High fat diet-induced obesity causes a reduction in brain tyrosine hydroxylase levels and non-motor features in rats through metabolic dysfunction, neuroinflammation and oxidative stress.

Obesity is a health problem that has been associated with neuroinflammation, decreased cognitive functions and development of neurodegenerative diseases. Parkinson's disease (PD) is a chronic neurodegenerative condition characterized by motor and non-motor abnormalities, increased brain inflammation, α-synuclein protein aggregation and dopaminergic neuron loss that is associated with decreased levels of tyrosine hydroxylase (TH) in the brain. Diet-induced obesity is a global epidemic and its role as a risk factor for PD is not clear. Herein, we showed that 25 weeks on a high-fat diet (HFD) promotes significant alterations in the nigrostriatal axis of Wistar rats. Obesity induced by HFD exposure caused a reduction in TH levels and increased TH phosphorylation at serine 40 in the ventral tegmental area. These effects were associated with insulin resistance, increased tumor necrosis factor-α levels, oxidative stress, astrogliosis and microglia activation. No difference was detected in the levels of α-synuclein. Obesity also induced impairment of locomotor activity, total mobility and anxiety-related behaviors that were identified in the open-field and light/dark tasks. There were no changes in motor coordination or memory. Together, these data suggest that the reduction of TH levels in the nigrostriatal axis occurs through an α-synuclein-independent pathway and can be attributed to brain inflammation, oxidative/nitrosative stress and metabolic disorders induced by obesity.

Handling suicidal crises in psychodynamic psychotherapy: A process case study.

The core characteristics of patients with a borderline personality disorder (BPD) affect the therapeutic relationship and frequently lead psychodynamic therapists to adapt interventions to manage crises. This study aims to increase knowledge of how such crises affect the therapeutic process. Using her therapist's notes, combined with the Psychotherapy Process Q-Set, we studied the therapeutic process of the first 44 therapy sessions of a female BPD patient with many depressive-like symptoms, including a disruptive period that included hospitalization. We found marked differences between different phases of therapy (before a crisis, acute disorganization, hospitalization, and back to the consulting room). The analysis suggests that a crisis and hospitalization may occur without necessarily damaging the therapeutic process. The therapist's ability to tolerate aggression, to explore and contain suicide wishes and behaviors, and to flexibly adapt techniques to patient needs, are among the therapeutic attitudes and behaviors that can help restore an effective psychodynamic process.

Decompression of the tympanic and labyrinthine segments of the facial nerve by middle cranial fossa approach: an anatomic study.

BACKGROUND: Peripheral facial palsy is characterized by the permanent or temporary interruption of facial muscle function. The middle cranial fossa (MCF) approach has been used to decompress the facial nerve (FN) when hearing needs to be preserved. In this work, we describe a technique for decompressing the FN through the MCF approach, which allows the direct exposure of the labyrinthine and entire tympanic segment of the FN, with preservation of inner ear function. METHODS: Twenty cadavers heads were used in this study. The reference landmarks used were the middle meningeal artery, greater superficial petrosal nerve, arcuate eminence, inferior petrosal sinus and meatal plane following the petrous apex from its most anterior and medial portion. RESULTS: The tympanic segment of the FN presented, on average, a total length of 11 ± 0.67 mm to the right and 11.5 ± 0.60 mm to the left. The longitudinal lengths of the bone window in the tegmen tympani were 16.8 ± 1.67 mm to the right and 16.8 ± 1.20 mm to the left. The cross-sectional lengths of the bone window in the tegmen tympani were 5.5 ± 1.20 mm and 5.0 ± 1.75 mm to the right and left sides, respectively. The average value of the elliptical area formed by the longitudinal and transversal lengths of the bone window made in the tegmen tympani was 72.5 ± 22.5 mm(2) to the right and 65.9 ± 30.3 mm(2) to the left. CONCLUSION: The proposed technique can be used for the surgical decompression of the tympanic, labyrinthine and meatal segments of the FN through the MCF in addition to reducing the surgical time and the risk to patients.

The chaperone balance hypothesis: the importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management.

