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Background: The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms., Methods: We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive., Results: Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p  = 0.0001, Cohen's d  = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p  < 0.0001, d  = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p  < 0.0001, d  = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons., Conclusion: We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population., Clinical Trial Registration: clinicaltrials.gov, identifier NCT02642029., Competing Interests: JC is a member of the scientific advisory board of Hyka and Flow Neuroscience and has been a consultant for Mifu Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shinn, Hurtado-Puerto, Roh, Ho, Hwang, Cohen, Öngür and Camprodon.)

Background: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI)., Methods: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18 F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31 P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow., Conclusion: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.

Purpose: The cerebellum is an intricate neural structure that orchestrates various cognitive and behavioral functions. In recent years, there has been an increasing interest in neuromodulation of the cerebellum with transcranial magnetic stimulation (TMS) for therapeutic and basic science applications. Theta burst stimulation (TBS) is an efficient and powerful TMS protocol that is able to induce longer-lasting effects with shorter stimulation times compared with traditional TMS. Parameters for cerebellar TBS are traditionally framed in the bounds of TBS to the cerebral cortex, even when the 2 have distinct histologic, anatomical, and functional characteristics. Tolerability limits have not been systematically explored in the literature for this specific application. Therefore, we aimed to determine the stimulation parameters that have been used for cerebellar. TBS to date and evaluate adverse events and adverse effects related to stimulation parameters., Methods: We used PubMed to perform a critical review of the literature based on a systematic review of original research studies published between September 2008 and November 2019 that reported on cerebellar TBS. We recovered information from these publications and communication with authors about the stimulation parameters used and the occurrence of adverse events., Findings: We identified 61 research articles on interventions of TBS to the cerebellum. These articles described 3176 active sessions of cerebellar TBS in 1203 individuals, including healthy participants and patients with various neurologic conditions, including brain injuries. Some studies used substantial doses (eg, pulse intensity and number of pulses) in short periods. No serious adverse events were reported. The specific number of patients who experienced adverse events was established for 48 studies. The risk of an adverse event in this population (n = 885) was 4.1%. Adverse events consisted mostly of discomfort attributable to involuntary muscle contractions. Authors used a variety of methods for calculating stimulation dosages, ranging from the long-established reference of electromyography of a hand muscle to techniques that atone for some of the differences between cerebrum and cerebellum., Implications: No serious adverse events have been reported for cerebellar TBS. There is no substantial evidence of a tolerable maximal-efficacy stimulation dose in humans. There is no assurance of equivalence in the translation of cortical excitability and stimulation intensities from the cerebral cortex to cerebellar regions. Further research for the stimulation dose in cerebellar TBS is warranted, along with consistent report of adverse events. © 2020 Elsevier HS Journals, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

Objective: Chronic visceral pain (CVP) syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG) and on pain perception, through clinical tests., Design: A pilot crossover randomized controlled study., Settings: Out-patient., Subjects: Adults with CVP (>3 months)., Methods: Participants received four interventions in a randomized order: (1) transcranial pulsed current stimulation (tPCS) and active transcranial direct current stimulation (tDCS) combined, (2) tPCS alone, (3) tDCS alone, and (4) sham condition. Resting state quantitative electroencephalography (qEEG) and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls., Results: We enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths., Conclusion: This study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

Introduction: The study of the structure in the arterial wall has been essential to use vessels in the coronary and cerebral bypass. The superficial temporal artery, owing to its high elastic content and its topography, close to the middle cerebral artery, has made possible the revascularization surgery in cerebral areas with ischemia. AIM. The purpose of this study is define the structure of the superficial temporal artery., Material and Methods: The material of the present study are 60 arteries from medico legal necropsies without apparent vascular pathology. Pieces were fixed in 10% formol, embedded in Paraplast, sectioned in sequence of 7 mm and were stained to detect elastic, collagen and reticulin fibers. Histochemical techniques have been done too., Results: The superficial temporal artery shows a high elastic content, above all in the middle outer of the tunica media. The negative aspect is the great quantity of collagen in this tunica, that produces the progressive hardness of this vessel with the increase of the age. Histochemistry shows how the accumulation of acid mucosubstances interferes in the correct nourishing of the internal elastic membrane, that is disorganized in the cushions., Conclusion: The superficial temporal artery is an appropriate vessel to the coronary and cerebral bypass, due to its high elastic content in this tunica and the limitants. It have not been observed in our material zones without internal elastic membrane. Histochemistry shows abundant acid mucosubstances that difficult the nourishing in the arterial wall.

