Bringing Machine-Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration: the Paradigmatic Case of 4-Fluoro-Threonine.

A combined experimental and theoretical study has been carried out on 4-fluoro-threonine, the only naturally occurring fluorinated amino acid. Fluorination of the methyl group significantly increases the conformational complexity with respect to the parent amino acid threonine. The conformational landscape has been characterized in great detail, with special attention given to the inter-conversion pathways between different conformers. This led to the identification of 13 stable low-energy minima. The equilibrium population of so many conformers produces a very complicated and congested rotational spectrum that could be assigned through a strategy that combines several levels of quantum chemical calculations with the principles of machine learning. Twelve conformers out of 13 could be experimentally characterized. The results obtained from the analysis of the intra-molecular interactions can be exploited to accurately model fluorine-substitution effects in biomolecules.

Unveiling the Shape of N-Acetylgalactosamine: A Cancer-Associated Sugar Derivative.

In the present work, we report the first rotational study of N-acetylgalactosamine, a cancer-associated sugar derivative, by means of high-resolution rotational spectroscopy. Two different conformers have been conclusively characterized using broadband Fourier transform microwave spectroscopy coupled with a laser ablation vaporization system. Additionally, we performed a comprehensive analysis of the intramolecular interactions that govern these structures, which allowed us to both characterize the existence of intramolecular hydrogen bond networks that drive the intrinsic conformation panorama of N-acetylgalactosamine and further rationalize the biological role of this aminosugar derivative as part of the Tn antigen.

Rotational spectroscopic study and astronomical search for propiolamide in Sgr B2(N).

CONTEXT: For all the amides detected in the interstellar medium (ISM), the corresponding nitriles or isonitriles have also been detected in the ISM, some of which have relatively high abundances. Among the abundant nitriles for which the corresponding amide has not yet been detected is cyanoacetylene (HCCCN), whose amide counterpart is propiolamide (HCCC(O)NH2). AIMS: With the aim of supporting searches for this amide in the ISM, we provide a complete rotational study of propiolamide from 6 GHz to 440 GHz. METHODS: Time-domain Fourier transform microwave (FTMW) spectroscopy under supersonic expansion conditions between 6 GHz and 18 GHz was used to accurately measure and analyze ground-state rotational transitions with resolved hyperfine structure arising from nuclear quadrupole coupling interactions of the 14N nucleus. We combined this technique with the frequency-domain room-temperature millimeter wave and submillimeter wave spectroscopies from 75 GHz to 440 GHz in order to record and assign the rotational spectra in the ground state and in the low-lying excited vibrational states. We used the ReMoCA spectral line survey performed with the Atacama Large Millimeter/submillimeter Array toward the star-forming region Sgr B2(N) to search for propiolamide. RESULTS: We identified and measured more than 5500 distinct frequency lines of propiolamide in the laboratory. These lines were fitted using an effective semi-rigid rotor Hamiltonian with nuclear quadrupole coupling interactions taken into consideration. We obtained accurate sets of spectroscopic parameters for the ground state and the three low-lying excited vibrational states. We report the nondetection of propiolamide toward the hot cores Sgr B2(N1S) and Sgr B2(N2). We find that propiolamide is at least 50 and 13 times less abundant than acetamide in Sgr B2(N1S) and Sgr B2(N2), respectively, indicating that the abundance difference between both amides is more pronounced by at least a factor of 8 and 2, respectively, than for their corresponding nitriles. CONCLUSIONS: Although propiolamide has yet to be included in astrochemical modeling networks, the observed upper limit to the ratio of propiolamide to acetamide seems consistent with the ratios of related species as determined from past simulations. The comprehensive spectroscopic data presented in this paper will aid future astronomical searches.

[Surgical repair of a thigh muscle herniation with synthetic mesh].

