High-speed fixed-target serial virus crystallography.

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities.

A novel method for resonant inelastic soft X-ray scattering via photoelectron spectroscopy detection.

A method for measuring resonant inelastic X-ray scattering based on the conversion of X-ray photons into photoelectrons is presented. The setup is compact, relies on commercially available detectors, and offers significant flexibility. This method is demonstrated at the Linac Coherent Light Source with ∼0.5 eV resolution at the cobalt L3-edge, with signal rates comparable with traditional grating spectrometers.

The X-ray Pump-Probe instrument at the Linac Coherent Light Source.

The X-ray Pump-Probe instrument achieves femtosecond time-resolution with hard X-ray methods using a free-electron laser source. It covers a photon energy range of 4-24 keV. A femtosecond optical laser system is available across a broad spectrum of wavelengths for generating transient states of matter. The instrument is designed to emphasize versatility and the scientific goals encompass ultrafast physical, chemical and biological processes involved in the transformation of matter and transfer of energy at the atomic scale.

The X-ray Correlation Spectroscopy instrument at the Linac Coherent Light Source.

The X-ray Correlation Spectroscopy instrument is dedicated to the study of dynamics in condensed matter systems using the unique coherence properties of free-electron lasers. It covers a photon energy range of 4-25 keV. The intrinsic temporal characteristics of the Linac Coherent Light Source, in particular the 120 Hz repetition rate, allow for the investigation of slow dynamics (milliseconds) by means of X-ray photon correlation spectroscopy. Double-pulse schemes could probe dynamics on the picosecond timescale. A description of the instrument capabilities and recent achievements is presented.

Pharmacological management of children with short stature: the role of aromatase inhibitors.

OBJECTIVE: To review the use of aromatase inhibitors, a novel treatment strategy for patients with short stature, which aims at delaying bone age advancement. Skeletal maturation is estrogen-dependent even in male children. SOURCES: We performed a MEDLINE search of studies published in the last 10 years, including aromatase, short stature, and early puberty as keywords. The most informative articles on indications, dosages, treatment schedules, and side effects of aromatase inhibitors were included in the review. SUMMARY OF THE FINDINGS: It has become increasingly clear that bone age advancement depends on the production of estrogen and its effect on the growth plate. In boys, testosterone is converted to estradiol by the cytochrome P450 enzyme aromatase. The use of aromatase inhibitors has been shown to be effective in prolonging the length of the growth phase in children with idiopathic short stature, constitutional growth delay, delayed puberty, as well as in children with growth hormone deficiency, in which bone age advancement jeopardizes the results of hormonal replacement therapy with growth hormones. As yet, significant adverse effects have not been reported, and results are encouraging in terms of effective increase in height, whenever the indication for the drug is appropriate. CONCLUSIONS: Among the pharmacological treatments for short stature, aromatase inhibitors are indicated in cases in which bone age advancement may constitute an obstacle for reaching a final height that is in keeping with the family's target height.

[Brain sex: just beginning to pave the way]. / Sexo cerebral: um caminho que começa a ser percorrido.

It has become clear that a sexual brain dimorphism exists between males and females and animal studies have shown specific circuits developing depending on the sex. Since the first studies by Gorski, in rats, characterizing a sexually dimorphic nucleus in the pre optic area (SDN-POA) it has been accepted that the male sex imprint is done by estradiol, locally converted from testosterone through the action of a local aromatase. The presence of estradiol inhibits the apoptosis of the cells of SDN, making it bigger in the male sex. Other CNS regions have shown sexual dimorphism and we need a marker to allow us to identify these structures and, eventually, apply this information to clinical practice. In intersex patients, it may be of value to know which the brain sex of the patient is, since we have had many doubts in choosing the sex of rearing in many of these patients. It has not been uncommon that sexual inadequacies have occurred in some patients, causing a lot of discomfort and suffering for the patient himself as well as to his family. The progression of the knowledge in the field of brain sex may bring us another tool to deal with difficult cases of sex assignment in intersex patients.

[True hermaphroditism: experience with 36 patients]. / Hermafroditismo verdadeiro: experiência com 36 casos.

