Inducible CRISPR Epigenome Systems Mimic Cocaine Induced Bidirectional Regulation of Nab2 and Egr3.

Substance use disorder is a chronic disease and a leading cause of disability around the world. The NAc is a major brain hub mediating reward behavior. Studies demonstrate exposure to cocaine is associated with molecular and functional imbalance in NAc medium spiny neuron subtypes (MSNs), dopamine receptor 1 and 2 enriched D1-MSNs and D2-MSNs. We previously reported repeated cocaine exposure induced transcription factor early growth response 3 (Egr3) mRNA in NAc D1-MSNs, and reduced it in D2-MSNs. Here, we report our findings of repeated cocaine exposure in male mice inducing MSN subtype-specific bidirectional expression of the Egr3 corepressor NGFI-A-binding protein 2 (Nab2). Using CRISPR activation and interference (CRISPRa and CRISPRi) tools combined with Nab2 or Egr3-targeted sgRNAs, we mimicked these bidirectional changes in Neuro2a cells. Furthermore, we investigated D1-MSN- and D2-MSN-specific expressional changes of histone lysine demethylases Kdm1a, Kdm6a, and Kdm5c in NAc after repeated cocaine exposure in male mice. Since Kdm1a showed bidirectional expression patterns in D1-MSNs and D2-MSNs, like Egr3, we developed a light-inducible Opto-CRISPR-KDM1a system. We were able to downregulate Egr3 and Nab2 transcripts in Neuro2A cells and cause similar bidirectional expression changes we observed in D1-MSNs and D2-MSNs of mouse repeated cocaine exposure model. Contrastingly, our Opto-CRISPR-p300 activation system induced the Egr3 and Nab2 transcripts and caused opposite bidirectional transcription regulations. Our study sheds light on the expression patterns of Nab2 and Egr3 in specific NAc MSNs in cocaine action and uses CRISPR tools to further mimic these expression patterns.SIGNIFICANCE STATEMENT Substance use disorder is a major societal issue. The lack of medication to treat cocaine addiction desperately calls for a treatment development based on precise understanding of molecular mechanisms underlying cocaine addiction. In this study, we show that Egr3 and Nab2 are bidirectionally regulated in mouse NAc D1-MSNs and D2-MSNs after repeated exposure to cocaine. Furthermore, histone lysine demethylations enzymes with putative EGR3 binding sites showed bidirectional regulation in D1- and D2-MSNs after repeated exposure to cocaine. Using Cre- and light-inducible CRISPR tools, we show that we can mimic this bidirectional regulation of Egr3 and Nab2 in Neuro2a cells.

Maintenance single-agent bevacizumab or observation after first-line chemotherapy in patients with metastatic colorectal cancer: a multicenter retrospective study.

The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: "maintenance bevacizumab cohort (n = 118; MB)", and those discontinuing bevacizumab as a result of physician's or patient's decision: "no maintenance bevacizumab cohort (n = 102; noMB)". The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7-15) and 22.5 months (range 18-26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.

Adaptations in Nucleus Accumbens Neuron Subtypes Mediate Negative Affective Behaviors in Fentanyl Abstinence.

BACKGROUND: Opioid discontinuation generates a withdrawal syndrome marked by increased negative affect. Increased symptoms of anxiety and dysphoria during opioid discontinuation are significant barriers to achieving long-term abstinence in opioid-dependent individuals. While adaptations in the nucleus accumbens are implicated in opioid abstinence syndrome, the precise neural mechanisms are poorly understood. Additionally, our current knowledge is limited to changes following natural and semisynthetic opioids, despite recent increases in synthetic opioid use and overdose. METHODS: We used a combination of cell subtype-specific viral labeling and electrophysiology in male and female mice to investigate structural and functional plasticity in nucleus accumbens medium spiny neuron (MSN) subtypes after fentanyl abstinence. We characterized molecular adaptations after fentanyl abstinence with subtype-specific RNA sequencing and weighted gene co-expression network analysis. We used viral-mediated gene transfer to manipulate the molecular signature of fentanyl abstinence in D1-MSNs. RESULTS: Here, we show that fentanyl abstinence increases anxiety-like behavior, decreases social interaction, and engenders MSN subtype-specific plasticity in both sexes. D1-MSNs, but not D2-MSNs, exhibit dendritic atrophy and an increase in excitatory drive. We identified a cluster of coexpressed dendritic morphology genes downregulated selectively in D1-MSNs that are transcriptionally coregulated by E2F1. E2f1 expression in D1-MSNs protects against loss of dendritic complexity, altered physiology, and negative affect-like behaviors caused by fentanyl abstinence. CONCLUSIONS: Our findings indicate that fentanyl abstinence causes unique structural, functional, and molecular changes in nucleus accumbens D1-MSNs that can be targeted to alleviate negative affective symptoms during abstinence.

