Neuronal responses to omitted tones in the auditory brain: A neuronal correlate for predictive coding.

Prediction provides key advantages for survival, and cognitive studies have demonstrated that the brain computes multilevel predictions. Evidence for predictions remains elusive at the neuronal level because of the complexity of separating neural activity into predictions and stimulus responses. We overcome this challenge by recording from single neurons from cortical and subcortical auditory regions in anesthetized and awake preparations, during unexpected stimulus omissions interspersed in a regular sequence of tones. We find a subset of neurons that responds reliably to omitted tones. In awake animals, omission responses are similar to anesthetized animals, but larger and more frequent, indicating that the arousal and attentional state levels affect the degree to which predictions are neuronally represented. Omission-sensitive neurons also responded to frequency deviants, with their omission responses getting emphasized in the awake state. Because omission responses occur in the absence of sensory input, they provide solid and empirical evidence for the implementation of a predictive process.

Adjunctive role of immunohistochemical expression of Nucleostemin in differentiation of grade II and III diffuse astrocytomas.

AIMS: Astrocytomas are common tumors and grade is an important parameter in determining the treatment modalities. Tumor proliferation activity should be determined for the differentiation of grades II and III tumors. In difficult cases, an auxiliary parameter is required. Nucleostemin (NS) is nucleolar Guanosine triphosphate (GTP)-binding protein 3. It has important roles in cell proliferation, cell cycle regulation, self-renewal, and apoptosis. In this study, we investigated whether the level of NS expression is different in grades II and III astrocytomas. SETTINGS AND DESIGN: Adults diagnosed with grades II and III astrocytomas were included in the study. MATERIAL AND METHODS: Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for NS. Only nuclear staining was evaluated; cytoplasmic staining was not considered. STATISTICAL ANALYSIS USED: Fisher's exact test, continuity corrections, and Pearson's Chi-square tests were used in the crosstabs. The survival analysis was based on the Kaplan-Meier method. RESULTS: Only 20% (6/30) of grade II tumors had high intensity staining, while 54,2% (13/24) of grade III tumors had high staining intensity. NS was significantly more intense in grade III tumors than grade II tumors. In cases with high NS expression, survival was significantly shorter than the cases with low expression. CONCLUSION: NS is significantly higher expressed in grade III tumors than grade II tumors. In difficult cases, it can be used as a useful proliferation marker in the differentiation of grades II and III astrocytomas.

Long-term BTX-A effects on bi-articular muscle: Higher passive force, limited length range of active force production and unchanged intermuscular interactions.

Botulinum toxin type-A (BTX-A) is commonly used for spasticity management aiming at reducing joint stiffness and increasing joint range of motion in CP patients. However, previous animal studies showed acutely increased passive forces and a narrowerlength range of active force exertion (lrange) for muscles exposed. BTX-A can spread affecting mechanics of several muscles in a compartment, but it was shown acutely to diminishepimuscular myofascial force transmission (EMFT). Yet, our understanding of these effects in the long-term is limited and they need to be tested in a bi-articular muscle. The goal was to test the following hypotheses in a long-term rat model: exposure to BTX-A (i) has no effects onlrangeand passive forces of bi-articular extensor digitorum longus (EDL) muscle and (ii) diminishes EMFT. Male Wistar rats were divided into two groups: BTX-A and control (0.1 units of BTX-A or only saline was injected into the tibialis anterior). Isometric proximal and distal EDL forces were measured simultaneously, one-month post-injection. Proximally and distally lengthening the muscle showed that BTX-A causes a significantly narrowerlrange(by 14.7% distally and 32.2% proximally) and significantly increased passive muscle forces (over 2-fold both distally and proximally). Altering muscle position at constant length showed that BTX-A does not change EMFT. The findings reject both hypotheses showing that long-term exposure to BTX-A compromises bi-articular muscle's contribution to motion for both joints and the muscle's mechanical interaction with the surroundings remains unaffected. These effects which may compromise long-term spasticity management should be studied in CP patients.

Long-Term Effects With Potential Clinical Importance of Botulinum Toxin Type-A on Mechanics of Muscles Exposed.

