A novel allelic donkey ß-lactoglobulin I protein isoform generated by a non-AUG translation initiation codon is associated with a nonsynonymous SNP.

ß-lactoglobulin I (ß-LG I) is one of the most important whey proteins in donkey milk. However, to our knowledge, there has been no study focusing on the full nucleotide sequences of this gene (BLG I). Current investigation of donkey BLG I gene is very limited with only 2 variants (A and B) characterized so far at the protein level. Recently, a new ß-LG I variant, with a significantly higher mass (+1,915 Da) than known variants has been detected. In this study, we report the whole nucleotide sequence of the BLG I gene from 2 donkeys, whose milk samples are characterized by the ß-LG I SDS-PAGE band with a normal electrophoretic mobility (18,514.25 Da, ß-LG I B1 form) the first, and by the presence of a unique ß-LG I band with a higher electrophoretic mobility (20,428.5 Da, ß-LG I D form) the latter. A high genetic variability was found all over the 2 sequenced BLG I alleles. In particular, 16 polymorphic sites were found in introns, one in the 5' flanking region, 3 SNPs in the 5' untranslated region and one SNP in the coding region (g.1871G > A) located at the 40th nucleotide of exon 2 and responsible for the AA substitutions p.Asp28 > Asn in the mature protein. Two SNPs (g.920-922CAC > TGT and g.1871G/A) were genotyped in 93 donkeys of 2 Italian breeds (60 Ragusana and 33 Amiatina, respectively) and the overall frequencies of g.920-922CAC and g.1871A were 0.3065 and 0.043, respectively. Only the rare allele g.1871A was observed to be associated with the slower migrating ß-LG I. Considering this genetic diversity and those found in the database, it was possible to deduce at least 5 different alleles (BLG I A, B, B1, C, D) responsible for 4 potential ß-LG I translations. Among these alleles, B1 and D are those characterized in the present research, with the D allele of real novel identification. Haplotype data analysis suggests an evolutionary pathway of donkey BLG I gene and a possible phylogenetic map is proposed. Analyses of mRNA secondary structure showed relevant changes in the structures, as consequence of the g.1871G > A polymorphism, that might be responsible for the recognition of an alternative initiation site providing an additional signal peptide. The extension of 19 AA sequence to the mature protein, corresponding to the canonical signal peptide with an additional alanine residue, is sufficient to provide the observed molecular weight of the slower migrating ß-LG I encoded by the BLG I D allele.

Guía práctica de las nuevas alternativas terapéuticas frente a SARS-CoV-2 en pacientes con inmunomoduladores de uso frecuente en dermatología / Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators

En dermatología es frecuente el uso de inmunosupresores e inmunomoduladores, algunos de los cuales pueden predisponer al desarrollo de enfermedad grave por SARS-CoV-2. Las nuevas terapias antivirales frente al SARS-CoV-2 han demostrado reducir la progresión a neumonía por COVID-19 grave en pacientes susceptibles. El pasado 23 de mayo, la Agencia Española de Medicamentos y Productos Sanitarios publicó la última actualización sobre los criterios para la priorización en el acceso precoz a estos fármacos debido a su limitada disponibilidad. En esta guía práctica revisamos los pacientes dermatológicos que en caso de contraer COVID-19 leve-moderada pueden beneficiarse de los nuevos antivirales, así como su indicación (AU)

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology (AU)

[Translated article] Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators / Guía práctica de las nuevas alternativas terapéuticas frente a SARS-CoV-2 en pacientes con inmunomoduladores de uso frecuente en Dermatología

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology (AU)

En dermatología es frecuente el uso de inmunosupresores e inmunomoduladores, algunos de los cuales pueden predisponer al desarrollo de enfermedad grave por SARS-CoV-2. Las nuevas terapias antivirales frente al SARS-CoV-2 han demostrado reducir la progresión a neumonía por COVID-19 grave en pacientes susceptibles. El pasado 23 de mayo, la Agencia Española de Medicamentos y Productos Sanitarios publicó la última actualización sobre los criterios para la priorización en el acceso precoz a estos fármacos debido a su limitada disponibilidad. En esta guía práctica revisamos los pacientes dermatológicos que en caso de contraer COVID-19 leve-moderada pueden beneficiarse de los nuevos antivirales, así como su indicación (AU)

Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators. / Guía práctica de las nuevas alternativas terapéuticas frente a SARS-CoV-2 en pacientes con inmunomoduladores de uso frecuente en dermatología.

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology.