Where do we stand with IPF treatment?

Despite receiving 'weak no' recommendations in the updated guidelines on treating patients with Idiopathic Pulmonary Fibrosis (IPF), two key treatment options are pirfenidone and N-acetylcysteine (NAC), and both are used in clinical practice. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis. Tolerability data are also provided by clinical trials and a long-term extension phase of these studies. Pirfenidone is approved in Europe for the treatment of patients with mild-to-moderate IPF. NAC-based therapy has no such approval, but is commonly used to treat patients. A Phase III trial suggested some benefit of the NAC, prednisone and azathioprine regimen for IPF patients, but the study had many limitations. A further study to investigate this regimen, compared with a placebo alone arm, was recently stopped due to increased mortality in the triple-therapy arm. Discussion of these data and recent findings highlight the importance of a further update to the existing guidelines, so that IPF specialists can provide the most up-to-date advice and treatment to patients in clinical practice.

Single-nucleotide polymorphisms in 3'-untranslated region inducible costimulator gene and the important roles of miRNA in alopecia areata.

Background: Alopecia areata (AA) spares the stem cell compartment and attacks only the base of the hair follicle, which is surrounded by infiltrating lymphocytes. AA is associated with polymorphisms in immune-related genes and with decreased function of CD4+CD25+ T regulatory (Treg) cells. Treg function is modulated by the costimulatory molecules, like inducible costimulator (ICOS) that are crucial in orienting T cell differentiation and function so that they strongly impact on the immunologic decision between tolerance or autoimmunity development. Objective: The aim of our study was to investigate the possible association of AA with single-nucleotide polymorphisms (SNP) present in the ICOS 3'-untranslated region (3'UTR) region and to elucidate how SNPs modulate ICOS gene expression by affecting miRNA binding sites. Methods: This is a case-control study performed in 184 patients with AA and 200 controls. ICOS gene and miRNA expression were analyzed by real-time polymerase chain reaction. Results: The genotype carrying the rs4404254(C) [p = 0.012, OR (95% CI): 0.5 (0.3-0.8)] and rs4675379(C) [p = 0.015, OR (95% CI): 0.3 (0.1-0.8)] 3' UTR alleles was more frequently observed in AA patients than in controls and correlated with a reduced ICOS expression. miR-1276 significantly suppressed ICOS expression by binding to the 3'UTR of ICOS mRNA. Also, we observed that, miR-101 and miR-27b are upregulated, while miR-103 and miR-2355-3p are downregulated in peripheral blood mononuclear cells of AA patients compared to controls. Conclusion: Our data show that rs4404254 and rs4675379 SNPs of ICOS gene are associated with AA and also reveal that the presence of rs4404254 polymorphism correlates with ICOS post-transcriptional repression by microRNA binding.

Quantitative trait loci mapping for leaf length and leaf width in rice cv. IR64 derived lines.

The present study was conducted to identify quantitative trait loci (QTLs) for leaf size traits in IR64 introgression lines (INLs). For this purpose, selected F(2) populations derived from crosses between recurrent parent IR64 and its derived INLs, unique for leaf length and leaf width, were used to confirm QTLs. A total of eight QTLs, mapped on three chromosomes, were identified for the four leaf size traits in six F(2) populations. A QTL for leaf length, qLLnpt-1, in HKL69 was identified around simple sequence repeat (SSR) marker RM3709 on chromosome 1. Two QTLs for flag leaf length, qFLLnpt-2 and qFLLnpt-4, in HFG39 were indentified on chromosomes 2 and 4, respectively. For flag leaf width, a QTL, qFLWnpt-4, in HFG39 was identified around RM17483 on chromosome 4. While another QTL for flag leaf width, qFLWnpt-1, in HFG27 was identified around RM3252 on chromosome 1. A QTL for leaf width, qLWnpt-2, in HKL75 was identified around RM7451 on chromosome 2. For leaf width, two QTLs, qLWnpt-4a, qLWnpt-4b, in HKL48 and HKL99 were identified around RM7208 and RM6909, respectively on chromosome 4. Results from this study suggest the possibilities to use marker-assisted selection and pyramiding these QTLs to improve rice water productivity.