Botulinum toxin type-A (BTX-A) is widely used for spasticity management and mechanically aims at reducing passive resistance at the joint and widening joint range of movement. However, recent experiments on acute BTX-A effects showed that the injected rat tibialis anterior (TA) muscle's passive forces increased, and the length range of active force exertion (l range) did not change. Additionally, BTX-A was shown to spread into non-injected muscles in the compartment and affect their mechanics. Whether those effects persist in the long term is highly important, but unknown. The aim was to test the following hypotheses with experiments conducted in the anterior crural compartment of the rat: In the long term, BTX-A (1) maintains l range, (2) increases passive forces of the injected TA muscle, and (3) spreads into non-injected extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles, also affecting their active and passive forces. Male Wistar rats were divided into two groups: BTX-A and Control (0.1 units of BTX-A or only saline was injected into the TA). Isometric forces of the muscles were measured simultaneously 1-month post-injection. The targeted TA was lengthened, whereas the non-targeted EDL and EHL were kept at constant length. Hydroxyproline analysis was done to quantify changes in the collagen content of studied muscles. Two-way ANOVA test (for muscle forces, factors: TA length and animal group) and unpaired t or Mann-Whitney U test (for l range and collagen content, where appropriate) were used for statistical analyses (P < 0.05). BTX-A caused significant effects. TA: active forces decreased (maximally by 75.2% at short and minimally by 48.3%, at long muscle lengths), l range decreased (by 22.9%), passive forces increased (by 12.3%), and collagen content increased (approximately threefold). EDL and EHL: active forces decreased (up to 66.8%), passive force increased (minimally by 62.5%), and collagen content increased (approximately twofold). Therefore, hypothesis 1 was rejected and 2 and 3 were confirmed indicating that previously reported acute BTX-A effects persist and advance in the long term. A narrower l range and an elevated passive resistance of the targeted muscle are unintended mechanical effects, whereas spread of BTX-A into other compartmental muscles indicates the presence of uncontrolled mechanical effects.

Protective effects of melatonin on lung damage associated with one-lung ventilation: An experimental study.

BACKGROUND: This study aims to investigate the protective effect of melatonin on lung damage induced by one-lung ventilation in a rat model. METHODS: A total of 20 healthy, Sprague-Dawley male rats were randomized into two equal groups as control (n=10) and melatonin groups (n=10). The control group underwent 60 min of one-lung ventilation, followed by 30 min of two-lung ventilation. In the melatonin group, the rats were administered 10 mg/kg melatonin intraperitoneally 10 min before the start of the experiment. At the end of both ventilation periods, tissue samples were obtained from the lungs of the control and melatonin groups for biochemical analysis and histopathological examinations. Tissue superoxide dismutase, malondialdehyde, and tumor necrosis factor-alpha levels were measured. Lung tissue samples were examined based on the presence and amount of alveolar congestion, intra-alveolar bleeding, and leukocyte and lymphocyte infiltration. RESULTS: At the end of the study, lung tissue malondialdehyde (3.8±0.9 vs. 1.8±0.8 µM; p<0.001) and tumor necrosis factor-alpha levels (47.2±15.0 vs. 21.8±7.2 pg/mL; p<0.001) of the melatonin group were found to significantly decrease, compared to the control group. Superoxide dismutase levels of the melatonin group increased at the end of both ventilation periods, and the increase at the end of one-lung ventilation was found to be statistically significant (0.6±0.2 vs. 1.3±0.7 U/mL; p<0.05). Histopathological examination demonstrated that the tissue damage was less in the melatonin group. There was a significant decrease in the alveolar congestion in this group (p=0.0401). Although other histopathological parameters decreased in the melatonin group, no significant difference was found. CONCLUSION: Our study results demonstrate that melatonin has protective effects on the lung damage induced by one-lung ventilation both at biochemical and histopathological levels in rats.

Clinical, Histochemical, and Molecular Study of Three Turkish Siblings Diagnosed with H Syndrome, and Literature Review.