We present the case of a 14-year-old female patient with a big muscle hernia in the thigh after extraction of a fascia lata strip to repair bilateral congenital ptosis. After three weeks, a progressive emergence of a large bulge between the two thigh incisions in a standing position was noticeable, with local discomfort, dull pain on exertion and unsightly ap-pearance that worried the patient. On surgery three months later, a large tear in the fascia lata and muscle herniation was revealed. The fascial tear was debrided and a synthetic mesh was applied. Ten years later, the patient confirmed her continued asymptomatic condition. Muscular hernia of significant size as a consequence of a fascia lata strip harvest is extremely infrequent in adoles-cents. Surgical repair of big muscular hernias in extremities with synthetic mesh, usually used in groin hernia repair, is an infrequent orthopaedic tool but is safe, easy to apply and inexpensive.

Interstellar glycolamide: A comprehensive rotational study and an astronomical search in Sgr B2(N).

CONTEXT: Glycolamide is a glycine isomer and also one of the simplest derivatives of acetamide (e.g., one hydrogen atom is replaced with a hydroxyl group), which is a known interstellar molecule. AIMS: In this context, the aim of our work is to provide direct experimental frequencies of the ground vibrational state of glycolamide in the centimeter-, millimeter- and submillimeter-wavelength regions in order to enable its identification in the interstellar medium. METHODS: We employed a battery of state-of-the-art rotational spectroscopic techniques in the frequency and time domain to measure the frequencies of glycolamide. We used the spectral line survey named Exploring Molecular Complexity with ALMA (EMoCA), which was performed toward the star forming region Sgr B2(N) with ALMA to search for glycolamide in space. We also searched for glycolamide toward Sgr B2(N) with the Effelsberg radio telescope. The astronomical spectra were analyzed under the local thermodynamic equilibrium approximation. We used the gas-grain chemical kinetics model MAGICKAL to interpret the results of the astronomical observations. RESULTS: About 1500 transitions have been newly assigned up to 460 GHz to the most stable conformer, and a precise set of spectroscopic constants was determined. Spectral features of glycolamide were then searched for in the prominent hot molecular core Sgr B2(N2). We report the nondetection of glycolamide toward this source with an abundance at least six and five times lower than that of acetamide and glycolaldehyde, respectively. Our astrochemical model suggests that glycolamide may be present in this source at a level just below the upper limit, which was derived from the EMoCA survey. We could also not detect the molecule in the region's extended molecular envelope, which was probed with the Effelsberg telescope. We find an upper limit to its column density that is similar to the column densities obtained earlier for acetamide and glycolaldehyde with the Green Bank Telescope.

[Slipped capital femoral epiphysis in an ambulant patient with spastic cerebral palsy. A long-term evolution].

We report the case of a boy aged 13 years and 9 months, with predominantly right-sided spastic tetraparesis, who could walk with assistance, GMFCS III, phenotype consistent with adiposogenital syndrome. He presented a 4-week history of left-sided limp without pain, radiologically classified as a stable, chronic slipped capital femoral epiphysis (SCFE) with mild slippage (<30º) on the Southwick classification. In situ fixation of the hip was performed using a full-headed screw, followed by six weeks of rest. Twelve years since the intervention, the patient remains asymptomatic with no clinical or radiological changes. SCFE in patients with cerebral palsy, while highly unusual, is possible. A high level of suspicion is required for diagnosing it. We would suggest ruling out the appearance of SCFE during surveillance screening of patients with cerebral palsy, =?10 years-old, particularly in obese individuals with or without adiposogenital phenotype and limited ability to communicate verbally.

A rotational study of the AlaAla dipeptide.

Herein, we present the first rotational study of the AlaAla dipeptide, brought into the gas phase by laser ablation. Two different structures have been unveiled in the isolated environment of a supersonic expansion by Fourier transform microwave spectroscopy. These structures have been identified through their rotational and 14N quadrupole coupling constants. The flexibility of the -NH2 and -COOH ends allows the formation of strong intramolecular interactions giving rise to five- and seven-membered ring configurations.

