An update on oral peripheral nerve sheath tumors.

Peripheral nerve sheath tumors (PNSTs) are defined as type of sarcomas that develops in cells which forms a protective sheath (covering) around the peripheral nerve, i.e., the cells of myelin sheath. Nerve tumors are of neuroectodermal in origin as it was composed of small rounded ectodermal cells that affect exclusively soft tissues. PNSTs are most common neoplasm with classic clinicopathological features, but they are diagnostically challenging. They consist of wide spectrum of tumors ranging from benign tumors to malignant nerve sheath tumors and its prevalent in oral tissues. Diagnosis of PNSTs are quite hectic but made possible by histopathology and immunohistological markers.

CTCAE versión 5.0. Evaluación de la gravedad de los eventos adversos dermatológicos de las terapias antineoplásicas / Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies

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Osteodystrophies of jaws.

Bone is a dense, semi rigid, porous, calcified connective tissue forming the major portion of the skeleton of most vertebrates. It consists of a dense organic matrix and an inorganic mineral component. Bone remodelling is a complex process by which old bone is continuously replaced by new tissue, which requires interaction between different cell phenotypes and is regulated by a variety of biochemical and mechanical factors. In a homeostatic equilibrium, the process of resorption and formation are balanced so that old bone is continuously replaced by new tissue and it adapts to mechanical load and strain. Several local and systematic factors which cause disturbances in bone resorption and deposition leads to abnormal or defective development of bone commonly termed as osteodystrophy - A defective ossification of bone usually is associated with disturbed calcium and phosphorus metabolism. The better understanding of molecular cellular biology and pathogenic mechanism aids to define the abnormalities in osteoblastic and osteoclastic lineages and to develop new therapeutic approaches.

Feasibility of a deep hyperthermia and radiotherapy programme for advanced tumors: first Spanish experience.

BACKGROUND: Hyperthermia (HT) is used to increase the temperature of the tumor-sensitizing cells to the effects of radiation/chemotherapy. We aimed to assess the feasibility, tolerability and safety of hyperthermia treatment in a Radiation Oncology Department. METHODS: Between June 2015 and June 2017, 106 patients and a total of 159 tumor lesions were included in a prospective study (EudraCT 2018-001089-40) of HT concomitant with radiotherapy (RT). Systemic treatment was accepted. HT was given twice a week, 60 min per session, during RT treatment by a regional capacitive device (HY-DEEP 600WM system) at 13.56 MHz radiofrequency. RESULTS: Most lesions (138 cases, 86.8%) received all HT sessions planned. Thirteen lesions (12 patients) withdrew treatment due to grade ≥3 QMHT toxicity. All these 12 patients completed the prescribed radiotherapy and/or systemic treatment. CONCLUSIONS: Regional hyperthermia is a feasible and safe technique to be used in combination with radiotherapy and systemic treatment.

In vivo glutamate clearance defects in a mouse model of Lafora disease.

Lafora disease (LD) is a fatal rare neurodegenerative disorder characterized by epilepsy, neurodegeneration and insoluble polyglucosan accumulation in brain and other peripheral tissues. Although in the last two decades we have increased our knowledge on the molecular basis underlying the pathophysiology of LD, only a small part of the research in LD has paid attention to the mechanisms triggering one of the most lethal features of the disease: epilepsy. Recent studies in our laboratory suggested that a dysfunction in the activity of the mouse astrocytic glutamate transporter 1 (GLT-1) could contribute to epilepsy in LD. In this work, we present new in vivo evidence of a GLT-1 dysfunction, contributing to increased levels of extracellular glutamate in the hippocampus of a mouse model of Lafora disease (Epm2b-/-, lacking the E3-ubiquitin ligase malin). According to our results, Epm2b-/- mice showed an increased neuronal activity, as assessed by c-fos expression, in the hippocampus, an area directly correlated to epileptogenesis. This brain area presented lesser ability to remove synaptic glutamate after local GLT-1 blockade with dihydrokainate (DHK), in comparison to Epm2b+/+ animals, suggesting that these animals have a compromised glutamate clearance when a challenging condition was presented. These results correlate with a hippocampal upregulation of the minor isoform of the Glt-1 gene, named Glt-1b, which has been associated with compensatory mechanisms activated in response to neuronal stress. In conclusion, the hippocampus of Epm2b-/- mice presents an in vivo impairment in glutamate uptake which could contribute to epileptogenesis.

Effects of Hallucinogens on Neuronal Activity.

Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2-4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

How can information on the risk of breast cancer and hormone therapy be better understood?

