Evaluating the daily modulation of FADD and related molecular markers in different brain regions in male rats.

Fas-Associated protein with Death Domain (FADD), a key molecule controlling cell fate by balancing apoptotic versus non-apoptotic functions, is dysregulated in post-mortem brains of subjects with psychopathologies, in animal models capturing certain aspects of these disorders, and by several pharmacological agents. Since persistent disruptions in normal functioning of daily rhythms are linked with these conditions, oscillations over time of key biomarkers, such as FADD, could play a crucial role in balancing the clinical outcome. Therefore, we characterized the 24-h regulation of FADD (and linked molecular partners: p-ERK/t-ERK ratio, Cdk-5, p35/p25, cell proliferation) in key brain regions for FADD regulation (prefrontal cortex, striatum, hippocampus). Samples were collected during Zeitgeber time (ZT) 2, ZT5, ZT8, ZT11, ZT14, ZT17, ZT20, and ZT23 (ZT0, lights-on or inactive period; ZT12, lights-off or active period). FADD showed similar daily fluctuations in all regions analyzed, with higher values during lights off, and opposite to p-ERK/t-ERK ratios regulation. Both Cdk-5 and p35 remained stable and did not change across ZT. However, p25 increased during lights off, but exclusively in striatum. Finally, no 24-h modulation was observed for hippocampal cell proliferation, although higher values were present during lights off. These results demonstrated a clear daily modulation of FADD in several key brain regions, with a more prominent regulation during the active time of rats, and suggested a key role for FADD, and molecular partners, in the normal physiological functioning of the brain's daily rhythmicity, which if disrupted might participate in the development of certain pathologies.

Inpatient Rehabilitation Falls: Comparing Patients With Traumatic Brain Injury Versus Patients With Stroke.

BACKGROUND: Cognitively impaired neurological rehabilitation inpatients are at an increased risk for falls; yet, little is known regarding fall risk of different groups, such as stroke versus traumatic brain injury. OBJECTIVES: To determine if rehabilitation patients' fall characteristics differ for patients with stroke versus patients with traumatic brain injury. METHODS: This retrospective observational cohort study evaluates inpatients with stroke or traumatic brain injury admitted to a rehabilitation center in Barcelona, Spain, between 2005 and 2021. We assessed independence in daily activities with the Functional Independence Measure. We compared fallen versus nonfallen patients' features and examined the association between time to first fall and risk using Cox proportional hazards models. RESULTS: A total of 1,269 fall events were experienced by 898 different patients with traumatic brain injury ( n = 313; 34.9%) and stroke ( n = 585; 65.1%). A higher proportion of falls for patients with stroke occurred while performing rehabilitation activities (20.2%-9.8%), whereas falls were significantly higher for patients with traumatic brain injury during the night shift. Fall timing revealed completely different behaviors (stroke vs. traumatic brain injury), for example, an absolute peak at 6 a.m. due to young male traumatic patients. Nonfallen patients ( n = 1,363; 78.2%) were younger, with higher independence in daily activities scores, and having a larger time since injury to admission; all three were significant fall predictors. CONCLUSIONS: Patients with traumatic brain injury and stroke showed different fall behaviors. Knowledge of fall patterns and characteristics in the inpatient rehabilitation setting can help design management protocols to mitigate their risk.

First splicing variant in HECW2 with an autosomal recessive pattern of inheritance and associated with NDHSAL.

We report the clinical and genetic features of a Caucasian girl who presented a severe neurodevelopmental disorder with drug-resistant epilepsy, hypotonia, severe gastro-esophageal reflux and brain magnetic resonance imaging anomalies. WES uncovered a novel variant in homozygosis (g.197092814_197092824delinsC) in HECW2 gene that encodes the E3 ubiquitin-protein ligase HECW2. This protein induces ubiquitination and is implicated in the regulation of several important pathways involved in neurodevelopment and neurogenesis. Furthermore, de novo heterozygous missense variants in this gene have been associated with neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL). The homozygous variant of our patient disrupts the splice donor site of intron 22 and causes the elimination of exon 22 (r.3766_3917+1del) leading to an in-frame deletion of the protein (p.Leu1256_Trp1306del). Functional studies showed a twofold increase of its RNA expression, while the protein expression level was reduced by 60%, suggesting a partial loss-of-function mechanism of pathogenesis. Thus, this is the first patient with NDHSAL caused by an autosomal recessive splicing variant in HECW2.

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment.

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function.

MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.

Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.

Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes' expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practice.

Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants.

We report the clinical, biochemical and genetic findings from a Spanish boy of Caucasian origin who presented with fever-dependent RALF (recurrent acute liver failure) and osteogenesis imperfecta (OI). Whole-exome sequencing (WES) uncovered two compound heterozygous variants in NBAS (c.[1265 T > C];[1549C > T]:p.[(Leu422Pro)];[(Arg517Cys)]), and a heterozygous variant in P4HB (c.[194A > G];[194=]:p.[(Lys65Arg)];[(Lys65=)]) that was transmitted from the clinically unaffected mother who was mosaic carrier of the variant. Variants in NBAS protein have been associated with ILFS2 (infantile liver failure syndrome-2), SOPH syndrome (short stature, optic nerve atrophy, and Pelger-Huët anomaly syndrome), and multisystem diseases. Several patients showed clinical manifestations affecting the skeletal system, such as osteoporosis, pathologic fractures and OI. Experiments in the patient's fibroblasts demonstrated that mutated NBAS protein is overexpressed and thermally unstable, and reduces the expression of MGP, a regulator of bone homeostasis. Variant in PDI (protein encoded by P4HB) has been associated with CLCRP1 (Cole-Carpenter syndrome-1), a type of severe OI. An increase of COL1A2 protein retention was observed in the patient's fibroblasts. In order to study if the variant in P4HB was involved in the alteration in collagen trafficking, overexpression experiments of PDI were carried out. These experiments showed that overexpression of mutated PDI protein produces an increase in COL1A2 retention. In conclusion, these results corroborate that the variants in NBAS are responsible for the liver phenotype, and demonstrate that the variant in P4HB is involved in the bone phenotype, probably in synergy with NBAS variants.

Blood transfusion activity in a general hospital during the COVID-19 pandemic.

BACKGROUND: The COVID-19 outbreak has affected almost all hospital departments, including transfusion services. However, the demand for transfusions in a general hospital designated to deal with COVID-19 patients has not been analysed before. STUDY DESIGN AND METHODS: A retrospective study was conducted to evaluate blood transfusion practices from 15 March to 14 April 2020 at Hospital Universitario Infanta Leonor (Madrid, Spain). During this month, with few exceptions, the hospital became a 'COVID-19' centre. In addition, transfusion rates during this time frame and the same period over the last 4 years were compared. RESULTS: From 15 March to 14 April 2020, only 254 blood components were transfused, resulting in a 49·3% reduction over the previous year. Interestingly, in critically ill patients, the red blood cell (RBC) transfusion/bed ratio significantly decreased during this period (0·92) compared to the same ratio over the past 4 years (2·70) (P = 0·02). Of note, 106 blood components (95 RBC; 11 platelet concentrates) were transfused to only 36 out of 1348 COVID-19 patients (2·7%). The main reason for RBC transfusion in COVID-19 patients was a previous underlying disease (44%) followed by bleeding (25%) and inflammatory anaemia (25%). CONCLUSION: This is the first study to report a decrease in blood transfusions during the COVID-19 pandemic in a general hospital and especially in the intensive care unit. The results of this study suggest that COVID-19 does not generally induce transfusion requiring anaemia, being the main causes for transfusion in these patients underlying conditions or bleeding.

Unexpected Cause of Persistent Microcytosis and Neurological Symptoms in a Child: Niemann-Pick Disease Type C.

Atypical microcytic anemias are rare diseases of iron/heme metabolism that can be diagnostically challenging. We report the case of a 2-year-old twin boy with neurodevelopmental delay and persistent microcytosis in whom atypical microcytic anemias was initially suspected. He had low blood iron and transferrin saturation with normal/high ferritin despite iron therapy. Hemoglobinopathies were excluded by conventional/DNA studies. Hepcidin was high but iron-refractory-iron-deficiency anemia was ruled out by a genetic panel. Bone marrow aspiration revealed foamy cells and iron depletion. A genetic study confirmed the diagnosis of Niemann-Pick disease type C which was finally considered the origin of microcytosis through anemia of chronic disease.

Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy.

OBJECTIVE: Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. METHODS: We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. RESULTS: In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. INTERPRETATION: This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.

MAST1 variant causes mega-corpus-callosum syndrome with cortical malformations but without cerebellar hypoplasia.