Corticostriatal contributions to dysregulated motivated behaviors in stress, depression, and substance use disorders.

Coordinated network activity, particularly in circuits arising from the prefrontal cortex innervating the ventral striatum, is crucial for normal processing of reward-related information which is perturbed in several psychiatric disorders characterized by dysregulated reward-related behaviors. Stress-induced depression and substance use disorders (SUDs) both share this common underlying pathology, manifested as deficits in perceived reward in depression, and increased attribution of positive valence to drug-predictive stimuli and dysfunctional cognition in SUDs. Here we review preclinical and clinical data that support dysregulation of motivated and reward-related behaviors as a core phenotype shared between these two disorders. We posit that altered processing of reward-related stimuli arises from dysregulated control of subcortical circuits by upstream regions implicated in executive control. Although multiple circuits are directly involved in reward processing, here we focus specifically on the role of corticostriatal circuit dysregulation. Moreover, we highlight the growing body of evidence indicating that such abnormalities may be due to heightened neuroimmune signaling by microglia, and that targeting the neuroimmune system may be a viable approach to treating this shared symptom.

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice.

Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however, most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 days fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl over time. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.

The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes.

Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.

Unlocking mammalian regeneration through hypoxia inducible factor one alpha signaling.

Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Recently, investigations into tadpole tail regrowth, zebrafish limb restoration, and the super-healing Murphy Roths Large (MRL) mouse strain, have identified ancient oxygen-sensing pathways as a possible target to achieve this goal. Specifically, upregulation of the transcription factor, hypoxia-inducible factor one alpha (HIF-1α) has been shown to modulate cell metabolism and plasticity, as well as inflammation and tissue remodeling, possibly priming injuries for regeneration. Since HIF-1α signaling is conserved across species, environmental or pharmacological manipulation of oxygen-dependent pathways may elicit a regenerative response in non-healing mammals. In this review, we will explore the emerging role of HIF-1α in mammalian healing and regeneration, as well as attempts to modulate protein stability through hyperbaric oxygen treatment, intermittent hypoxia therapy, and pharmacological targeting. We believe that these therapies could breathe new life into the field of regenerative medicine.

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

[Two cases of Werdnig-Hofmann disease]. / Enfermedad de Werdnig-Hofmann. Dos casos clínicos.

Spinal muscular atrophy (SMA) is an autonomic recessive disorder that affects the anterior horn cells of the spinal cord, degeneration of which results in proximal muscle weakness. It is classified into three types: I and II (Werdnig-Hoffmann disease) and III (Kugelberg-Welander disease). With an incidence of 1/10,000. We report two cases of infants with hypotonic syndrome, that were diagnose with SMA, in the first case by muscular biopsy, and in the second by electromyography and chromosomes study. It is import that the physicians know about this disease, and its complications.

Early-life ketamine exposure attenuates the preference for ethanol in adolescent Sprague-Dawley rats.

Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces quick and effective antidepressant results in depressed juvenile and adult individuals. The long-term consequences of using ketamine in juvenile populations are not well known, particularly as it affects vulnerability to drugs of abuse later in life, given that ketamine is also a drug of abuse. Thus, the current study examined whether early-life ketamine administration produces long-term changes in the sensitivity to the rewarding effects of ethanol, as measured using the conditioned place preference (CPP) paradigm. On postnatal day (PD) 21, juvenile male and female rats were pretreated with ketamine (0.0 or 20 mg/kg) for 10 consecutive days (i.e., PD 21-30) and then evaluated for ethanol-induced CPP (0.0, 0.125, 0.5, or 2.0 g/kg) from PD 32-39. Results revealed that early-life ketamine administration attenuated the rewarding properties of ethanol in male rats, as ketamine pretreated rats failed to exhibit ethanol-induced CPP at any dose compared to saline pretreated rats, which showed an increased preference towards the ethanol-paired compartment in a dose-dependent manner. In females, ethanol-induced CPP was generally less robust compared to males, but ketamine pretreatment resulted in a rightward shift in the dose-response curve, given that ketamine pretreated rats needed a higher dose of ethanol compared to saline pretreated rats to exhibit ethanol-induced CPP. When considered together, the findings suggest that early use of ketamine does not appear to enhance the vulnerability to ethanol later in life, but in contrast, it may attenuate the rewarding effects of ethanol.