Recent evidence shows divergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For example, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways. Increased eHSP70 is associated with inflammatory and oxidative stress conditions, whereas decreased iHSP70 levels are related to insulin resistance in skeletal muscle. Serum eHSP70 concentrations are positively correlated with markers of inflammation, such as C-reactive protein, monocyte count, and TNF-α, while strategies to enhance iHSP70 (e.g., heat treatment, chemical HSP70 inducers or coinducers, and physical exercise) are capable of reducing the inflammatory profile and the insulin resistance state. Here, we present recent findings suggesting that imbalances in the HSP70 status, described by the [eHSP70]/[iHSP70] ratio, may be determinant to trigger a chronic proinflammatory state that leads to insulin resistance and T2DM development. This led us to hypothesize that changes in this ratio value could be used as a biomarker for the management of the inflammatory response in insulin resistance and diabetes.

Programming peculiarities in two cochlear implant users with superficial siderosis of the central nervous system.

OBJECTIVE: To report the audiological outcomes of cochlear implantation in two patients with severe to profound sensorineural hearing loss secondary to superficial siderosis of the CNS and discuss some programming peculiarities that were found in these cases. METHOD: Retrospective review. Data concerning clinical presentation, diagnosis and audiological assessment pre- and post-implantation were collected of two patients with superficial siderosis of the CNS. RESULTS: Both patients showed good hearing thresholds but variable speech perception outcomes. One patient did not achieve open-set speech recognition, but the other achieved 70% speech recognition in quiet. Electrical compound action potentials could not be elicited in either patient. Map parameters showed the need for increased charge. Electrode impedances showed high longitudinal variability. CONCLUSION: The implants were fairly beneficial in restoring hearing and improving communication abilities although many reprogramming sessions have been required. The hurdle in programming was the need of frequent adjustments due to the physiologic variations in electrical discharges and neural conduction, besides the changes in the impedances. Patients diagnosed with superficial siderosis may achieve limited results in speech perception scores due to both cochlear and retrocochlear reasons. Careful counseling about the results must be given to the patients and their families before the cochlear implantation indication.

Heat shock response to exercise in pancreatic islets of obese mice.

Chronic obesity imposes an organismal state of low-grade inflammation because the physiological resolution of inflammation is progressively repressed giving rise to cellular senescence and its accompanying Senescence-Associated Secretory Phenotype (SASP), which avoids apoptosis but perpetuates the relay of inflammatory signals from adipose tissue toward the rest of the body. Conversely, resolution of inflammation depends on the integrity of heat shock response (HSR) pathway that leads to the expression of cytoprotective and anti-inflammatory protein chaperones of the 70 kDa family (HSP70). However, chronic exposure to the aforementioned injuring factors leads to SASP, which, in turn, suppresses the HSR. A main metabolic tissue severely jeopardized by obesity-related dysfunctions is the endocrine pancreas, particularly ß-cells of the islets of Langerhans. Because exercise is a powerful inducer of HSR and predicted to alleviate negative health outcomes of obesity, we sought whether obesity influence HSP70 expression in pancreatic islets and other metabolic tissues (adipose tissue and skeletal muscle) of adult B6.129SF2/J mice fed on a high-fat diet (HFD) for 13 weeks since the weaning and whether acute exercise as well as moderate-intensity exercise training (8 weeks) could interfere with this scenario. We showed that acute exercise of moderate intensity protects pancreatic islets against cytokine-induced cell death. In addition, acute exercise challenge time-dependently increased islet HSP70 that peaked at 12 h post-exercise in both trained and untrained mice fed on a control diet, suggesting an adequate HSR to exercise training. Unexpectedly, however, neither exercise training nor acute exercise challenges were able to increase islet HSP70 contents in trained mice submitted to HFD, but only in untrained HFD animals. In parallel, HFD disrupted glycemic status which is accompanied by loss of muscular mass resembling sarcopenic obesity that could not be rescued by exercise training. These results suggest that exercise influences HSR in pancreatic islets but obesity undermines islet, muscle and adipose tissue HSR, which is associated with metabolic abnormalities observed in such tissues.