We report the case of a Caucasian Spanish origin female who showed severe psychomotor developmental delay, hypotonia, strabismus, epilepsy, short stature, and poor verbal language development. Brain magnetic resonance imaging scans showed thickened corpus callosum, cortical malformations, and dilated and abnormal configuration of the lateral ventricles without hydrocephalus. Whole-exome sequence uncovered a de novo variant in the microtubule associated serine/threonine kinase 1 gene (MAST1; NM_014975.3:c.1565G>A:p.(Gly522Glu)) that encodes for the MAST1. Only 12 patients have been identified worldwide with 10 different variants in this gene: six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; two patients with microcephaly and cerebellar hypoplasia; two patients with autism, one patient with diplegia, and one patient with microcephaly and dysmorphism. Our patient shows a new phenotypic subtype defined by mega-corpus-callosum syndrome with cortical malformations without cerebellar hypoplasia. In conclusion, our data expand the phenotypic spectrum associated to MAST1 gene variants.

Perioperative management of children with urea cycle disorders.

BACKGROUND: Urea cycle disorders are congenital metabolism errors that affect ammonia elimination. Clinical signs and prognosis are strongly influenced by peak ammonia levels. Numerous triggers associated with metabolic decompensation have been described with many of them, including fasting or stress, being related to the perioperative period. AIMS: We aimed to assess perioperative complications in pediatric patients with urea cycle disorders requiring general anesthesia in our center. METHODS: We reviewed the clinical history of all the pediatric patients with a confirmed urea cycle disorders diagnosis requiring surgery or a diagnostic procedure with anesthesia between January 2002 and June 2018. RESULTS: We included 33 operations (major surgery, minor surgery, and diagnostic procedures) carried out on 10 patients via different anesthetic techniques. We observed the following complications: intraoperative hyperglycemia in one case, postoperative vomiting in eight cases, and slightly increased postoperative ammonia levels (54, 59, and 69 µmol/L) with normal preoperative levels in three cases without associated metabolic decompensation. There were two cases of perioperative hyperammonemia (72 and 69 µmol/L) secondary to preoperative metabolic decompensation (137 and 92 µmol/L) with the levels progressively dropping and normalizing in the first 24-48 hours, respectively. CONCLUSIONS: Procedures under anesthesia on pediatric patients with urea cycle diseases should be performed by experienced multidisciplinary teams at specialized centers. Perioperative management focused on avoiding catabolism (especially during fasting) and monitoring signs associated with metabolic decompensation to allow for its early treatment should be included in routine anesthetic techniques for children with urea cycle disorders.

Orbital emphysema after transcanalicular laser-assisted dacryocystorhinostomy treated with needle decompression.

Orbital emphysema is an abnormal presence of air in the orbit. It usually arises after blunt trauma or periorbital surgery. When it occurs after dacryocystorhinostomy, usually it is reported as a benign condition. We present a case of a severe orbital emphysema secondary to transcanalicular diode laser-assisted dacryocystorhinostomy. The day after the surgery, the examination revealed crepitant periorbital swelling, general restriction of extraocular motility, visual loss and intraocular pressure of more than 70 mmHg. A computed tomography showed a massive orbital emphysema. An emergency decompression, using a 25-gauge needle attached to an empty syringe lacking a plunger was performed, achieving a quick decrease of intraocular pressure and pain and swelling improvement. Then, in this case, orbital decompression by passive airflow using a needle without a plunger was an effective treatment method to resolve a serious orbital emphysema after transcanalicular laser-assisted dacryocystorhinostomy.

Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.

Etiology, seizure type, and prognosis of epileptic seizures in the emergency department.

Epileptic seizures are a common reason for emergency department (ED) admittance. We aimed to describe the etiological distribution of epileptic seizures and the relationships between etiology and semiology in patients admitted to the emergency room, and to identify early prognostic factors for recurrence and mortality. METHODS: A retrospective observational study was conducted in adult patients consecutively attended in the emergency room with epileptic seizures over a 2-year period. We recorded data on the etiological and syndromic classification of the seizure, and on recurrence and mortality at 1 year of follow-up. RESULTS: In total, 289 patients were included. Mean age was 55.9 (±21.9 years). There were 38.6% with a previous diagnosis of epilepsy and 49.8% with new-onset seizures. Among structural epilepsies, a vascular etiology was the most common overall (28.3%) but particularly in elderly (>65 years) patients (50.9%), followed by brain tumors (15.5%). In both etiologies, most patients presented with nonconvulsive seizures. Seizure recurrence during follow-up was reported in 37.1% and was most common in patients with symptomatic remote seizures (50 patients, 41%). Brain tumors (odds ratio (OR): 5.1, confidence interval (CI): 1.7-11.8; p < 0.01), younger age (OR: 0.9, CI: 0.97-0.99; p < 0.05), and a previous diagnosis of epilepsy (OR: 3.5, CI: 1.9-6.3; p < 0.01) were independent predictors of recurrence. Overall mortality was 8.6%. Symptomatic epilepsy was an independent predictor of mortality (hazard ratio (HR): 6.3, CI 1.4-23.4; p < 0.05). CONCLUSIONS: The most common etiologies of seizures in patients admitted to the ED are seizures of unknown cause and vascular disorder-related seizures. Seizures are more likely to recur in younger patients with a tumor whereas symptomatic epilepsy is associated with a higher risk of death at a 1-year follow-up.

