dependent. Fonio millet extract revealed the highest activity against hemoglobin glycosylation (29.469 ± 0.399%) which compared favorably with the standard (acarbose) (29.354 ± 1.607%). Fonio millet extract also showed the best antioxidant activity (significantly higher% inhibition value = 47.909 ± 3.472) and the pearl millet revealed the least antioxidant activity (significantly lower% inhibition value = 44.910 ± 3.597) both at a concentration of 500 mg·ml^?1, though all the millet extracts showed activity towards this assay better than the standard (19.883 ± 2.485%). Fonio millet extract displayed a significantly higher percentage inhibition of α-amylase and glucosidase (43.729 ± 0.410% and 55.835 ± 2.198%) than finger millet (39.002 ± 1.604%; 43.971 ± 5.849%) and pearl millet (33.223 ± 2.708%; 30.845 ± 2.841%), respectively.ConclusionThe polyphenolic extracts from these millet types have therapeutic potentials, which may play significant roles in type 2 diabetes prevention and management, and hence these millets, especially fonio and finger millet, have the potential to be utilized as functional foods.