We investigated the contribution of reactive oxygen species to the development of sebaceous gland hyperplasia and the characteristics of the glutathione S-transferase/glutathione system in male pattern baldness. Glutathione S-transferase, glutathione, and thiobarbituric acid-reactive substances were determined in sebaceous gland-enriched scalp skin of men affected by male pattern baldness and were subjected to hair autotransplantation. In comparison with the hairy occipital-donor areas, the following results were obtained in alopecic frontoparietal samples: glutathione S-transferase-specific activity increased 7-fold (p < 0.001); enzyme affinity towards 1-chloro-2,4-dinitrobenzene decreased 2-fold (p = 0.009); glutathione content decreased 2.5-fold (p = 0.017); and thiobarbituric acid reactive substances increased 2-fold (p = 0.006). Chromatofocusing analysis, bromosulfophthalein IC50 values, enzyme-linked immunosorbent assay, and immunohistochemistry with polyclonal antibodies raised against glutathione S-transferases alpha, mu, and pi demonstrated the presence of alpha, pi, and probably the 5.8 alpha isoenzymes in the sebaceous gland. These results support the hypothesis that reactive oxygen species are involved in the pathogenesis of sebaceous gland hyperplasia in male pattern baldness.

Background: Erythrocytic glutathion S-transferase (GST) plays an important role as a protective mechanism against oxidative stress. The present study was conducted to evaluate the influence of both smoking habit and sex upon the kinetic characteristics of the enzyme., Subjects and Methods: 176 healthy subjects (100 men and 76 women), smokers and nonsmokers, were included. Enzyme parameters were calculated in erythrocytic haemolysates using 1-chloro-2,4-dinitrobenzene (CDNB) and glutathion (GSH) as substrates. Haemoglobin (Hb) was removed by affinity chromatography. In samples coming from 51 men and 42 women the native haemolysate was subjected to thermal shock (52 degrees C) and the enzyme parameters were compared with those obtained in the non-denatured samples., Results: In non-denatured samples, Km (mM) and Vmax (mumol/min/g Hb) values for CDNB were significantly higher (p < 0.001) in smokers than in non smokers, especially in women. Thus, respectively for Km and Vmax (mean +/- standard deviation): for men non smokers, 1.43 +/- 0.54, 1.63 +/- 0.42 and smokers, 1.74 +/- 0.5, 1.8 +/- 0.69; for women, non smokers 1.42 +/- 0.56, 1.57 +/- 0.46 and smokers, 2.05 +/- 0.59, 2.51 +/- 0.6. Thermal denaturation diminished the enzyme activity in all cases and modified the Km values, these results were opposite to those obtained in the non-denatured samples. Thus, for Km and Vmax respectively: for men, smokers, 1.6 +/- 0.71 and 0.9 +/- 0.32 and non smokers, 1.4 +/- 0.66 and 0.53 +/- 0.29; for women, non smokers, 2.00 +/- 0.58, 1.13 +/- 0.29 and smokers 1.22 +/- 0.77, 0.52 +/- 0.23. The GSt content was similar in the four groups studied (3.75 +/- 1.15 mumol SH/g Hb)., Conclusions: The greater thermolability of GST activity and the increase in the Km values observed in smokers, especially in women, should be considered as indicative of an increased risk for the erythrocytes against oxidative stress.

Pregnant rats were treated with benzo(a)pyrene (BP) (50 mg/kg every 2 days) from day 7 of pregnancy and killed at day 16 or day 19. Km of erythrocyte glutathione S-transferase (GST) decreased during pregnancy in control rats (1.29 x 10(-3) M at day 16; 1.02 x 10(-3) M at day 19) and even more in treated rats at day 19 (0.71 x 10(-3) M). Vmax was lower in treated rats at day 19 (0.56 mumol/min/g haemoglobin) than in control rats (0.88 mumol/min/g haemoglobin) suggesting inhibition of the enzyme. Placental weight diminished in treated rats at day 19 but was not affected at day 16. Chromatofocusing of placental GST showed a single peak (pH 8.3-8.6) in control and treated rats on day 16 and an additional peak (pH 7.0-7.4) in treated rats on day 19. An increase in Km (2.84 x 10(-3) M) and Vmax (69 nmol/min/mg protein) in placental GST was observed in treated rats at day 16 (Km = 1.61 x 10(-3) M; Vmax = 43.3 nmol/min/mg protein, in control rats) followed by a decrease in these parameters in rats treated until day 19 (Km = 1.63 x 10(-3) M; Vmax = 48.7 nmol/min/mg protein). These results suggest that BP, initially, stimulates GST synthesis in placenta, followed by an inhibition of the enzyme at day 19. Fetal weight was also affected by BP treatment, especially at day 16. Km and Vmax values of fetal GST were higher in treated rats at day 16 than in control rats but these differences were not detectable at day 19. This may be explained by the more protective role of the placenta at day 19 than at day 16. Glutathione content in erythrocytes, placenta and fetus was not affected by BP.