Percepción bioética de ginecólogos residentes de mastología sobre la interrupción del embarazo en cáncer de seno / Bioethical perception of gynecology specialist mastology residents regarding pregnancy interruption in cases with breast cancer

Objetivo: describir la percepción bioética en un grupo de residentes de mastología frente a la interrupción voluntaria en el primer trimestre del embarazo (IVE,) en casos con cáncer de mama temprano, y las implicaciones de sus conductas médicas en un hospital universitario. Metodología: estudio cualitativo de tipo fenomenológico descriptivo. La técnica de recolección de datos fue la entrevista a profundidad, Para la inclusión de los participantes se utilizó un muestreo intencional. La información se analizó siguiendo el método de Colaizzi que considera la codificación abierta, axial y selectiva. Se elaboraron matrices (microsoft office Excel) para el análisis y comparación de los datos, y para las categorías mediante la consolidación de los descriptores. Para mantener el rigor de la investigación y la validez de sus resultados se tuvieron en cuenta los criterios de credibilidad, auditabilidad y transferibilidad propuestos por Lincoln y Guba, analizando los datos dos investigadores para triangulación de la información. Estudio de riesgo mínimo dado que no se modifican variables en los participantes, se tuvieron en cuenta consideraciones de la Resolución 8430 de 1993 y se obtuvo aprobación del comité de ética de investigación en seres humanos. Resultados: participaron médicos, especialistas en ginecología y obstetricia, residentes de la especialidad de mastología. A partir de la categorización de los significados formulados de las entrevistas, se organizaron en cinco categorías que dan cuenta del dilema de sugerir o no la interrupción de un embarazo en mujeres con cáncer de mama temprano, dudas de los profesionales encargados en la toma de decisiones y sensación de carga de responsabilidad aumentada. Conclusión: la autonomía del médico se ve afectada en casos complejos, en especial cuando considera que no es adecuada la interrupción. Se debería incluir en los programas académicos una formación en bioética no principialista sino centrada en la persona.

Objective: to describe the bioethical perception of a group of mastology residents regarding first trimester voluntary pregnancy interruption (VPI) in cases with early-stage breast cancer, and the implications of their medical behaviors in a university hospital. Methodology: a qualitative descriptive phenomenological study was conducted. Data was obtained through in-depth interviews. Purposive sampling was adopted for recruiting participants. Colaizzi ́s method was used for data analysis including open, axial, and selective coding. Analysis and comparison matrices, and for categories by descriptors consolidation, were created in Microsoft Office Excel. The credibility, auditability, and transferability criteria proposed by Lincoln and Guba, were used to ensure research rigor and validity of its results. Data triangulation was performed involving two researchers. This is a minimal risk study given no variables are modified in participants, in accordance with Resolution 8430 of 1993. Approval was obtained from the ethics committee for research on human beings. Results: participants included physicians, gynecology, and obstetrics specialists, and mastology residents. They were categorized into five groups based on the categorization of the meanings proposed in the interviews, that account for the dilemma of whether suggesting pregnancy interruption in women with early-stage breast cancer, concerns of physicians who play the decision-making role and a feeling of increased responsibility burden placed on them. Conclusion: physician ́s autonomy is affected in complex cases, especially when he/she considers that pregnancy interruption is not appropriate. Training in bioethics should be provided in academic programs, not based on principles but as a person-centered approach.