Gas-Phase Conformational Map of the Amino Acid Isovaline.

Four conformers of the non-proteinogenic α-amino acid isovaline, vaporized by laser ablation, are characterized by Fourier-transform microwave techniques in a supersonic expansion. The comparison between the experimental rotational and 14 N nuclear quadrupole coupling constants and the ab initio calculated ones provides conclusive evidence for the identification of the conformers. The most stable species is stabilized by an N-H⋅⋅⋅O =C intramolecular hydrogen bond and a cis-COOH interaction, whereas the higher-energy conformers exhibit an N⋅⋅⋅H-O intramolecular hydrogen bond and trans-COOH, as in other aliphatic amino acids. The spectroscopic data herein reported can be used for the astrophysical purpose in a possible detection of isovaline in space.

Acute haematogenous septic arthritis of a lumbar facet joint in an otherwise healthy adolescent.

Facet joint septic arthritis is a rare cause of spinal infection in children with only four cases reported. The transmission pathway is believed to be haematogenous in 72% of cases. The authors present the case of a 13-year-old boy hospitalised for acute lumbosciatalgia, limp and fever, with pain upon palpation of the paravertebral muscles, a positive Laségue signal and elevated serum inflammatory markers. The initial lumbar computerised tomography (TC) scan revealed no abnormalities in the interapophyseal joints. After improving on treatment with analgesics and antibiotics, he was readmitted one month later due to clinical deterioration, and septic arthritis of left facet joint L3-L4 was confirmed by magnetic resonance imaging (MRI). The patient experienced a full recovery after treatment with systemic antibiotics (cefotaxime-cloxacilin) and rehabilitation. A high index of suspicion is necessary to diagnose this localization as a manifestation of lumbosciatalgia and/or limp in children. CT-scan or, preferably, MRI is mandatory to confirm this diagnosis.

Distal radial torus fracture in an adult. A new type of occult wrist fracture?

Torus or buckle fractures typically affect children who have suffered indirect minor wrist injuries. They are axial compression-type metaphyseal fractures of cortical and cancellous bone, which are stable and their treatment therefore consists in immobilisation of the joint for three to four weeks. We present an atypical case of distal radius torus fracture in a 19-year-old adult male, which has not been previously reported in adults and can be considered a new type of occult fracture. Knowledge of this possibility is mandatory to be able to make a differential diagnosis of wrist sprain in adults, and avoid performing superfluous complementary tests due to the persistence of pain and functional incapacity.

Elucidating the multiple structures of pipecolic acid by rotational spectroscopy.

The complex conformational space of the non-proteinogenic cyclic amino acid pipecolic acid has been explored in the gas phase for the first time. Solid pipecolic acid samples were vaporized by laser ablation and expanded in a supersonic jet where the rotational spectral signatures owing to nine different conformers were observed by Fourier transform microwave spectroscopy. All species were identified by comparison of the experimental rotational and nuclear quadrupole coupling constants with those predicted theoretically. Observation of type-III conformers, leading to a difference when compared against the conformational behavior of the analog amino acid proline, has been interpreted by an increment in steric hindrance when increasing the number of carbons present in the ring.

Laboratory rotational spectrum and astronomical search for methoxyacetaldehyde.

CONTEXT: Methoxyacetaldehyde belongs to a group of structural isomers with the general formula C3H6O2, of which methyl acetate and ethyl formate are known interstellar molecules. Rotational data available for methoxyacetaldehyde are limited to 40 GHz, which makes predictions at higher frequencies rather uncertain. AIMS: The aim of this work is to provide accurate experimental frequencies of methoxyacetaldehyde in the millimeter-wave region to support its detection in the interstellar medium. METHODS: The rotational spectrum of methoxyacetaldehyde was recorded at room-temperature from 75 to 120 GHz and from 170 to 310 GHz using the millimeter-wave spectrometer in Valladolid. Additional measurements were also performed at conditions of supersonic expansion from 6 to 18 GHz. The assigned rotational transitions were analyzed using the S -reduced semirigid-rotor Hamiltonian. RESULTS: We newly assigned over 1000 lines for the most stable conformer of methoxyacetaldehyde in its ground state and five lowest excited vibrational states, and precise sets of spectroscopic constants were obtained. We searched for spectral features of methoxyacetaldehyde in the high-mass star-forming regions Orion KL and Sagittarius B2, as well as in the cold dark cloud Barnard 1 (B1-b). No lines belonging to methoxyacetaldehyde were detected above the detection limit of our data. We provide upper limits to the methoxyacetaldehyde colum density in these sources.

