Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

A case report of combination treatment with potassium-titanyl phosphate laser and brimonidine topical gel in erythematotelangiectatic rosacea

Laser therapies have been shown to provide symptom improvement in patients with erythema and telangiectasia of rosacea; however, they are associated with side effects such as erythema. Combinatorial treatment with pharmacological agents and laser have demonstrated better efficacy, fewer side effects and continued long-term remission compared with monotherapies. A case of moderate facial erythema that responded well to combination treatment with brimonidine 3 mg/g gel and a treatment course of potassium-titanyl phosphate (KTP) laser therapy is presented, showing a reduction from baseline, maintained after final laser session, by applying brimonidine 3 mg/g gel daily. Using brimonidine 3 mg/g gel to target post-laser treatment erythema is highly effective in minimising refractory erythema. Continued use of brimonidine 3 mg/g gel provides a sustained reduction of erythema, increasing the visibility of other signs and symptoms of rosacea that may be present. This can facilitate the treatment of these additional signs and symptoms.     

Prevalence of hair shedding among women

Hair shedding in female patients is a frequent complaint in dermatological, endocrinological, and gynecological consults. Previously, the Sinclair Hair Shedding Scale was developed to assess normal versus excessive hair shedding in female pattern hair loss (FPHL) subjects. However, the prevalence of hair shedding in females not suffering from FPHL is unknown. To gain better understanding of hair shedding in the general population, we recruited 300 subjects visiting a public hospital for conditions other than alopecia. Of the 300 subjects recruited, 263 did not suffer from FPHL. Among those subjects, approximately 40% reported experiencing excessive hair shedding (as defined by the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our subject population, approximately 60% of subjects with FPHL reported excessive hair shedding on hair washing days. To best of our knowledge, this is the first study to quantify the prevalence of hair shedding in women. While, no treatment currently exists for this condition, we hope that this study would encourage physicians and researchers to address this frequent concern.     

Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women

A programme for the prevention of congenital toxoplasmosis in Slovenia involving the screening of pregnant women for Toxoplasma infection is presented. Of 21,270 pregnant women screened for toxoplasmosis between, 1996 and the end of 1999, 13,987 (66%) were seronegative, 7,151 (34%) seropositive and 132 had primary infection; approximately 9/1,000 women were at risk of acquiring the primary infection. One hundred live-born infants of primary infected women were available for follow-up. Nine infected but asymptomatic children were born to mothers who were screened and treated in time and two congenitally infected babies were born to mothers in whom infection was detected too late in pregnancy and who therefore received no adequate treatment. It is suggested that the results obtained in this study outweigh the cost of screening for toxoplasmosis in pregnancy. Pregnant women should always be tested at the beginning of pregnancy and, in cases of seronegativity, should be re-tested in the second and third trimesters of the pregnancy. Toxoplasma primary infected pregnant women and neonates should be treated as soon as possible. However, long-term follow-up of children born to primary infected women would be necessary for an accurate evaluation of the effectiveness of the screening because of the possibility of late onset of symptoms.     

Distribution of emm types among group A streptococcal isolates from Serbia

This is the first study concerning the molecular epidemiology of group A streptococcus in Serbia and includes 145 isolates from patients with various infections during the period 2001–2007. The emm types, superantigen profile and susceptibility pattern were determined. Among 31 emm types identified, the most prevalent were emm6, emm12, emm1, and emm58. All isolates showed uniform antimicrobial susceptibility to all tested antibiotics, with the exception of tetracycline and erythromycin (41% and 0.7% resistant strains, respectively). Significant heterogeneity of emm types was found, with a high frequency of emm6 and emm58, as well as a considerable prevalence of tetracycline resistance, and a low level of macrolide resistance.     

Open volume in bioadhesive detected by positron annihilation lifetime spectroscopy

Barnacles attach to a wide variety of surfaces underwater and show substrate-specific adhesion mechanisms. Investigating and understanding these mechanisms is a key for developing new technical adhesives. We expected open volume (porosity) at the sub-nanometre scale to occur in barnacle adhesive. With positron annihilation lifetime spectroscopy (PALS) it is possible to detect porosity at the nanometre scale by determining the lifetime of positrons. This method has not been applied to bioadhesives so far. We showed that PALS is a suitable technique for the investigation of the barnacle base and its adhesive with respect to open volume. The results were interpreted using a standard model adapted from polymers. We thereby estimated pore sizes of 0.5 nm.