Tunable locking of calcite narrow frequency filters through modulation switching.

Generating pairs of Raman beams for gravimetry with fiber phase modulators is quite convenient but generates additional frequencies that must be filtered. The frequency filtering could be achieved by using a long (dispersive) birefringent calcite crystal followed by a polarizer that blocks the transmission of certain laser frequencies, as has been shown before. Here, we present a method to tune such a filter to the desired frequency position. The correction signal for the feedback is obtained by comparing (subtracting) the transmission through the filter when sending light that has been phase modulated or not, taking advantage of the fiber modulator that is already installed in the system. The method allows for continuously alternating between using the modulator for monitoring the filter position and other uses, an important characteristic for the operation of a complete gravimetric sequence.

Compact laser modulation system for a transportable atomic gravimeter.

Nowadays, atom-based quantum sensors are leaving the laboratory towards field applications requiring compact and robust laser systems. Here we describe the realization of a compact laser system for atomic gravimetry. Starting with a single diode laser operating at 780 nm and adding only one fiber electro-optical modulator, one acousto-optical modulator and one laser amplifier we produce laser beams at all the frequencies required for a Rb-87 atomic gravimeter. Furthermore, we demonstrate that an atomic fountain configuration can also be implemented with our laser system. The modulated system reported here represents a substantial advance in the simplification of the laser source for transportable atom-based quantum sensors that can be adapted to other sensors such as atomic clocks, accelerometers, gyroscopes or magnetometers with minor modifications.

Vasculopatía coroidea oclusiva tras quimioterapia intraarterial: hallazgos en la RMN / Choroidal occlusive vasculopathy after intraarterial chemotherapy: MRI findings

Objetivo: Evaluar los hallazgos en las imágenes de resonancia magnética nuclear (RMN) en pacientes con vasculopatía coroidea oclusiva (VCO) tras quimioterapia intraarterial (QIA) por retinoblastoma. Métodos: Se realizó un estudio retrospectivo de 37 ojos de 34 pacientes que recibieron QIA entre 2016 y 2021 como tratamiento de primera o segunda línea del retinoblastoma intraocular. De estos pacientes, 22 recibieron quimioterapia sistémica y el resto QIA como primera línea, con melfalán (3-4mg), carboplatino (40mg) y topotecan (20mg). Los pacientes fueron examinados cada mes para observar la regresión tumoral y posibles complicaciones de los tratamientos. A los pacientes que presentaron VCO se les realizaron estudios con RMN para evaluar el grosor coroideo y la longitud del globo ocular. Resultados: Se observó VCO en cinco de los 37 ojos (13,51%), todos ellos con una coroidopatía sectorial completa con afectación foveal (grado 2). En cuatro de los cinco pacientes el grosor coroideo se vio disminuido, mientras que en tres casos el tamaño del globo afectado era claramente inferior. El control tumoral fue posible en todos los casos. Conclusiones:En esta muestra, la VCO se asocia con adelgazamiento coroideo y diminución del tamaño ocular en la RMN. Puede ser necesaria una nueva clasificación para correlacionar mejor la severidad de la coroidopatía que afecta a la fóvea. Los resultados iniciales son favorables respecto al uso de la QIA; aunque es necesaria la realización de estudios a largo plazo y una documentación exhaustiva para valorar tanto el papel de la QIA, como los efectos derivados de ella. (AU)