The effect of N-methylation on the conformational landscape of alanine: the case of N-methyl-l-alanine.

The non-proteinogenic amino acid N-methyl-l-alanine has been brought into the gas phase using laser ablation techniques and studied by high resolution chirped pulse and molecular-beam Fourier transform microwave spectroscopies coupled to supersonic expansion. Four conformers showing the three types of hydrogen bond interactions I (NHO[double bond, length as m-dash]C), II (OHN) and III (N-HO-H) have been unambiguously identified, based on the comparison of the experimental rotational and 14N nuclear quadrupole constants with the calculated ab initio values. The observation of a type III conformer evidences the role of methyl groups in both sides to impose the steric hindrance, precluding the relaxation from type III to type I conformers and explains the responsibility for the unique conformational landscape observed in the case of NMA.

The role of amino acid side chains in stabilizing dipeptides: the laser ablation Fourier transform microwave spectrum of Ac-Val-NH2.

The steric effects imposed by the isopropyl group of valine in the conformational stabilization of the capped dipeptide N-acetyl-l-valinamide (Ac-Val-NH2) have been studied by laser ablation molecular beam Fourier transform microwave (LA-MB-FTMW) spectroscopy. The rotational and quadrupole coupling constants of the two 14N nuclei determined in this work show that this dipeptide exists as a mixture of C7 and C5 conformers in the supersonic expansion. The conformers are stabilized by a C[double bond, length as m-dash]OH-N intramolecular hydrogen bond closing a seven- or a five-membered ring, respectively. The observation of both conformers is in good agreement with previous results on the related dipeptides containing different residues, confirming that the polarity/non-polarity of the side chains of the amino acid is responsible for the conformational locking/unlocking. The voluminous isopropyl group is not able to prevent the less stable C5 conformer from forming but it destabilizes the C[double bond, length as m-dash]OH-N interaction.

Enfermedad de Blount: a propósito de un caso / Blount disease: a case report

La enfermedad de Blount o tibia vara es una alteración del desarrollo que afecta al cartílago de crecimiento proximal de la tibia. Es una entidad poco frecuente y de probable origen multifactorial, cuya etiología no está aclarada. Provoca una deformidad progresiva con un arqueamiento de las extremidades inferiores en forma de genu varo. En la variante precoz es más frecuente la afectación bilateral por lo que en los casos leves puede ser difícil diferenciar del genu varo fisiológico. Presentamos el caso de una niña de 15 meses de origen africano que presenta un genu varo bilateral progresivo. Tras un seguimiento clínico y radiológico precisó finalmente corrección quirúrgica de la deformidad (AU)

Blount disease is a developmental disorder that affects the proximal growth cartilage of the tibia. It is a rare entity of probable multifactorial origin whose etiology is not clear. It causes a progressive deformity with a bowing of the lower limbs in the form of a genu varum. In the early variant, bilateral involvement is more frequent, so in mild cases it may be difficult to differentiate between the physiological variant. We present the case of a 15-month-old girl of African origin, who has a progressive bilateral genu varum. After a clinical and radiological follow-up, he finally needed surgical correction of the deformity (AU)

Psychosine variants as antigens for natural killer T cells.