AIM: To show data on true hermaphrodites (TH) followed in two reference centers in the state of São Paulo. PATIENTS: Twenty-six TH patients have been followed from 1975 to 2004 in the Pediatric Endocrinology Unit, São Paulo University Medical School, and the other 10 patients from 1989 to 2004 in the GIEDDS-UNICAMP. METHODS: Clinical and pathological data were retrospectively analyzed, as well as the decision about the sex of rearing. RESULTS: Genital ambiguity was the most frequent complaint (34/36 cases) and the age at the first appointment was 20 mo (median). In 55.6% of the patients the female option was taken. The most frequent karyotype was 46,XX (47.2%), followed by mosaicisms (27.8%). SRY was negative in all 46,XX TH patients and the prevalent gonad was ovotestis (OT-47%), followed by ovary (OV-27%) and testis (TT-24%). The prevalent gonadal associations were OV+TT (30.5%), OT+OT (22.2%) and OT+OV (22.2%). The decision about the sex of rearing did not depend on karyotype, phallus size, and testosterone levels. However, the location of the urethral meatus was taken into account in this decision: 20 (80%) patients out of the 25 with perineal urethra were reared as females while all 11 with "non-perineal" urethra were reared as males. In five 46,XX patients reared as females it was possible to maintain the ovarian portion of the ovotestis. CONCLUSION: TH keeps on defying clinicians and investigators since most patients are 46,XX and SRY-negative, and yet they are able to develop testicular and ovarian tissues. The female sex of rearing seems to be the most adequate, and it is important to try to preserve, in these cases, the ovarian portion of the ovotestis, allowing the patient to have normal puberty and fertility.

[XX male: 3 case reports during childhood]. / Homem XX: relato de três casos na faixa etária pediátrica.

We report on three patients with the clinical condition known as "XX male", which is uncommon in the pediatric age group. Patients have a male phenotype (usually without ambiguous genitalia) and testes; however, the karyotype is 46,XX. The diagnosis is usually made in adult life due to infertility; it may also be done by the pediatrician when there is ambiguous genitalia or gynecomastia. The SRY gene (Sex-determining Region of the Y chromosome) is detected in most cases, thus explaining the origin of testicular development; however, it is absent in 20% of the cases, thus indicating that gonadal determination is a complex process which depends on the interaction of many genes and transcription factors. The finding of only 3 cases in two reference services in a 30-year period indicates the rarity of this disorder among intersex cases.

Cortical Brain Functions ­ The Brodmann Legacy in the 21st Century

In 1909, Korbinian Brodmann described 52 functional brain areas, 43 of them found in the human brain. More than a century later, his devoted functional map was incremented by Glasser et al in 2016, using functional nuclear magnetic resonance imaging techniques to propose the existence of 180 functional areas in each hemisphere, based on their cortical thickness, degree of myelination (cortical myelin content), neuronal interconnection, topographic organization, multitask answers, and assessment in their resting state. This opens a huge possibility, through functional neuroanatomy, to understand a little more about normal brain function and its functional impairment in the presence of a disease.

Disorders of Consciousness: Practical Management in an Emergency Room

Lowering of the level of consciousness is a very common presentation at the emergency room, often without any history that helps finding an etiology. This emergency requires quick empirical measures to reduce neuronal mortality, with additional protection against sequelae. According to the Advanced Cardiac Life Support (ACLS) guidelines, there are current emergency neurological support protocols, such as the Emergency Neurological Life Support (ENLS) created by the Neurocritical Care Society. The present paper shows how to approach unconscious patients, highlighting possible etiologies and proposed treatments.

Non-Invasive Intracranial Pressure Evaluation in an Emergency Room ­ Point-of-Care Ultrasonography

Point-of-care ultrasound ismodifying conducts in emergency care. The variousmedical specialties, in addition to traditional indications in cases of multiple trauma, are using this technique for rapid diagnosis at the bedside without patient mobilization and without radiation. Point-of-care ultrasound in neurocritical patients, through its transorbital window, can estimate the intracranial pressure by a non-invasive method. Through the measurement of the diameter of the optic nerve sheath 3mmposterior to the retina, the intracranial pressure is estimated if the value of the diameter is >5mm, as it has been verified in other studies. The present article describes the most current data on this topic, and it also highlights the need formoremulticentric and randomized trials to determine the correct cut-off points that represent the high sensibility and specificity of the method.

Brain Concussion: New Classifications and Current Physiopathological Knowledge of the Disease

The present review paper aims to update the definition and classification of cerebral concussion, highlighting its pathophysiological mechanisms. The high prevalence of cerebral concussion in emergency rooms around the world makes it necessary to know its proper management to avoid its late sequelae, which traditionally compromise cognitive aspects of behavior. New evidence on potential neuroprotective treatments is being investigated.

