Correction: Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.

Zoe McDonald, BSc, was omitted from the list of article coauthors. Her name should have been included as the seventh author, following Clare Elizabeth Hunt. Her affiliation is Victorian Clinical Genetics Services, Parkville, Victoria, Australia. The authors regret the error.

Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.

PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.ResultsScreening of 12,000 individuals revealed 610 carriers (5.08%; 1 in 20): 342 CF, 35 FXS, 241 SMA (8 carriers of 2 conditions), approximately 88% of whom had no family history. At least 94% of CF and SMA carriers' partners were tested. Fifty couples (0.42%; 1 in 240) were at increased risk of having a child with one of the conditions (14 CF, 35 FXS, and 1 SMA) with 32 pregnant at the time of testing. Of these, 26 opted for prenatal diagnosis revealing 7 pregnancies affected (4 CF, 2 FXS, 1 SMA).ConclusionThe combined affected pregnancy rate is comparable to the population risk for Down syndrome, emphasizing the need to routinely offer carrier screening. The availability of appropriate genetic counseling support and a collaborative approach between laboratory teams, genetics services, health professionals offering screening, and support organizations is essential.

Lobular panniculitis of the thigh as the only cutaneous manifestation of reactivation of Chagas disease in a renal transplant patient: a case report.

Reactivation of chronic Trypanosoma cruzi infection in solid organ transplant recipients (SOTRs) has been reported. The patient presented with a 2-week history of two painful erythematous, infiltrated plaques with central ulceration and necrotic crust on the left thigh. She had a history of chronic indeterminate Chagas disease (CD) and had received a kidney transplant before 2 months. Skin biopsies revealed lobular panniculitis with intracellular amastigote forms of T. cruzi. The patient was diagnosed with CD reactivation. Treatment with benznidazole significantly improved her condition. CD reactivation should be suspected in SOTRs living in endemic areas with clinical polymorphism of skin lesions.

Osteonecrosis in individuals with systemic lupus erythematosus: A predictive model.

OBJECTIVE: This work attempts to provide a model to predict the development of osteonecrosis (ON) in individuals with systemic lupus erythematosus (SLE) using pharmacological, demographic, and psychoactive factors. METHOD: A review of the literature was conducted to construct a survey administered across Chile to individuals with SLE during a period of three weeks. This work used a sample size of 46 de-identified data records. Two Bayesian logistic regression models were created, with non-informative prior and informative prior distributions, and a random forest model was done for comparison. All models were cross-validated. RESULTS: The significant variables used were mean corticosteroids per day (mg) and tobacco use. The random forest model provided good accuracy and sensitivity, but low specificity. Bayesian logistic regression with prior information increased the specificity. CONCLUSIONS: This work determined that the use of corticosteroids and tobacco are significant variables to predict ON. Using prior information provides good accuracy, specificity, and sensitivity to the prediction. Further studies need to be conducted to validate the model using a testing set.

CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion.

CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Recurrent and disseminated pityriasis versicolor: A novel clinical form consequent to Malassezia-host interaction?

Pityriasis versicolor is a superficial fungal infection caused by Malassezia spp. The aim of this study is to propose the definition of a new clinical entity: the recurrent and disseminated pityriasis versicolor (RDPV). All patients with RDPV were enrolled over an eight-month period. Clinical and epidemiological data were obtained, Malassezia (M.) species were isolated in cultures and identified by phenotypic and molecular characterization, skin biopsies were taken from active lesions, serum levels of immunoglobulin E were obtained and therapeutic schemes were evaluated. A total of 16 patients were included (11 male, 5 female). The most frequently isolated species were M. japonica (n = 3) and M. furfur (n = 3). This is the first study that isolates M. japonica in patients with pityriasis versicolor; interestingly, those were recalcitrant patients. Seven patients (43.8%) had no cure with any of the proposed treatments; among those, 5 (71.4%) had increased serum IgE levels. The most effective treatment was itraconazole 200 mg daily for 28 days. The RDPV has very different features from the classic form, including a poor response to treatment, and the isolation of different Malassezia species; therefore, we propose a hypothesis for the definition of a new clinical condition (RDPV), which could be a result of the interaction Malassezia-host.

Lobular panniculitis of the thigh as the only cutaneous manifestation of reactivation of Chagas disease in a renal transplant patient: a case report

Abstract Reactivation of chronic Trypanosoma cruzi infection in solid organ transplant recipients (SOTRs) has been reported. The patient presented with a 2-week history of two painful erythematous, infiltrated plaques with central ulceration and necrotic crust on the left thigh. She had a history of chronic indeterminate Chagas disease (CD) and had received a kidney transplant before 2 months. Skin biopsies revealed lobular panniculitis with intracellular amastigote forms of T. cruzi. The patient was diagnosed with CD reactivation. Treatment with benznidazole significantly improved her condition. CD reactivation should be suspected in SOTRs living in endemic areas with clinical polymorphism of skin lesions.

A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes.

BACKGROUND: The antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer. METHODS: Hydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARbeta, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the "normally methylated" sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria. RESULTS: Hydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150 mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation. CONCLUSION: Hydralazine at doses between 50 and 150 mg/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation.

Ejercicio en ratas con osteoartritis: aspectos morfológicos y una revisión de la literatura / Exercise in rats osteoarthritis: morphological aspects and literature review

La osteoartritis (OA) es una enfermedad crónica, degenerativa, muy invalidante, que destruye en forma gradual y progresiva el cartílago articular en diversas regiones: rodillas, caderas, hombros, manos, tobillos y columna vertebral. En este sentido, el ejercicio ha sido descrito como la intervención no farmacológica más recomendada para pacientes con OA. La práctica regular de ejercicio es considerada un componente integral del estilo de vida saludable; sin embargo, su efecto en el cartílago se mantiene como objeto de debate y especulaciones, así como la relación del ejercicio con el desarrollo de OA. Algunos estudios de modelos animales sugieren que el ejercicio puede ser beneficioso para la salud del cartílago, mientras otros demuestran su efecto nocivo. Una explicación general a estos resultados inconsistentes es que el correr a intensidad moderada tiene efectos beneficiosos, mientras que correr "vigorosamente" o de manera "extenuante" lleva a un efecto nocivo. El objetivo de este trabajo consistió en realizar una revisión de la literatura acerca de los efectos del ejercicio sobre el cartílago artícular, especialmente enfocado a modelos animales experimentales con ratas.

Osteoarthritis (OA) is a chronic, degenerative, and very disabling disease that gradually and progressively destroys articular cartilage in various regions: knees, hips, shoulders, hands, ankles and spine. In this sense, exercise has been described as the most recommended non-pharmacological intervention for patients with OA. Regular exercise is considered an integral component of the healthy lifestyle. However, its effect on cartilage remains the subject of debate and speculation, as well as the relationship between exercise and the development of OA. Some animal model studies suggest that exercise may be beneficial for cartilage health, while others demonstrate its harmful effect. A general explanation for these inconsistent results is that running at moderate intensity has beneficial effects, while running "vigorously" or "strenuously" leads to a harmful effect. The aim of this work was to make a literature review about the effects of exercise on cartilage, especially focused on experimental animal models with rats.

CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.