Purpose: To evaluate magnetic resonance imaging (MRI) findings in patients suffering choroidal occlusive vasculopathy (COV) after intra-arterial chemotherapy (IAC) for retinoblastoma. Methods: A retrospective study of 37 eyes of 34 patients receiving IAQ between 2016 to 2021 as primary or secondary treatment for retinoblastoma was conducted. Twenty-two patients received systemic chemotherapy with carboplatin, vincristine and etoposide. The rest received IAC as primary treatment. The drugs administered were melphalan (3-4mg), carboplatin (40mg) plus topotecan (20mg). The patients were examined under general anaesthesia every month to observe tumor regression and possible complications of the treatment. For the patients with COV an MRI was obtained to analyse the choroidal thickness and axial ocular length. Results: A COV was observed in 5 of the 37 eyes receiving IAC (13,51%), all of them with a complete sectorial choroidopathy not sparing the fovea (grade 2). In 4 of the 5 patients the choroidal thickness was decreased and in three cases the size of the eye which presented COV was clearly smaller than the contralateral eye. Tumor control was archived in all 5 patients. Conclusion: In our cases COV was associated with reduction of thinning of choroid and eye length in the MRI. A new classification maybe needed to correlate better with the severity of the complication affecting the fovea. Although early results generally are favorable to the use of IAC, longer follow up and scrupulous documentation of side effects will be necessary to know the true role of IAC for retinoblastoma. (AU)

Choroidal occlusive vasculopathy after intraarterial chemotherapy: MRI findings.

PURPOSE: To evaluate magnetic resonance imaging (MRI) findings in patients suffering choroidal occlusive vasculopathy (COV) after intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS: A retrospective study of 37 eyes of 34 patients receiving IAQ between 2016 to 2021 as primary or secondary treatment for retinoblastoma was conducted. Twenty-two patients received systemic chemotherapy with carboplatin, vincristine and etoposide. The rest received IAC as primary treatment. The drugs administered were melphalan (3-4mg), carboplatin (40mg) plus topotecan (20mg). The patients were examined under general anaesthesia every month to observe tumor regression and possible complications of the treatment. For the patients with COV an MRI was obtained to analyse the choroidal thickness and axial ocular length. RESULTS: A COV was observed in 5 of the 37 eyes receiving IAC (13,51%), all of them with a complete sectorial choroidopathy not sparing the fovea (grade 2). In 4 of the 5 patients the choroidal thickness was decreased and in three cases the size of the eye which presented COV was clearly smaller than the contralateral eye. Tumor control was archived in all 5 patients. CONCLUSION: In our cases COV was associated with reduction of thinning of choroid and eye length in the MRI. A new classification maybe needed to correlate better with the severity of the complication affecting the fovea. Although early results generally are favorable to the use of IAC, longer follow up and scrupulous documentation of side effects will be necessary to know the true role of IAC for retinoblastoma.

Clinical and neurophysiological response to ephedrine in a patient affected with slow-channel congenital myasthenic syndrome. / Respuesta clínica y neurofisiológica a la efedrina en un paciente con síndrome miasténico congénito de canal lento.

INTRODUCTION: Slow-channel congenital myasthenic syndrome is an autosomal dominant inherited progressive neuromuscular disorder caused by abnormal gating of mutant acetylcholine receptors in the neuromuscular junction. Its pathological hallmark is selective degeneration of the endplate and postsynaptic membrane due to calcium overload. Pyridostigmine should be avoided in this syndrome, being quinidine or fluoxetine the current recommended therapies. CASE REPORT: An 11-year-old girl with a limb-girdle phenotype of slow-channel congenital myasthenic syndrome presenting with a slowly progressive fatigable weakness at the age of 8 years. After a clinical worsening with pyridostigmine, empirically started before the exome sequencing results were available, a dramatic and sustained response to ephedrine monotherapy was observed. Whole exome sequencing revealed a de novo heterozygous mutation in CHRNB1 gene: c.865G>A; p.Val289Met (NM_000747.2). An abnormal decrement in amplitude (23.9%) from the first to fifth intravollley waveform was revealed after repetitive peroneal nerve stimulation at low frequencies. In addition, a second smaller compound muscle action potential after the peak of the main M-wave in median, ulnar and peroneal motor nerves was observed. CONCLUSION: Favorable responses to adrenergic agonists added to fluoxetine had been reported. However, to the best of our knowledge this is the first report on effective monotherapy with ephedrine in a slow-channel congenital myasthenic syndrome patient. Adrenergic agonists may be considered as a therapeutic option in patients with this syndrome.