Unveiling the Insular Lobe of Reil: Neurophysiological and Anatomical Features

The insular lobe has long been investigated, from its anatomical descriptions to its neurophysiological activity. Located in a central location, the insular lobe participates in several afferent and efferent pathways, forming part of the eloquent and fundamental structures that make up the central core of the brain. The lobe of the insula has participation in language function, such as speech, sensory (e.g., taste), limbic, autonomic (visceral), also forming part of complex associative circuits, including part of the circuits of mirror neurons. Several functional descriptions attributed to the insular lobe have beenmade in patients suffering fromcerebrovascular diseases, as well as in those with epilepsy. Much progress and many descriptions have also been made in patients with tumors. Despite much information already available about the insular lobe, it is likely that much will be discovered in the coming years.

Neurogenic Shock: Clinical Management and Particularities in an Emergency Room

Neurogenic shock has a strong impact in traumatology. It is an important condition, associated with lesions in the neuraxis and can be medullar and/or cerebral. In the last years, its pathophysiology has been better understood, allowing a reduction in the morbimortality with more precise and efficacious interventions taking place in the emergency room. In this review article, the author presents the current aspects of the management of neurogenic shock, highlighting the neuroprotective measures that improve the outcome. Many pharmacologic interventions are still questionable and need more prospective studies to accurately assess their real value. The best moment for neurosurgical intervention is also debatable. Quite clearly, the initial proceedings in the emergency room are fundamental to guarantee the adequate conditions for neuroplasticity and neuronal rehabilitation.

Uso rotineiro do colar cervical no politraumatizado. revisão crítica / Routine cervical collar use in polytrauma patients: a critical review

Conforme o conhecimento médico avança, medidas terapêuticas inquestionáveis na medicina de urgências e emergências passaram a ser reconsideradas. O uso do colar cervical no paciente politraumatizado intuitivamente poderia trazer segurança ao paciente, evitando uma possível piora da sua lesão raquimedular. Evidências atuais, no entanto, provam não somente que muitas vezes este dispositivo não traz benefício como agrava lesões intracranianas. Apresentamos aqui uma pesquisa qualitativa e descritiva por meio de revisão narrativa da literatura, trazendo dados recentes quanto à correta indicação para utilização do colar cervical no politraumatizado, apontando também seus malefícios e erros técnicos em sua utilização.(AU)

With the advance of medical knowledge, emergency and urgency medical procedures, once taken for granted, have been modified. Intuitively, the use of a cervical collar in polytrauma patients could be safe for the patient, avoiding a secondary spinal injury. However, recent evidence prove that sometimes this device not only gives no benefit to the patient but also worsen intracranial injuries. This is a qualitative and descriptive research using a narrative review of the literature, and which brings recent data on the correct indication of the cervical collar in the polytrauma patient, showing the harms and technical errors of its use.(AU)

Aspectos neurofuncionais do cerebelo: o fim de um dogma / Neurofunctional Aspects of Cerebellum: The End of a Dogma

Há séculos o cerebelo é considerado uma estrutura do sistema nervoso central responsável exclusivamente pela coordenação do movimento, fazendo diversas conexões com as áreas motoras e associativas do córtex cerebral. No entanto, nos últimos anos, avanços em neuroimagem funcional têm atribuído ao cerebelo funções cognitivo- afetivas, identificando-as anatômica e funcionalmente. Nesta revisão, os autores trazem as mais recentes informações sobre as funções cerebelares, considerando a síndrome cognitivo-afetiva correlacionada ao cerebelo e pondo fim a mais um dogma das neurociências.

For centuries the cerebellum is considered a structure of the central nervous system solely responsible for coordination of the movement, making several connections with themotor areas and associations areas of the cerebral cortex. However, in recent years, advances in functional neuroimaging has assigned the cerebellum cognitive-affective functions, identifying the anatomy and functionally pathways. In this review, the authors come with the latest information about the cerebellar functions, whereas the syndrome cerebellar cognitive-affective, it correlated, putting an end to more a dogma in neuroscience.

[Metabolic syndrome in children and adolescents: doubts about terminology but not about cardiometabolic risks]. / Síndrome metabólica em crianças e adolescentes: dúvidas na terminologia, mas não nos riscos cardiometabólicos.

Metabolic syndrome (MS) has been a condition involved in considerable controversy, starting with the terminology. Gerald Reaven himself, the author who proposed the term MS, advised against the use of this terminology because the definition implies in at least three metabolic alterations, and it is never clear to which group of alterations we are referring to when we say that a patient has MS. In children, the problem is even more complicated, since there are many different adaptations to the criteria used in adults. On the other hand, independent of the terminology, cardiovascular risks are well-established and it is very clear that even children may present metabolic disturbances which predict future metabolic problems. The role of the pediatric endocrinologist or the general pediatrician is to investigate, especially in overweight/obese children, conditions that if treated early, may prevent future complications that today, unfortunately, are being diagnosed only in adult life. In this review, we discuss problems on the definition, epidemiology, pathophysiology, and complications of MS in children and adolescents.