OBJECTIVES: To evaluate postmenopausal women's knowledge of the risk of breast cancer associated with the use of hormone therapy (HT) and their perception of this risk when presented as a relative risk (RR), absolute risk (AbR) or attributable risk (AR). METHODS: A cross-sectional study was conducted with 402 postmenopausal women. The participants answered a self-response questionnaire in which data on the risk of breast cancer associated with HT were presented in the form of RR, AbR and AR. The women's concern with respect to this risk and their changes of opinion when the data were presented according to the different risk models were evaluated. RESULTS: More than 87% of the women mentioned breast cancer as one of the risks associated with the use of HT, with more women being concerned when the risk was presented as an RR. In contrast, most were unconcerned when the risk was presented as an AbR or AR. For the group as a whole, there was a significant change in opinion with respect to the women's concern regarding the risks when they were presented as an AbR or AR (p < 0.001); however, this was not the case for those women who had initially stated that breast cancer was a risk associated with HT. CONCLUSIONS: Providing information on breast cancer risk using examples that quantify the incidence of the disease provokes less concern in users and candidate users of HT. Changes of opinion occur when explanations regarding the risk are provided as RR, AbR and AR.

Relationship between femur bone mineral density, body mass index and dental panoramic mandibular cortical width in diagnosis of elderly postmenopausal women with osteoporosis.

OBJECTIVES: To measure and determine mandibular cortical width (MCW) on the panoramic radiographs, to evaluate the usefulness of the method in identifying postmenopausal women with low femoral bone mineral densities (f- BMD) and to correlate the radiographic findings on panoramic radiographs with the f-BMD assessed by dual X-ray absorptiometry (DXA) to predict the efficacy of the radiographic method in diagnosing osteoporosis. MATERIALS AND METHODS: One hundred and twenty postmenopausal women (60 normal and 60 osteoporotic) in the age group of 50-75 y with f-BMD assessed by DXA had undergone panoramic radiographic examination. The patients were classified as normal (T-score ≥ -1.0) and osteoporotic (T-score ≤ -2.5). MCW on panoramic radiographs was measured bilaterally at the mental foramen region with a caliper and their mean was used as the exposure measure in the analysis. RESULTS: Student t-test showed that mean f-BMD, BMI and MCW was found be less in osteoporotic patients as compared to normal group with a statistically significant p-value < 0.001. Pearson correlation coefficient test revealed that MCW correlated positively with f-BMD and showed a significant decrease with age of the patient. CONCLUSION: Postmenopausal women with low f-BMD had thinner mandibular cortex at the mental foramen region when compared to normal subjects and are more susceptible to femoral neck fractures. Mandibular inferior cortical width at the mental foramen region could be used to identify postmenopausal women with low f- BMD. Hence, dental panoramic radiographs serve as a useful screening tool for early diagnosis of osteoporotic fractures.

Contraception for women with heart disease.

There is a lack of studies dealing specifically with contraceptive use in women with heart disease. This may generate doubts in professionals counseling on the patient's risk of pregnancy as a function of her cardiomyopathy. Moreover, uncertainties may arise with respect to the optimal contraceptive choice for each individual case. In view of the increasing number of women of reproductive age with cardiac disease, this review aims at providing practical guidance for clinicians, including cardiologists, obstetricians, general practitioners and family planning specialists, with regards to safe contraceptive choices and counseling on the risk of pregnancy in women with heart disease.

Incidence of cystic changes in impacted lower third molar.

OBJECTIVE: To assess the incidence of cystic changes in the impacted lower third molar (ILTM) in which the pericoronal (follicular) space is less than 2.5 mm as measured from the radiograph. The relationship between the cystic changes and patient's age, sex, and angular position and contact of ILTM with adjacent tooth was also evaluated. MATERIALS AND METHODS: Follicular space less than 2.5 mm as measured from the panoramic radiograph was included in the study. A total of 73 tissue samples collected during the extraction ILTM were examined histopathologically. Then the data were analyzed for associations with age, sex, angular position, and contact of the ILTM with an adjacent tooth. RESULTS: There were 37 male and 36 female patients, age ranging from 17 to 35 years (mean 23.95 years). Out of 73 specimens, 17 (23.3%) showed cystic changes; among them 16 (22.1%) showed dentigerous cysts and 1 (1.2%) showed odontogenic keratocysts. Most of the cystic changes occurred in the 26-30 year age range. The cystic changes showed male predominance but could not gain statistical significance. The relationship between cystic changes and angular position was statistically significant (P < 0.05). Higher probability was found in distoangular positioned ILTM. The relationship between cystic changes and communication of ILTM with the second molar was not statistically significant. CONCLUSION: Incidence of cystic changes in ILTM justifies extraction of the impacted tooth associated with symptoms. The decision to extract or not to extract impacted third molar should be individualized, rather than generalized.

Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action.

Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT(2A) receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.

Oral and salivary changes among renal patients undergoing hemodialysis: A cross-sectional study.

We wanted to assess oral and salivary changes in end stage renal disease (ESRD) patients undergoing hemodialysis (HD) and to understand the correlation of such changes with renal insufficiency. The cross-sectional study was performed among 100 ESRD patients undergoing HD. Among these, 25 patients were randomly selected to assess the salivary changes and compared with 25 apparently healthy individuals who formed the control group. Total duration of the study was 15 months. Oral malodor, dry mouth, taste change, increased caries incidence, calculus formation, and gingival bleeding were the common oral manifestations. The flow rates of both unstimulated as well as stimulated whole saliva were decreased in the study group. The pH and buffer capacity of unstimulated whole saliva was increased in the study group, but stimulated whole saliva did not show any difference. ESRD patients undergoing HD require special considerations during dental treatment because of the various conditions inherent to the disease, their multiple oral manifestations and the treatment side-effects.

Influence of the AT(2) receptor on the L-arginine-nitric oxide pathway and effects of (-)-epicatechin on HUVECs from women with preeclampsia.

Pregnancy is a state of vasodilation mediated by nitric oxide (NO). This vasodilation is impaired in women with preeclampsia, and an alteration in the L-arginine-NO pathway may be a causal factor. The production of NO and arginase activity were investigated in plasma and human umbilical vein endothelial cells (HUVECs) from women with preeclampsia, which were associated with arginase II, eNOS, caveolin, angiotensin 1 and 2 receptor expression (AT1R and AT2R, respectively). The effect of (-)-epicatechin on arginase activity and production of anion superoxide in HUVEC also were investigated. Healthy volunteer non-pregnant (HV), normal pregnant (NP) and preeclamptic (PE) women were recruited for this study. Higher values of nitrite/nitrate (NO(2)/NO(3)) were detected in the plasma from PE women as opposed to HV and NP. Lower arginase activity in PE versus HV or NP women was observed. HUVECs from PE women showed lower values of NO(2)/NO(3), higher activity of arginase and higher expression of AT(1)R and AT(2)R than HUVECS from NP women. Interestingly, arginase activity was associated with AT(2)R stimulation; indeed this activity and the high NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activity in HUVECs from PE women can uncouple the production or inactivation of NO. However, we demonstrated that (-)-epicatechin could lead to a decrease in the activity of both enzymes.

Furosemide is associated with acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients. Diuretics are used without any evidence demonstrating a beneficial effect on renal function. The objective of the present study is to determine the incidence of AKI in an intensive care unit (ICU) and if there is an association between the use of furosemide and the development of AKI. The study involved a hospital cohort in which 344 patients were consecutively enrolled from January 2010 to January 2011. A total of 132 patients (75 females and 57 males, average age 64 years) remained for analysis. Most exclusions were related to ICU discharge in the first 24 h. Laboratory, sociodemographic and clinical data were collected until the development of AKI, medical discharge or patient death. The incidence of AKI was 55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI = 1.57-6.80, and age: OR = 1.02 (95%CI = 1.00-1.04). Analysis of the subgroup of patients with septic shock showed that the odds ratio of furosemide was 5.5 (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic shock were predictors of AKI in critically ill patients. Use of furosemide in the subgroup of patients with sepsis/septic shock increased (68.4%) the chance of development of AKI when compared to the sample as a whole (43.9%).

Furosemide is associated with acute kidney injury in critically ill patients.

Acute kidney injury (AKI) is common in critically ill patients. Diuretics are used without any evidence demonstrating a beneficial effect on renal function. The objective of the present study is to determine the incidence of AKI in an intensive care unit (ICU) and if there is an association between the use of furosemide and the development of AKI. The study involved a hospital cohort in which 344 patients were consecutively enrolled from January 2010 to January 2011. A total of 132 patients (75 females and 57 males, average age 64 years) remained for analysis. Most exclusions were related to ICU discharge in the first 24 h. Laboratory, sociodemographic and clinical data were collected until the development of AKI, medical discharge or patient death. The incidence of AKI was 55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI = 1.57-6.80, and age: OR = 1.02 (95%CI = 1.00-1.04). Analysis of the subgroup of patients with septic shock showed that the odds ratio of furosemide was 5.5 (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic shock were predictors of AKI in critically ill patients. Use of furosemide in the subgroup of patients with sepsis/septic shock increased (68.4%) the chance of development of AKI when compared to the sample as a whole (43.9%).

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects.

Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.