Linfoma de células T/natural killer extranodal de tipo nasal enmascarado en una sinusopatia

Introducción: El linfoma de células T citotóxico/natural killer extranodal de tipo nasal es poco frecuente, pero con alta tasa de mortalidad. Las manifestaciones clínicas de la enfermedad pueden simular una infección de senos paranasales. Objetivo: Presentar las manifestaciones clínicas de un paciente de 34 años de edad con diagnóstico de linfoma de células T citotóxico/natural killer extranodal de tipo nasal. Caso clínico: Se presenta un paciente masculino de 34 años de edad con rinorrea verdosa fétida recurrente y obstrucción en fosa nasal derecha. En la evaluación inicial sugiere sinusitis crónica, sin embargo, debido al empeoramiento de las manifestaciones clínicas se realiza una tomografía computarizada que muestra lesiones sugestivas de infiltración neoplásica, una biopsia de la lesión confirma el diagnóstico de linfoma de células T/natural killer extranodal de tipo nasal. Conclusiones: Los linfomas de células T citotóxico/natural killer extranodal de tipo nasal son considerados neoplasias poco frecuentes, caracterizadas por el patrón rápidamente progresivo con afectación ósea; en su etapa inicial presenta manifestaciones clínicas similares a una sinusitis. La tomografía computarizada y la histopatología, son indispensables en el diagnóstico de la enfermedad.

Introduction: Nasal-type extranodal natural killer/cytotoxic T-cell lymphoma is rare but has a high mortality rate. The clinical manifestations of the disease can mimic a paranasal sinus infection. Objective: To present the clinical manifestations of a 34-year-old patient diagnosed with nasal-type extranodal natural killer/cytotoxic T-cell lymphoma. Clinical case: A 34-year-old male patient with recurrent greenish fetid rhinorrhea and obstruction in the right nostril is presented. In the initial evaluation, it suggests chronic sinusitis, however, due to the worsening of the clinical manifestations, a computed tomography is performed that shows lesions suggestive of neoplastic infiltration, a biopsy of the lesion confirms the diagnosis of T-cell lymphoma/extranodal natural killer. Conclusions: Nasal-type extranodal natural killer/cytotoxic T-cell lymphomas are considered rare neoplasms characterized by a rapidly progressive pattern with bone involvement; in its initial stage it presents clinical manifestations similar to sinusitis. Computed tomography and histopathology are essential in the diagnosis of the disease.

Toxic Epidermal Necrolysis and Sepsis.

A 63-year-old male patient suffered from myalgia, arthralgia cough and erythematous macules, with confluence to the thorax, limbs, thighs and the scrotum. The erythematous macules evolved to blisters with a positive Nikolsky's sign. A cutaneous biopsy revealed satellite cell necrosis. Administration of immunoglobulins resulted in a favourable evolution of the cutaneous lesions. Toxic epidermal necrolysis (TEN) is a rare and potentially fatal mucocutaneous disease. Early recognition, diagnosis and therapy are of the utmost importance. LEARNING POINTS: Toxic epidermal necrolysis (TEN) is a rare and potentially fatal mucocutaneous disease.TEN requires early diagnosis, appropriate workup and treatment to minimise potential morbidity and mortality.Today immunoglobulin therapy is the most accepted form of treatment for TEN.

Perforated duodenal ulcer after laparoscopic roux-y gastric bypass. Case report / Perforación duodenal posterior a bypass gástrico con reconstrucción en Y de Roux. Reporte de caso

SUMMARY Introduction: Gastric bypass is one of the strategies that have shown better results in the management of obesity, since this technique is the one that strikes a better balance between risk, side effects and long-term results. It consists in the creation of a gastric reservoir that anastomosis to the jejunum, reducing the size of the gastric chamber and thus the patient tolerates less food and decreasing its intake. One of the less frequent late complications is duodenal perforation. For this reason, we present this case report, according to the CARE guideline. Case presentation: 47-year-old male patient with a history of gastric bypass due to obesity, who consults for sudden onset of abdominal pain. Physical examination showed signs of peritoneal irritation and systemic inflammatory response. Exploratory laparoscopy was performed with suspected hollow viscus perforation, which evidenced a 1 cm ulcer on the anterior aspect of the duodenal bulb, requiring omentoplasty by laparotomy. Conclusions: Perforated duodenal ulcer in patients with a history of gastric bypass is a rare diagnosis. It has a non-specific clinical presentation, which is why exploratory laparoscopy is considered a valid diagnostic and therapeutic strategy.