[Attention deficit disorder and hyperactivity: does the treatment affect the statural growth?]. / Hiperatividade e déficit de atenção: o tratamento prejudica o crescimento estatural?

The current study evaluated the influence of stimulant drugs used for attention deficit and hyperactivity (ADH) on statural growth. The authors conducted a literature review collecting published articles on attention deficit hyperactivity disorder and its relationship with short stature. The source of information was the PubMed database where the following terms were researched: "Growth and Methylphenidate"/"Attention deficit and hyperactivity versus short stature"/"Methylphenidate and growth disorders". ADH are difficult clinical situations that interfere with the patient's well-being and social and school performance. Once the diagnosis is attained stimulant medications such as methylphenidate have a key role in the treatment but there are concerns regarding their interference in growth and weight gain. We reviewed many publications regarding these side effects and there is no consensus on them; however, even when they happen to occur their intensity is not sufficient to preclude the use of the medication. We have to take into consideration the cost/benefit relationship, remembering that improvement in school and social performance are very welcome to the child and family. Careful monitoring of the growth chart can detect worsening of growth and its intensity will determine if the drug shall or shall not be interrupted.

[Hyperglycemic acute crisis in type 1 diabetes mellitus in youth]. / Complicações hiperglicêmicas agudas no diabetes melito tipo 1 do jovem.

Diabetic ketoacidosis (DKA) is the main hyperglycemic complication in type 1 Diabetes Mellitus (DM1). The basic principles in treatment have to be followed carefully. The patient with DKA has a very deep volume depletion. To restore the circulatory capacity is the first step. From this point on, the restoration of the lost fluids is slow, around 1% per hour, aiming at the correction of the metabolic disturbance already on and avoiding great fluctuations in osmolality, which increases the risk of having complications. Attention to the development of cerebral edema, which, once suspected, deserves an urgent treatment plan, trying to avoid neurologic sequelae or even death. Subcutaneous ultra-rapid insulin has been demonstrated to be efficient and easier to use. As the perfusion gets improved and the levels of insulin increase, the lipolysis is blocked, as well as the generation of ketones and so the acidemia tends to be solved. DKA is still a high-mortality condition. And to be in a hurry frequently leads to neurologic sequelae and even to a fatal outcome.

Encefalopatias: etiologia, fisiopatologia e manuseio clínico de algumas das principais formas de apresentação da doença / Encephalopathies: etiology, pathophysiology, and clinical management of some major forms of disease presentation

JUSTIFICATIVA E OBJETIVOS: As encefalopatias compõem um grupo heterogêneo de etiologias, onde a pronta e correta atuação médica direcionada à causa da doença, pode modificar o prognóstico do paciente. O objetivo deste estudo foi rever os aspectos fisiopatológicos das diferentes encefalopatias bem como seus principais fatores desencadeantes e manuseio clínico.CONTEÚDO: Foram selecionadas as mais frequentes encefalopatias observadas na prática clínica e discutir sua fisiopatologia, bem como sua abordagem terapêutica, destacando: encefalopatia hipertensiva, hipóxico-isquêmica, metabólica, Wernicke-Korsakoff, traumática e tóxica.CONCLUSÃO: Trata-se de uma complexa condição clínica que exige rápida identificação e preciso manuseio clínico com o intuito de reduzir sua elevada taxa de morbimortalidade. O atraso no reconhecimento dessa condição clínica poderá ser extremamente prejudicial ao paciente que estará sofrendo lesão cerebral muitas vezes irreversível.

BACKGROUND AND OBJECTIVES: Encephalopathies comprise a heterogeneous group of clinical conditions, in which the prompt and adequate medical intervention can modify patient prognosis. This paper aims to discuss the pathophysiological aspects of different encephalopathies, their etiology, and clinical management.CONTENTS: We selected the main encephalopathies observed in clinical practice, such as hypertensive, hypoxic-ischemic, metabolic, Wernicke-Korsakoff, traumatic, and toxic encephalopathies, and to discuss their therapeutic approaches.CONCLUSION: This is a complex clinical condition that requires rapid identification and accurate clinical management with the aim of reducing its high morbidity and mortality rates. Delay in recognizing this condition can be extremely harmful to the patient who is suffering from often irreversible brain injury.