Efeitos da terapia renal substitutiva no sistema auditivo: uma revisão de escopo / Effects of renal replacement therapy on the auditory system: a scoping review / Efectos del tratamiento renal sustitutivo sobre el sistema auditivo: una revisión general

Objetivo: responder as seguintes questões: A) Quais os efeitos no sistema auditivo da terapia renal substitutiva em pacientes dialíticos? B) Quais os principais métodos utilizados para avaliar o sistema auditivo de pacientes dialíticos? Método: Revisão de escopo realizada no mês de janeiro de 2023, utilizando as bases PubMed, Scielo e Medline. Foram utilizados descritores a partir dos seguintes eixos temáticos: terapia renal substitutiva e alterações no sistema auditivo. Resultados: Foram encontrados 358 artigos. Após critérios de elegibilidade, 15 foram incluídos neste estudo. A maioria dos estudos (66,6%) apresentou alteração auditiva para indivíduos que estavam em terapia renal substitutiva, destes (20,0%) descreveram alteração coclear. A perda do tipo neurossensorial nas altas frequências foi a mais frequente com respostas ausentes para as emissões otoacústicas. Foram identificados oito diferentes métodos para avaliação auditiva desta população, sendo o mais utilizado para acompanhamento auditivo a audiometria tonal (73,3%) e a imitânciometria (33,3%). O teste de emissões otoacústicas é o mais citado para diagnóstico precoce. Conclusão: Pacientes em TRS apresentam perda auditiva do tipo neurossensorial nas frequências altas, com grau variando de acordo com o número de terapia renal duração da insuficiência renal. Curvas timpanométricas do tipo A e ausência de respostas nas EOA. O teste mais utilizado para acompanhamento auditivo desta população é a Audiometria Tonal, porém as EOA são os testes mais citados para diagnóstico precoce.

Aim: to answer the following questions: A) What are the effects on the auditory system of renal replacement therapy in dialysis patients? B) What are the main methods used to evaluate the auditory system in dialysis patients? Method: Scoping review conducted in January 2023 using PubMed, Scielo and Medline. Descriptors were used from the following thematic axes: renal replacement therapy and auditory system changes. Results: 358 articles were found. After eligibility criteria, 15 were included in this study. Most studies (66.6%) presented hearing loss in individuals who were on renal replacement therapy, and of these (20.0%) described cochlear alteration. The sensorineural type loss in the high frequencies was the most frequent with absent responses for otoacoustic emissions. Eight different methods were identified for hearing assessment in this population, with tonal audiometry (73.3%) and immittance audiometry (33.3%) being the most used for hearing monitoring. The otoacoustic emissions test is the most cited for early diagnosis. Conclusion: Patients on SRT have sensorineural hearing loss in the high frequencies, with the degree varying according to the number of renal therapy duration of renal failure. Type A tympanometric curves and absence of OAE responses. The most commonly used test for auditory monitoring in this population is Tonal Audiometry, but OAE is the most cited test for early diagnosis.

Objetivo: responder a las siguientes preguntas: A) ¿Cuáles son los efectos sobre el sistema auditivo del tratamiento renal sustitutivo en pacientes en diálisis? B) ¿Cuáles son los principales métodos utilizados para evaluar el sistema auditivo en pacientes en diálisis? Método: Revisión exploratoria realizada en enero de 2023, utilizando las bases de datos PubMed, Scielo y Medline. Se utilizaron descriptores de los siguientes ejes temáticos: terapia renal sustitutiva y alteraciones del sistema auditivo. Resultados: Se encontraron 358 artículos. Tras los criterios de elegibilidad, se incluyeron 15 en este estudio. La mayoría de los estudios (66,6%) presentaban hipoacusia en individuos en tratamiento renal sustitutivo, de éstos (20,0%) describían alteración coclear. La hipoacusia neurosensorial en altas frecuencias fue el tipo más frecuente, con ausencia de respuestas para las otoemisiones acústicas. Se identificaron ocho métodos diferentes para la evaluación auditiva en esta población, siendo la audiometría tonal (73,3%) y la audiometría de inmitancia (33,3%) los más utilizados para el control auditivo. La prueba de otoemisiones acústicas es la más citada para el diagnóstico precoz. Conclusión: Los pacientes en TRS presentan hipoacusia neurosensorial en las frecuencias agudas, variando el grado según el número de tratamientos renales y la duración de la insuficiencia renal. Curvas timpanométricas de tipo A y ausencia de respuestas OAE. La audiometría tonal es la prueba más utilizada para el control auditivo en esta población, pero la OAE es la prueba más mencionada para el diagnóstico precoz.