TITLE: Respuesta clínica y neurofisiológica a la efedrina en un paciente con síndrome miasténico congénito de canal lento.Introducción. El síndrome miasténico congénito de canal lento, o síndrome de canales lentos, es un trastorno neuromuscular progresivo hereditario, autosómico dominante, causado por una activación anormal de los receptores de la acetilcolina en la unión neuromuscular. La alteración histopatológica característica es la degeneración selectiva de la placa terminal y la membrana postsináptica debido a la sobrecarga de calcio. La piridostigmina debe evitarse en este síndrome, y la quinidina o la fluoxetina son las terapias recomendadas actualmente. Caso clínico. Niña de 11 años con un fenotipo de cinturas de síndrome miasténico congénito de canal lento que presenta debilidad y fatiga lentamente progresivas desde los 8 años. Tras un empeoramiento clínico con piridostigmina, iniciado empíricamente antes de que los resultados de la secuenciación del exoma estuvieran disponibles, se observó una respuesta espectacular y sostenida con efedrina en monoterapia. La secuenciación del exoma reveló una mutación heterocigota de novo en el gen CHRNB1: c.865G>A; p.Val289Met (NM_000747.2). El estudio electromiográfico con estimulación repetitiva en el nervio peroneo mostró una disminución anormal en la amplitud (23,9%) y también la génesis de un segundo potencial de acción muscular compuesto más pequeño después del pico de la onda M principal en los nervios motores mediano, cubital y peroneo. Conclusión. Aunque se han documentado respuestas favorables a agonistas adrenérgicos en asociación con la fluoxetina, ésta representa la primera aportación que documenta una respuesta clínica relevante con efedrina en monoterapia en un paciente con síndrome miasténico congénito de canal lento. Los agonistas adrenérgicos pueden considerarse una opción terapéutica en pacientes con este síndrome.

Hongos y archivos de papel. Caso clínico sobre queratitis fúngica en una paciente documentalista / Fungi and paper-based archives. A case report of fungal keratitis in a documentalist

Pretendemos describir mediante un caso clínico la relación entre los archivos en formato de papel como factor de riesgo para queratitis fúngicas. Para ello, presentamos un caso de una mujer de 32 años, usuaria crónica de lentes de contacto, que se presentó con una queratitis fúngica en su ojo derecho producida por Fusarium spp. mientras trabajaba con libros y documentos antiguos en su profesión como bibliotecaria. Su agudeza visual era de movimiento de manos en el ojo derecho. Fue tratada satisfactoriamente con antibióticos y antifúngicos tópicos, con buena evolución

A description of a case is presented on a relationship between paper-based documents as a risk factor for fungal keratitis. A 32-year-old woman, a long-term contact lens user, presented with fungal keratitis in her right eye caused by Fusarium spp. while working with books and old documents as a librarian. Her visual acuity was hand motion in the right eye. She was satisfactorily treated with topical antifungal and antibiotic agents

Fungi and paper-based archives. A case report of fungal keratitis in a documentalist. / Hongos y archivos de papel. Caso clínico sobre queratitis fúngica en una paciente documentalista.

A description of a case is presented on a relationship between paper-based documents as a risk factor for fungal keratitis. A 32-year-old woman, a long-term contact lens user, presented with fungal keratitis in her right eye caused by Fusarium spp. while working with books and old documents as a librarian. Her visual acuity was hand motion in the right eye. She was satisfactorily treated with topical antifungal and antibiotic agents.

[De novo heterozygous mutation in the MBD5 gene associated with bilateral band heterotopia and polymicrogyria]. / Mutación de novo en heterocigosis en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria.

INTRODUCTION: The aetiology of autosomal dominant mental retardation type 1, also known as pseudo-Angelman, MBD5-associated neurodevelopmental disorder or MBD5 haploinsufficiency, lies in a microdeletion of chromosome 2q23.1 or in a specific alteration of the MBD5 gene, which constitutes the minimum region affected in the aforementioned microdeletion. AIM: To report the case of a girl with a heterozygous de novo mutation in the MBD5 gene associated with bilateral band heterotopia and polymicrogyria. CASE REPORT: We report the case of an 8-year-old girl who was submitted to a developmental follow-up from the age of 18 months after presenting the association of severe intellectual disability and motor delay, lack of language development, segmental hypotonia, a wide forehead and kyphoscoliosis. Magnetic resonance imaging of the brain revealed the presence of a bilateral band heterotopia and parietooccipital polymicrogiria predominant on the left side. In the exome the de novo heterozygous variant c.397+1G>C was detected in the MBD5 gene. CONCLUSION: This is the first observation of a heterozygous mutation in the MBD5 gene associated with a neuronal migration disorder.