BACKGROUND: The term "H syndrome" was coined to denote the major clinical findings, which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hyperglycaemia, hypogonadism, hallux flexion contractures, and short height. OBJECTIVE: To report the clinical, endocrinological, histochemical, and genetic findings of three siblings. METHODS: Skin and liver biopsies were taken to investigate the histochemical characteristics of hyperpigmented hypertrichotic skin lesions and massive hepatomegaly. The levels of basal serum thyroid hormones, oestradiol, total testosterone, follicle-stimulating hormone, luteinising hormone, and stimulated growth hormone (GH) were measured to investigate the endocrine aspects of the syndrome. Mutation analysis was carried out in all six exons and exon-intron boundaries of SLC29A3 by direct sequencing. RESULTS: Physical examination of the patients revealed common charac-teristic findings of H syndrome. Additional clinical findings were sectorial iris atrophy in the younger sister. Laboratory evaluation revealed microcytic anaemia, markedly increased erythrocyte sedimentation rate and C-reactive protein levels, and humoral immune deficiency in the younger siblings, who presented with recurrent fever and sinopulmonary infection. Two different GH stimulation tests revealed GH deficiency in the younger sister with short stature. Liver and skin biopsies revealed polyclonal lymphohistiocytic and plasma cell infiltration. Sequencing of SLC29A3 in the three siblings revealed a novel homozygous mutation in exon 6, which caused the transition of arginine to tryptophan. CONCLUSION: This study not only extended the clinical and mutation spectrum of SLC29A3 in H syndrome, but also showed that short children should be assessed according to the guidelines for short stature in children.

Water-Clear Cell Adenoma of the Mediastinal Parathyroid Gland.

Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.

Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease: case-based review.

In rheumatology practice, the risk of hepatotoxicity from medications, including non-steroidal anti-inflammatory drugs, notably, and methotrexate, sulfasalazine, leflunomide, and azathioprine is highly recognized by the rheumatologists. On the other hand, hepatotoxicity is neither a commonly expected nor a well-known side effect of cyclophosphamide (CYC) which is particularly used for vital organ involvements in systemic lupus erythematosus (SLE) and systemic vasculitis. Here we reported a 19-year-old case of SLE who, while on oral CYC treatment of 100 mg/day, was detected to have asymptomatic liver enzyme elevation and then developed acute hepatitis due to intravenously administered high-dose (1 g) CYC for neuro-lupus. Results of liver biopsy indicated drug-related toxicity. We discussed here with the other, although rare, cases available in the literature with an attempt to highlight the risk of hepatotoxicity and acute hepatitis due to CYC.

Nephrogenic adenoma of the urinary tract: A 6-year single center experience.

BACKGROUND: Nephrogenic adenoma is an uncommon benign lesion that occurs at several sites in urinary tract, from the renal pelvis to urethra, with the highest frequency in urinary bladder. Nephrogenic adenoma displays a broad spectrum of architectural and cytological features. Hence, recognition of its characteristic histopathological features is needed to distinguish this lesion from its mimickers. MATERIALS AND METHODS: A retrospective series of 21 cases of nephrogenic adenoma in 18 patients, which were diagnosed in our department between 2010 and 2016, were analyzed. All histological slides were reviewed by two pathologists and the diagnosis of each case was confirmed. Immunohistochemistry was performed for PAX-8 in all cases. CK7, PAX-2, PSA, p53, p63, GATA-3 and α-methylacyl-CoA racemase (AMACR) were applied in problematic cases. RESULTS: The most common location of the lesion was urinary bladder (14 patients) followed by renal pelvis (2 patients), ureter (1 patient) and urethra (1 patient). A history of urothelial carcinoma and repeated TUR procedures were observed in 12 patients. There were 2 pediatric patients aged 3 years. Both of them had undergone previous urosurgery because of megaureter in one and bladder exstrophy in the other. Other clinical antecedents included bladder diverticulum (1 patient), cystitis (1 patient) and nephrolithiasis (1 patient). Recurrence of lesion was seen in two patients (once in one case and twice in the other one). The median time to disease recurrence in these patients was 11 months (range, 2-20 months). Histologically, the lesions exhibited various morphological findings, with mixed (15 cases, 71.4%), pure tubular (3 cases, 14.3%), pure papillary (2 cases, 9.5%) and pure flat (1 case, 4.8%) growth patterns. Of the 15 cases with mixed patterns, 8 cases were tubulocystic and flat, 3 cases were tubular and flat, 2 cases were tubular, papillary and flat, 1 case was tubulocystic, papillary and flat, and 1 case was tubular and papillary. Flat pattern was observed in 15 cases (71.4%). It was seen in association with other patterns in 14 cases (mixed morphology) and purely in 1 case. Our findings suggested that the flat pattern is a frequent finding in nephrogenic adenomas. Notably one case in this series showed superficial extension into bladder muscularis propria. CONCLUSIONS: Histologically nephrogenic adenoma may simulate a variety of malignancies. Awareness of characteristic morphologic features of nephrogenic adenoma is needed to diagnose this lesion correctly.