Estruturas de interação no tratamento psicodinâmico de uma paciente com Transtorno de Personalidade Borderline / Estructuras de interacción en el tratamiento psicodinámico de un paciente con Trastorno Límite de la Personalidad / Interaction Structures in the Psychodynamic Therapy of a Patient with Borderline Personality Disorder

Estruturas de interação são padrões repetitivos que ocorrem entre terapeuta e paciente, mesmo que am-bos não sejam conscientes disso. Na pesquisa empíri-ca, elas ajudam a compreender como se estabelece o processo de mudança em psicoterapia. Nesse sentido, esta investigação utilizou 68 sessões de psicoterapia psicanalítica de um caso de uma jovem paciente com Transtorno de Personalidade Borderline (tpb) com o objetivo de identificar as estruturas de interação e sua correlação com o tempo de tratamento. Os dados fo-ram gravados em vídeo e posteriormente codificados através do Psychotherapy Process Q-Set (pqs), por duplas de juízes treinados na metodologia Q-Sort. A partir desses dados, foi realizada a análise fatorial do tipo Q de componentes principais que indicou quatro estruturas de interação, sendo fator 1: Colaborativo; fa-tor 2: Resistência; fator 3: Aliança/Ruptura e fator 4: Apoio/Encorajamento. As estruturas indicaram que a interação se voltou para o trabalho de manutenção da interação colaborativa, através de uma posição empá-tica do terapeuta, direcionado para o reconhecimento dos estados internos do paciente. Apesar do trabalho colaborativo, a resistência também surgiu como um padrão repetitivo. O terapeuta se tornou diretivo com intervenções estruturadas e questionando o paciente, desta forma contribuindo para o desenvolvimento da capacidade de mentalização. Implicações sobre o pro-cesso psicoterápico e indicações para estudos futuros são apresentados com o intuito de contribuir na com-preensão sobre o tratamento de pacientes com tpb em psicoterapia psicodinâmica.

Las estructuras de interacción son patrones repetitivos que ocurren entre el terapeuta y el paciente, incluso si ambos no son conscientes de esto. En la investigación empírica ayudan a comprender cómo se establece el proceso de cambio en psicoterapia. En tal sentido, esta investigación utilizó 68 sesiones de psicoterapia psicoanalítica del caso de un paciente joven con Tras-torno Límite de la Personalidad (tlp) para identificar las estructuras de interacción y su correlación con el momento del tratamiento. Los datos fueron grabados en video y posteriormente codificados utilizando el Q-Set Proceso de Psicoterapia (pqs), por pares de jueces en-trenados en la metodología Q-Sort. Con base en estos datos, se realizó un análisis factorial del tipo Q de componentes principales, el cual indicó cuatro estructuras de interacción, siendo factor 1: Colaborativo; factor 2: Resistencia; factor 3: Alianza/Disrupción y factor 4: Apoyo/Estímulo. Las estructuras indicaron que la interacción se tornó al trabajo de mantener la interacción colaborativa, a través de una posición empática del terapeuta, dirigida al reconocimiento de los estados internos del paciente. A pesar del trabajo colaborativo, la resistencia también surgió como un patrón repetitivo. El terapeuta se volvió directivo con intervenciones estructuradas cuestionando al paciente, contribuyendo así al desarrollo de la capacidad mentalizadora. Se presentan implicaciones en el proceso psicoterapéutico e indicaciones para futuros estudios con el objetivo de contribuir a la comprensión del tratamiento de pacientes con tlp en psicoterapia psicodinámica.

Interaction structures are repetitive patterns of interaction between therapist and patient, even if they are not conscious of it. In empirical research, they help to un-derstand how the process of change in psychotherapy is established. In this sense, the current research used 68 sessions of psychoanalytic psychotherapy in a young patient with Borderline Personality Disorder (bpd) to identify the interaction structures and their correlation with different moments of treatment. The sessions were recorded on video and later encoded through the Psy-chotherapy Process Q-Set (PQS) by pairs of judges trained in Q-Sort methodology. A factor analysis of the Q-type of main components was performed based on these data, which indicated four interaction structures. Factor 1: Collaborative; factor 2: Resistance; factor 3: Alliance/Rupture; and factor 4: Support/Encornment. The structures indicated the interaction became a work of maintenance of the collaborative interaction through an empathic position of the therapist, focused on recognizing the patient's internal states. Despite the collaborative work, resistance also appeared as a repetitive pattern. The therapist became more directive with more structured interventions questioning the patient, thus, contributing to the development of the capacity of mentalization. Implications for the psychotherapeutic process and in-dications for future studies are presented to contribute to the comprehension of the treatment of patients with bpd in psychodynamic psychotherapy.

eHSP70/iHSP70 and divergent functions on the challenge: effect of exercise and tissue specificity in response to stress.