TITLE: Mutación de novo en heterocigosis en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria.Introducción. La etiología del retraso mental autosómico dominante 1, también conocido como pseudo-Angelman, trastorno del neurodesarrollo asociado a MBD5 o haploinsuficiencia MBD5, radica en una microdeleción del cromosoma 2q23.1 o en una alteración específica del gen MBD5, que constituye la mínima región afectada en la citada microdeleción. Objetivo. Comunicar el caso de una niña con una mutación heterocigota y de novo en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria. Caso clínico. Niña de 8 años, seguida evolutivamente desde los 18 meses por presentar la asociación de discapacidad intelectual y retraso motor graves, ausencia de desarrollo del lenguaje, hipotonía segmentaria, frente ancha y cifoescoliosis. En la resonancia magnética cerebral se observó la presencia de una heterotopía en banda bilateral y polimicrogiria parietooccipital de predominio izquierdo. En el exoma se detectó la variante de novo c.397+1G>C en heterocigosis en el gen MBD5. Conclusión. Constituye la primera observación con una mutación heterocigota en el gen MBD5 asociada a un trastorno en la migración neuronal.

Experimental generation of a flat-top beam profile in a stable ring cavity.

In this Letter, we present a spatially homogeneous field inside of a ring cavity that was created by combining two transverse modes generated by a single laser through modulation. The interference term between the two modes averages out because of the frequency difference that exists between them, eliminating the need for interferometric control of their relative phase. The use of a ring cavity allows for a large waist for the flat-top profile, big enough to cover the atoms in an atomic trap. The cavity is mechanically and thermally isolated, and the laser light is locked to the cavity using the Pound-Drever-Hall technique. The flat-top profile technique reported here fulfills the vanishing curvature criterion at the center of the profile.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Old and new HLA associations with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily involves the axial skeleton and the sacroiliac joint, but may also affect peripheral joints and entheses. AS susceptibility is clearly attributable to genetic factors and the link between human leukocyte antigen (HLA)-B27 and AS is the strongest association between an HLA class I molecule and a disease. However, there is evidence for the involvement of other, non-B27 factors within the major histocompatibility complex (MHC) in AS susceptibility. MHC class I is clearly the most significant genetic region for the disease, although most of the genetic association of this region is driven by HLA-B27. Moreover, several studies have investigated the MHC class II region and its association with AS. This review summarizes the current findings concerning the MHC genetics of the disease, focusing in particular on the associations of HLA with AS found in different ethnic populations throughout the world, and the possible mechanisms underlying them.

Insuficiencia renal aguda por linfoma de Burkitt renal primario bilateral / Bilateral primary renal Burkitt lymphoma presenting with acute renal failure

Se describe el caso de una niña de 12 años que presenta un cuadro de insuficiencia renal aguda secundaria a infiltración masiva de ambos riñones por un linfoma de Burkitt y que fue diagnosticado por biopsia renal percutánea. Este cuadro cumple los criterios diagnósticos de Malbrain et al para considerarlo un linfoma no Hodgkin primario renal. Se discute el diagnóstico diferencial con otros procesos que se manifiestan con insuficiencia renal aguda y nefromegalia bilateral así como el mecanismo por el cual se produce la insuficiencia renal. En esta paciente es destacable el cuadro clínico de inicio, un cuadro compatible con patología reumática. Se debe tener siempre en cuenta la posibilidad de manifestaciones músculo articulares como patología de inicio en las enfermedades hematopoyéticas (AU)

We report the case of a 12 year-old girl who presented with acute renal failure with massive infiltration in both kidneys due to a Burkitt lymphoma that was diagnosed by percutaneous renal biopsy. This case fulfilled all the diagnostic criteria of Malbrain et al. to be considered as primary renal non-Hodgkin lymphoma. We discuss the differential diagnosis with other processes that present with acute renal failure and bilateral nephromegaly, and the mechanism by which renal failure occurs. It should be emphasised that this patient showed clinical symptoms compatible with rheumatic disease at diagnosis. The possibility of joint and muscle problems should be considered as a sign of onset of hematopoietic disease (AU)

Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection.