Natural killer T (NKT) cells play a central role in the interface between innate and adaptive immunity, and alpha-galactosylceramide was recently shown to be an endogenous antigen for these cells. The source of alpha-galactosylceramide has not yet been determined; however, in vivo degradation of alpha-galactosylceramide involves generation of alpha-psychosine (alpha-galactosylsphingosine). Alpha-psychosine stimulates cytokine release from NKT cells and constitutes an endogenous antigen for these cells. Alpha-psychosine contains a single lipid chain, while most antigens for NKT cells have two lipid chains, and we have investigated if other glycolipids with one lipid chain, derived from know antigens for NKT cells, stimulate cytokine release from NKT cells. Only psychosine variants derived from the most potent NKT cell antigens cause stimulation, and this stimulation occurs in vitro as well as in vivo. Truncated forms of weak antigens for NKT cells are not stimulatory.

Transporte pediátrico y neonatal en España, Portugal y Latinoamérica / Pediatric and neonatal transport in Spain, Portugal and Latin America

OBJETIVO: Estudiar la organización del transporte interhospitalario pediátrico y neonatal en la península ibérica y Latinoamérica. DISEÑO: Estudio observacional prospectivo mediante una encuesta enviada por correo electrónico con preguntas sobre el sistema de transporte nacional, regional y local, el tipo y vehículo de traslado, el material y el personal y su formación. Ámbito: Responsables pediátricos de hospitales de España, Portugal y Latinoamérica. RESULTADOS: Se analizaron 117 encuestas provenientes de 15 países. De ellas, 55 (47%) procedían de 15 comunidades autónomas de España y el resto de Portugal y de 13 países latinoamericanos. Muy pocas regiones y ciudades tienen un sistema de transporte pediátrico y neonatal específico. El transporte solo está unificado en las comunidades españolas de Baleares y Cataluña y en Portugal. En Chile el sistema de transporte es mixto, pediátrico y del adulto. Solo un 51,4% de los hospitales tiene un sistema de formación del personal de transporte, y solo en el 36,4% la formación es específica en transporte pediátrico. En España y Portugal los sistemas de transporte son fundamentalmente públicos, mientras que en Latinoamérica coexisten sistemas públicos y privados. Los equipos de transporte de la península ibérica tienen más material pediátrico y neonatal y reciben más formación en transporte pediátrico que los de Latinoamérica. CONCLUSIONES: Existe una gran variabilidad en la organización del transporte pediátrico en cada país y región. En la mayoría de los países y ciudades no existe un sistema unificado y específico de transporte pediátrico con un personal cualificado y un material de traslado específico

OBJECTIVE: To study the organization of inter-hospital transport of pediatric and neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational study was performed. An on-line survey was sent by email including questions about characteristics of national, regional and local health transport systems, vehicles, material, and composition of the transport team and their training. SETTING: Hospital pediatric healthcare professionals treating children in Spain, Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from Portugal and 13 Latin American countries. The inter-hospital transport of pediatric patients is unified only in the Spanish regions of Baleares and Cataluña and in Portugal. Chile has a mixed unified transport system for pediatric and adult patients. Only 51.4% of responders have an educational program for the transport personnel, and only in 36.4% of them the educational program is specific for pediatric patients. In Spain and Portugal the transport is executed mostly by public entities, while in Latin America public and private systems coexist. Specific pediatric equipment is more frequent in the transport teams in the Iberian Peninsula than in Latin American teams. The specific pediatric transport training is less frequent for teams in Latin America than on Spain and Portugal. CONCLUSIONS: There is a great variation in the organization of children transport in each country and region. Most of countries and cities do not have unified and specific teams of pediatric transport, with pediatric qualified personnel and specific material

Pediatric and neonatal transport in Spain, Portugal and Latin America. / Transporte pediátrico y neonatal en España, Portugal y Latinoamérica.