Clinical applications of oro-pharyngo-oesophageal scintigraphy in the study of dysphagia.

The diagnostic approach to patients with dysphagia is well established and relies mainly on videofluoroscopy and endoscopy. Oro-pharyngo-oesophageal scintigraphy permits both a functional and a semi-quantitative study of the various stages of swallowing. Moreover, by means of this investigation, it is possible to estimate the amount of inhaled bolus. Oro-pharyngo-oesophageal scintigraphy with 99mTc-nanocolloid has been found to be easy to use, economical, well tolerated and, supplying precise indications regarding the extent of the swallowing disorder, then permits a better clinical definition of the patient. The limitations of swallowing scintigraphy are: poor definition in visualizing anatomic structures and low specificity when used as the only diagnostic test. Scintigraphy plays an important role in the diagnosis and follow-up of dysphagia, and its use, together with other diagnostic techniques, increases diagnostic accuracy. In this study, the role of oro-pharyngo-oesophageal scintigraphy has been analysed in patients with post-surgical, neurological and oesophageal dysphagia.

Expression of p53 and 17p allelic loss in colorectal carcinoma.

Mutations in the p53 gene are the most common genetic changes in cancer thus far. Many p53 mutations result in a protein product having a prolonged half-life compared to wild-type p53. The mutant protein is frequently detectable immunohistochemically, whereas the wild-type p53 present in normal cells is not. We examined 90 colorectal carcinomas for increased expression of p53 using 3 p53 specific monoclonal antibodies, PAb1801, PAb421, and PAb240. Overall, 70% of the colorectal carcinomas stained for p53. Each tumor's DNA was also assessed for loss of heterozygosity on chromosome 17p, the location of the p53 gene. Of those tumors that reacted with the anti-p53 antibodies, 76% showed loss on chromosome 17p. Tumors with loss of heterozygosity on 17p generally stained with all 3 antibodies, whereas those without loss tended to stain with just one antibody, typically PAb240. Fifteen tumors were examined for the presence of specific p53 mutations. A total of 10 mutations were found, 6 were missense and 2 were deletions, and all but one of the tumors with missense mutations stained for p53.

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia areata.

Alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles, is associated with polymorphisms in immune-related genes and with decreased number of CD4+ CD25+ T regulatory cells (Treg). Treg function is modulated by the forkhead box protein 3 (FOXP3) transcription factor and by inducible costimulator (ICOS), through interaction with the relative ligand, ICOSLG, whose genes are polymorphic. The aim of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) of the rs2294020 FOXP3 and/or rs378299 ICOSLG genes may be associated with AA. A case-control study was performed in 120 AA patients and 84 controls. SNPs were analyzed by gene sequencing. FOXP3 and ICOSLG gene expressions were analyzed by real-time PCR. Increased frequencies of the genotype carrying the FOXP3 rs2294020-3675(A) [P = 0.002, OR (95 % CI): 2.55 (1.2-2.7)] or the ICOSLG rs378299-509(C) [P = 0.01, OR (95 % CI): 2.21 (1.1-2.6)] allelic variants were observed in AA patients than in controls. The genotype carrying the combination of the FOXP3 rs2294020-3675(A) and ICOSLG rs378299-509(C) allelic variants with the HLA DQB1*03 allele was more frequently present in AA patients than in controls (P = 0.04). The presence of the FOXP3 rs2294020-3675(A) or the ICOSLG rs378299-509(C) allelic variant was associated with reduced relative gene expression in AA patients. These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with AA and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients.

[Samuel Hahnemann: a mystical empiricist. A study of the origin and development of the homeopathic medical system]. / Samuel Hahnemann: un empirista mistico. Origine e analisi del sistema medico omeopatico.

Homeopathy is the product of the time of its birth and systematization and its founder's cultural background. From the beginning, homeopathy looked in two directions at the same time. On the one hand, it looked towards scientific enquiry and empirical proof and, on the other, towards religion, metaphysics and mysticism. The origin of this lies in the double orientation of Hahnemann's work: while affirming a rational system of therapeutics based on observation, he also developed a metaphysical theory of illness as well as of the action of medicines.