RESUMEN Introducción: una de las estrategias que han demostrado resultados superiores para el manejo de la obesidad es el bypass gástrico, ya que esta técnica es la que reúne un major equilibrio entre el riesgo, efectos secundarios y los resultados a largo plazo. Consiste en la creación de un reservorio gástrico que se anastomosa al yeyuno, reduciendo el tamaño de la cámara gástrica y haciendo que el paciente tolere menos los alimentos, para que se disminuya la ingesta de estos. Dentro de las complicaciones tardías menos frecuentes se encuentra la perforación duodenal, motivo por el cual se presenta este reporte de caso de acuerdo con la guía CARE. Presentación del caso: hombre de 47 años y antecedente de bypass gástrico por obesidad, que consulta por dolor abdominal de inicio súbito. A la valoración con examen físico con hallazgos de irritación peritoneal y signos de respuesta inflamatoria sistémica. Es llevado a laparoscopia exploratoria con sospecha de perforación de la víscera hueca. Se evidenció una úlcera en la cara anterior del bulbo duodenal de 1 cm que requirió de epiploplastia por laparotomía. Conclusiones: la úlcera duodenal perforada en pacientes con antecedente de bypass gástrico es un diagnóstico poco frecuente con presentación clínica inespecífica, por esto se considera la laparoscopia exploratoria como una estrategia diagnóstica y terapéutica válida.

[Spontaneous Non Ischaemic Blue Finger: A Rare and Benign Phenomenon]. / Dedo Azul Não-Isquémico Espontâneo: Um Fenómeno Raro e Benigno.

The spontaneous non-ischaemic blue finger is a rare and benign disorder, characterized by purple discoloration of a finger, with complete resolution. This article reports the case of a woman of 88 years, which after a few hours of stay in the emergency department developed without associated trauma, a purplish color of the 3rd finger of the right hand, with a palpable pulse and without temperature changes or pain. The etiological investigation was negative. The patient was assessed one week after the event and showed completeresolution. There are several diseases that share the same signs and symptoms, as such the diagnosis is based on the spontaneous violaceous color sparing the finger tip, and fast resolution without treatment. Though being a harmless phenomenon, it requires early assessment for timely differential diagnosis with severe pathologies.

O dedo azul não-isquémico espontâneo é uma entidade rara e benigna, caracterizada pela alteração da coloração isolada de um dedo, com aparecimento e resolução espontânea. Este artigo relata o caso de uma mulher de 88 anos, que após algumas horas de permanência no serviço de urgência desenvolveu, sem trauma associado uma coloração violácea do terceiro dedo da mão direita, com pulsos mantidos, sem alteração da temperatura e indolor. A pesquisa etiológica realizada foi negativa. A doente foi reavaliada uma semana após o evento e mostrava regressão total da lesão. Apesar de existirem várias patologias que partilham sinais e sintomassemelhantes, o diagnóstico baseia-se no aparecimento espontâneo, na coloração violácea característica que poupa a polpa do dedo, e na resolução rápida sem necessidade de tratamento. Mesmo sendo um fenómeno benigno necessita de avaliação precoce para que o diagnóstico diferencial com patologias mais graves seja feito atempadamente.

Achados fonoaudiológicos de crianças com queixa de distúrbio de fala / Speech and language assessment from children's complaint associated with speech disorder

Este trabalho teve como objetivo investigar os achados fonoaudiológicos em crianças de 04 a 06 anos com queixa de distúrbios de fala, por meio da análise de frequencia de ocorrência e análise comparativa destas possíveis alteraçöes, referidas em 30 prontários de avaliaçäo fonoaudiológica do Ambulatório dos Distúrbios da Comunicaçäo Humana da Universidade Federal de Säo Paulo-Escola Paulista de Medicina. A escolha dos aspectos considerados neste estudo foi baseada na frequencia de aparecimento de informaçöes no total dos prontuários. Foi constatado que 100 por cento dos prontuários realmente apresentaram algum tipo de distúrbio de fala além de outras alteraçöes fonoaudiológicas. No entanto, as queixas, inicialmente apresentadas pelos pais, näo revelaram outras preocupaçöes. Em relaçäo à fala, as alteraçöes mais observadas ocorreram no quadro fonêmico, sendo que houve concordância entre a presença de troca e omissäo em relaçäo à distribuiçäo, o que foi estatisticamente significante. Quanto às demais alteraçöes fonoaudiológicas, as mais frequentes foram: de linguagem, do aparelho estomatognático, das funçöes estomatognáticas e disfonia.