Inflammatory cloacogenic polyp: a rare kind of benign polyp to be cured with endoscopic and/or surgical removal / Pólipo cloacogênico inflamatório: um raro tipo de pólipo benigno a ser curado por remoção endoscópica e/ou cirúrgica

Abstract Background Inflammatory cloacogenic polyp is a very rare kind of benign polyp which occurs in the anal transitional zone and lower rectum. These polyps arise in association with various conditions (e.g., internal hemorrhoids, diverticulosis, colorectal tumors, and Crohn's disease) in which mucosal injury is the underlying pathogenic mechanism. Case report A 24-year-old male patient applied to emergency department with bloody defecation for a month. A polyp that is 1.5 cm in size had been observed at rectum and anal verge junction during colonoscopy, pathological diagnosis was inflammatory cloacogenic polyp. Thereupon, colonoscopic polypectomy was performed as the malignant transformation possibility. Conclusion Polyps of the anorectal junction with inflammatory appearance might be inflammatory cloacogenic polyps with malignant transformation potential that must be treated by endoscopic removal or surgery and followed up routinely with colonoscopic surveillance.

Resumo Experiência Pólipos cloacogênicos inflamatórios constituem um tipo muito raro de pólipo benigno, com ocorrência na zona de transição anal e reto baixo. Esses pólipos surgem em associação com diversos distúrbios (p. ex., hemorroidas internas, diverticulose, tumores colorretais, e doença de Crohn) nos quais a lesão à mucosa é o mecanismo patogênico subjacente. Relato de caso Paciente, gênero masculino, 24 anos, compareceu ao serviço de emergência com defecação sanguinolenta com duração de um mês. Durante a colonoscopia, foi observado um pólipo medindo 1,5 cm de diâmetro no reto e na junção da borda anal; foi estabelecido um diagnóstico patológico de pólipo cloacogênico inflamatório. Subsequentemente, foi realizada polipectomia colonoscópica, diante do potencial de transformação maligna. Conclusão Pólipos da junção anorretal com aspecto inflamatório podem ser pólipos cloacogênicos inflamatórios com potencial para transformação maligna, devendo ser tratados por remoção endoscópica ou cirúrgica e monitorados periodicamente com vigilância colonoscópica.

Tumor deposits: Prognostic significance in gastric cancer patients.

PURPOSE: Tumor deposits (TDs) are defined as satellite peritumoral nodules in the peritumoral adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule. We aimed to investigate the relation between TDs and clinicopathological characteristics of gastric cancer and to evaluate the effect of TDs on prognosis. METHODS: One hundred and seven non-metastatic gastric cancer patients were enrolled. The relationships between positive and negative TDs with respect to clinicopathological characteristics, as well as disease free survival (DFS) and overall survival (OS), were analyzed. RESULTS: TDs were detected in 28 patients (26.2%). Advanced pT stage and pN stage were significantly higher in TDs-positive compared to TDs-negative patients (p=0.015 and p=0.037, respectively). No significant differences were identified between the groups in other clinicopathological variables such as gender, lymphovascular and perineural invasion. Recurrence and mortality rates were higher in the TDs-positive patients during follow-up of both groups (22/78.6% vs 38/48.1%, p=0.010 for relapse; 20/71.4% vs 3/38%, p=0.005 for mortality). The univariate analysis demonstrated shorter DFS and OS for TDs-positive compared to TDs-negative patients. In multivariate analysis, TDs-positive patients had 1.75-fold higher likelihood to develop recurrence, while the likelihood of death increased 1.99-fold (p=0.041 and p=0.020, respectively). CONCLUSION: TDs-positive gastric cancers demonstrate a more aggressive clinical course compared to TDs-negative. More effective treatment methods should be necessary for management of this subgroup of gastric cancer.