Heat-shock proteins including HSP70 are stress-related proteins that have been reported in cell protection and survival. In contrast to this, the increase in circulating levels of HSP70 (eHSP70) is associated with cellular damage and inflammatory factors. Physical stress, like exercise, is effective to induce both iHSP70 and eHSP70 in several tissues and cell types, which have different behaviours in response to stress. The different functions of HSP70 before the challenge are dependent of intracellular localization and subsequent molecular chaperone action, but when present in the extracellular space, it activates pro-inflammatory pathways. The different forms in which tissues and cells respond to stress like physical exercise, as well as the optimal intensity of the stress, are determinants for the beneficial effects or as an indicator of dangerous conditions, summoning immune cells as a warning sign to the body.

Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio.

Exercise stimulates immune responses, but the appropriate "doses" for such achievements are unsettled. Conversely, in metabolic tissues, exercise improves the heat shock (HS) response, a universal cytoprotective response to proteostasis challenges that are centred on the expression of the 70-kDa family of intracellular heat shock proteins (iHSP70), which are anti-inflammatory. Concurrently, exercise triggers the export of HSP70 towards the extracellular milieu (eHSP70), where they work as pro-inflammatory cytokines. As the HS response is severely compromised in chronic degenerative diseases of inflammatory nature, we wondered whether acute exercise bouts of different intensities could alter the HS response of lymphocytes from secondary lymphoid organs and whether this would be related to immunoinflammatory responses. Adult male Wistar rats swam for 20 min at low, moderate, high or strenuous intensities as per an overload in tail base. Controls remained at rest under the same conditions. Afterwards, mesenteric lymph node lymphocytes were assessed for the potency of the HS response (42 °C for 2 h), NF-κB binding activity, mitogen-stimulated proliferation and cytokine production. Exercise stimulated cell proliferation in an "inverted-U" fashion peaking at moderate load, which was paralleled by suppression of NF-κB activation and nuclear location, and followed by enhanced HS response in relation to non-exercised animals. Comparative levels of eHSP70 to iHSP70 (H-index) matched IL-2/IL-10 ratios. We conclude that exercise, in a workload-dependent way, stimulates immunoinflammatory performance of lymphocytes of tissues far from the circulation and this is associated with H-index of stress response, which is useful to assess training status and immunosurveillance balance.

Treatment and Prognosis of Facial Palsy on Ramsay Hunt Syndrome: Results Based on a Review of the Literature.

Introduction Ramsay Hunt syndrome is the second most common cause of facial palsy. Early and correct treatment should be performed to avoid complications, such as permanent facial nerve dysfunction. Objective The objective of this study is to review the prognosis of the facial palsy on Ramsay Hunt syndrome, considering the different treatments proposed in the literature. Data Synthesis We read the abstract of 78 studies; we selected 31 studies and read them in full. We selected 19 studies for appraisal. Among the 882 selected patients, 621 (70.4%) achieved a House-Brackmann score of I or II; 68% of the patients treated only with steroids achieved HB I or II, versus 70.5% when treated with steroids plus antiviral agents. Among patients with complete facial palsy (grades V or VI), 51.4% recovered to grades I or II. The rate of complete recovery varied considering the steroid associated with acyclovir: 81.3% for methylprednisolone, 69.2% for prednisone; 61.4% for prednisolone; and 76.3% for hydrocortisone. Conclusions Patients with Ramsay-hunt syndrome, when early diagnosed and treated, achieve high rates of complete recovery. The association of steroids and acyclovir is better than steroids used in monotherapy.

Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression.

OBJECTIVES: To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. METHODS: Adult obese patients (N = 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. RESULTS: In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH + F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. CONCLUSIONS: Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.