Protein matrices ensure safe and functional delivery of rosmarinic acid from marjoram (Origanum majorana) extracts.

BACKGROUND: To understand the interactions between carriers and functional ingredients is crucial when designing delivery systems, to maximize bioefficacy and functionality. In this study, two different protein matrices were evaluated as means to protect the extract isolated from marjoram leaves (Origanum majorana), casein micelles from fresh skim milk and soy protein isolate (SPI). RESULTS: Marjoram extract was obtained from pressurization of ethanol and water solvent. Protein dispersions of casein and SPI (5 g L-1 each) with or without marjoram extract (0.1-3 mg mL-1 ) were prepared and homogenized. The physicochemical characterization of charge and entrapment efficiency were conducted. The results demonstrated that entrapment efficiency was highly dependent on the carrier itself where SPI formulations showed 20% higher affinity when compared to casein micelles. To investigate the physiological behaviour of the marjoram-protein dispersions, human macrophages were employed. A non-specific inflammatory response of macrophages stimulated with bacterial lipopolysaccharide was measured for TNF-α, IL-1ß and IL-6 cytokine secretion. CONCLUSION: Casein and SPI protein formulations warranted high bioefficacy of marjoram extract, showing their potential as safe carriers. © 2018 Society of Chemical Industry.

Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NR2F1 gene mutation.

We report the clinical and biochemical findings from a patient who presented with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal-dominant disorder characterized by optic atrophy, developmental delay and intellectual disability. In addition, the patient also displays hypotonia, stroke-like episodes, and complex IV deficiency of the mitochondrial respiratory chain. Whole-exome sequencing (WES) uncovered a novel heterozygous mutation in the NR2F1 gene (NM_005654:c.286A>G:p.Lys96Glu) that encodes for the COUP transcription factor 1 protein (COUP-TF1). Loss-of-function mutations in this protein have been associated with BBSOAS, and a luciferase reporter assay showed that this variant, in the zinc-finger DNA-binding domain (DBD) of COUP-TF1 protein, impairs its transcriptional activity. The additional features of this patient are more related with mitochondrial diseases that with BBSOAS, indicating a mitochondrial involvement. Finally, our data expand both the genetic and phenotypic spectrum associated with NR2F1 gene mutations.

Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.

OBJECTIVE: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. METHODS: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. RESULTS: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days-33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic "putaminal eye" was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. INTERPRETATION: MEGDHEL syndrome is a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004-1015.

Efficient directly emitting high-power Tb3+:LiLuF4 laser operating at 587.5 nm in the yellow range.

We present, to the best of our knowledge, the most efficient solid-state laser directly emitting in the yellow spectral range. Without any nonlinear conversion steps, a Tb3+:LiLuF4 laser operates at a wavelength of 587.5 nm with an output power of 0.5 W and a record-high slope efficiency of 25% with respect to the absorbed pump power at 486.2 nm. Despite the detrimental influence of 4f-excited state absorption, this efficiency is comparable to those obtained by complex nonlinear methods to generate yellow laser emission. Our approach, in combination with the progress in laser diodes at the required pump wavelength, paves the way for the development of cost-efficient, robust, and easily manageable diode-pumped yellow laser sources.

Spectroscopic properties and continuous-wave deep-red laser operation of Eu3+-doped LiYF4.

Eu3+-doped LiYF4 is reexamined as a laser material for the visible spectral region. Polarized absorption and emission cross sections as well as the fluorescence lifetime are determined. Branching ratios and radiative lifetime are calculated within the theory of 4f-4f transition intensities, which takes into account the influence of an excited configuration of the opposite parity 4fN-15d. Continuous-wave laser operation at 702 nm is demonstrated with a maximum output power of 15 mW and a slope efficiency of 4.6% under pumping with a frequency-doubled Ti:sapphire laser at 393.5 nm.