OBJECTIVE: To study the organization of inter-hospital transport of pediatric and neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational study was performed. An on-line survey was sent by email including questions about characteristics of national, regional and local health transport systems, vehicles, material, and composition of the transport team and their training. SETTING: Hospital pediatric healthcare professionals treating children in Spain, Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from Portugal and 13 Latin American countries. The inter-hospital transport of pediatric patients is unified only in the Spanish regions of Baleares and Cataluña and in Portugal. Chile has a mixed unified transport system for pediatric and adult patients. Only 51.4% of responders have an educational program for the transport personnel, and only in 36.4% of them the educational program is specific for pediatric patients. In Spain and Portugal the transport is executed mostly by public entities, while in Latin America public and private systems coexist. Specific pediatric equipment is more frequent in the transport teams in the Iberian Peninsula than in Latin American teams. The specific pediatric transport training is less frequent for teams in Latin America than on Spain and Portugal. CONCLUSIONS: There is a great variation in the organization of children transport in each country and region. Most of countries and cities do not have unified and specific teams of pediatric transport, with pediatric qualified personnel and specific material.

[Idiopatic chondrolysis of the hip. Long-term follow-up of a case]. / Condrolisis idiopática de cadera. Evolución a largo plazo.

Idiopathic chondrolysis of the hip is a very rare disease occurring during adolescence. Pain and limp are the most common symptoms and are a consequence of an accelerated loss of the articular cartilage with a lower range of move-ment producing rigidity in the last instance. The natural history is unpredictable and varies between complete and spon-taneous recovery and the ankylosis. The current recommended treatment is conservative, restricting the surgical option for residual stiffness. A clinical case of an eleven year old patient is presented. He consulted for a 2 year, torpid course of left groin pain with limp and rigidity. He received treatment with rest, discharge, analgesics and rehabilitation without any improvement initially. He was treated conservatively with NSAIDS, extremity discharge periods, soft traction in the hospital and at home and rehabilitation, recovering mobility and normal gait 6 years after the beginning of the symptoms. Twelve years after the onset of the symptoms the patient leads a normal life without symptoms and has a symmetric range of motion of both hips.

Condrolisis idiopática de cadera. Evolución a largo plazo / Idiopatic chondrolysis of the hip. Long-term follow-up of a case

La condrolisis idiopática de cadera es una rara condición que se presenta durante la adolescencia. Se caracteriza por dolor y cojera producidos por una pérdida acelerada del cartílago articular con una disminución del grado de movilidad llegando a rigidez. La historia va desde la resolución espontánea completa a la anquilosis. El tratamiento recomendado actualmente es el conservador. Se presenta el caso clínico de un paciente de 11 años de edad con un cuadro clínico de 2 años de evolución tórpida de dolor inguinal izquierdo acompañado de cojera y rigidez. Se instauró reposo, descarga, analgésicos y rehabilitación sin mejoría inicial. Posteriormente recibió tratamiento conservador con AINE, periodos de descarga de la extremidad, tracción blanda hospitalaria, tracción ambulatoria nocturna y rehabilitación, recuperando la movilidad y marcha normal 6 años después del inicio de los síntomas. Catorce años más tarde el paciente hace una vida normal, asintomático y con movilidad simétrica de ambas caderas (AU)

Idiopathic chondrolysis of the hip is a very rare disease occurring during adolescence. Pain and limp are the most common symptoms and are a consequence of an accelerated loss of the articular cartilage with a lower range of movement producing rigidity in the last instance. The natural history is unpredictable and varies between complete and spontaneous recovery and the ankylosis. The current recommended treatment is conservative, restricting the surgical option for residual stiffness. A clinical case of an eleven year old patient is presented. He consulted for a 2 year, torpid course of left groin pain with limp and rigidity. He received treatment with rest, discharge, analgesics and rehabilitation without any improvement initially. He was treated conservatively with NSAIDS, extremity discharge periods, soft traction in the hospital and at home and rehabilitation, recovering mobility and normal gait 6 years after the beginning of the symptoms. Twelve years after the onset of the symptoms the patient leads a normal life without symptoms and has a symmetric range of motion of both hips (AU)