Killer immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells and may play an important role in the innate response against infection with viruses such as hepatitis C virus (HCV). We examined whether the different combinations of KIRs with their HLA class I ligands influenced the response to combined treatment (pegylated alpha interferon and ribavirin) of patients infected by HCV. A total of 186 consecutive patients diagnosed with chronic HCV infection were analyzed. Seventy-seven patients exhibited HCV RNA levels at 6 months posttreatment and were called nonresponders (NR), while 109 cleared viral RNA and were named sustained viral responders (SVR). Patients were typed for HLA-B, HLA-Cw, KIR genes, and HCV genotype. In our study, the frequency of the KIR2DL2 allele was significantly increased in NR (P < 0.001; odds ratio [OR] = 1.95), as was the frequency of the KIR2DL2/KIR2DL2 genotype (P < 0.005; OR = 2.52). In contrast, the frequencies of the KIR2DL3 genotype (P < 0.001) and KIR2DL3/KIR2DL3 genotype (P < 0.05; OR = 0.54) were significantly increased in the SVR. Different combinations of KIR2DL2 and KIR2DL3 alleles with their ligands were analyzed. The frequency of the KIR2DL2/KIR2DL2-HLA-C1C2 genotype was significantly increased in the NR (P < 0.01; OR = 3.15). Additionally, we found a higher frequency of the KIR2DL3/KIR2DL3-HLA-C1C1 genotype in the SVR group (P < 0.05; OR = 0.33). These results were not affected by the HCV genotype. In conclusion, patients who carried the KIR2DL2/KIR2DL2-HLA-C1C2 genotype were less prone to respond to treatment. However, the KIR2DL3/KIR2DL3-HLA-C1C1 genotype clearly correlated with a satisfactory response to treatment, defined by the clearance of HCV RNA.

Induction of multiepitopic and long-lasting immune responses against tumour antigens by immunization with peptides, DNA and recombinant adenoviruses expressing minigenes.

The development of immunization strategies to induce strong and multiepitopic T-cell responses against tumour antigens is needed for anti-tumour immunotherapy. However, a common finding after immunization with complex antigens is the preferential induction of immune responses against immunodominant epitopes. In this study, with the aim of inducing multiepitopic responses against several common tumour antigens, we have designed a minigene construct encoding four human leucocyte antigen (HLA)-A2-restricted epitopes belonging to tumour antigens CEA (CEA-691 and CEA-571), MAGE2 (MAGE2-157) and MAGE3 (MAGE3-112), as well as the universal PADRE epitope recognized by T helper lymphocytes. To optimize the activation of immune responses against these epitopes, we have used different antigen formats (short peptides encompassing individual epitopes and DNA plasmids or adenoviral constructs expressing the minigene) in single or combined immunization schedules. A single immunization with either DNA plasmid or recombinant adenovirus induced a monospecific immune response against the immunodominant epitope CEA-571, whereas immunization with the peptide pool induced responses against all epitopes. Combination of peptide priming followed by a boost with the plasmid and the recombinant adenovirus expressing the minigene induced stronger, multi-specific and long-lasting immune responses, overcoming the immunodominance imposed by the main T-cell epitope. Moreover, these combined immunization strategies were able to induce responses that were able to recognize Mel624 HLA-A2+ tumour cells expressing MAGE2. These results suggest that heterologous immunization strategies combining peptides and DNA or recombinant adenoviruses can be useful to broaden the specificity and enhance the efficacy of subunit vaccines.