Glutathione S-transferase (GST) has been quantified and characterized in healthy human anagen hair follicles obtained from 36 men and 36 women (26 +/- 7 years of age). GST activity was determined using 1-chloro-2,4-dinitrobenzene as a substrate, and the values in men were: 0.5 +/- 0.2 mU/follicle, significantly different from women (0.36 +/- 0.2 mU/follicle); 196 +/- 98 mU/mg protein and 309 +/- 158 mU/mg DNA without significant differences from women. Enzyme activity showed a high degree of inter-individual variability (23.5-fold when expressed per follicle, 18.29-fold expressed per mg of protein and 22.75-fold per mg of DNA) in the whole population and this variability was higher in women. Ion-exchange chromatography by KCl and enzyme immunoassay suggest that the GST present in hair follicles corresponds with the acidic form. The percentage of anagen hairs in each subject showed a positive correlation with the following parameters: GST/hair, GST/DNA and DNA/hair. It is concluded that GST may contribute to the maintenance of the hair growth cycle.

Guanylate cyclase (GC) activity was measured in the cytosolic fraction of sebaceous gland-enriched skin samples obtained from alopecic and non-alopecic areas of subjects affected by male pattern baldness. GC activity was significantly higher in alopecic scalp (7.13 +/- 2.7 pmol/min/mg prot; n = 22) than in non-alopecic samples (3.91 +/- 0.48 pmol/min/mg prot; n = 8). 3-beta-androstanediol was able to increase GC activity up to 15% when added to the incubation medium (1 x 10(-5) M). The regional differences observed should be due to the larger size of the sebaceous glands in alopecic areas. The higher production of dihydrotestosterone and 3-beta-androstanediol in alopecic areas may also contribute to determine the level of GC in scalp skin. The role of second messenger systems in sebaceous glands to understand certain aspects of the action mechanism of androgens is discussed.

The consumption of antidiabetic drugs in a Spanish region (Extremadura) in the period 1986-1987 has been investigated by the "defined daily dose" (DDD) method. The study was done in three health care systems in the region: civil servants ("Mutualidad de Funcionarios Civiles del Estado: MUFACE") armed forces group ("Instituto Social de las Fuerzas Armadas: ISFAS") and the national system ("Instituto Nacional de la Salud: INSALUD"). The total consumption of antidiabetic drugs varied three-fold, ranging from 5,73 DDD per 1000 inhabitants per day (3,71 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 2,02 DDD per 1000 inhabitants per day for insulin) in the civil servant group to 15,82 DDD per 1000 inhabitants per day (12 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 3,82 DDD per 1000 inhabitants per day for insulins) in the armed forces. The differences were more pronounced for oral antidiabetics than for insulins. The utilization of insulin among the civil servants was about half of that by the two other groups. Of oral antidiabetics, sulphonylureas were the most frequently used by the three groups, and within them glibenclamide accounted for more than half of the DDDs, while biguanides were scarcely used in any group. The differences are difficult to assess, since they could be due to several factors, such as age-differences in the population studied, different prescribing habits, and differences in sociocultural level. The results justify further comparative studies of drug utilization in different health systems within the same region.

Regional differences in the androgen metabolism were established in alopecic and non alopecic areas of patients affected by male pattern baldness (MPB). 5-alpha-reductase (5-alpha-R) activity was measured by the formation of dihydrotestosterone (DHT), using 3H-testosterone as substrate: this activity was higher in the alopecic areas (3.4 pmol/g tissue/h) than in the non alopecic skin (1.5 pmol/g tissue/h). 3-alpha,beta-hydroxysteroid oxoreductase (3-alpha, beta-HO) was studied using 3H-DHT as precursor and measuring the corresponding formed 3-alpha- and 3-beta-androstanediols (alpha DIOL and beta DIOL). The beta DIOL was the predominant metabolite and total 3-alpha, beta-HO activity was higher in alopecic skin (12.4 pmol/g tissue/h) than in non alopecic areas (8.4 pmol/g tissue/h). Also 17, beta-hydroxysteroid oxoreductase was measured using either testosterone or DHT as substrates: androstenedione formed from testosterone was higher in hairy skin (12 pmol/g tissue/h) than in alopecic areas (6 pmol/g tissue/h); androstanedione formed from DHT was also higher in non alopecic areas (8.1 pmol/g tissue/h) than in alopecic skin (2.8 pmol/g tissue/h). The greater formation of beta DIOL in the sebaceous glands-enriched alopecic skin supports the hypothesis for a specific role of this metabolite in the control of the sebaceous activity.

Oxidative phenotype and metabolic ratio (MR) of debrisoquine (DBQ) have been determined in 87 patients with Parkinson's disease and in 556 healthy control subjects. Three patients (3.45%) and 34 control subjects (6.12%), having an MR greater than 12.6, were classified as poor metabolisers (PM) of DBQ (ns). The distribution of MR values in the 84 Parkinsonian patients classified as extensive metabolisers (EM) showed a less efficient oxidative rate when compared with controls of the same phenotype (p less than 0.001). This difference may be due to enzymatic inhibition caused by drug treatment in 40 of these patients. As in patients not taking any drug known to inhibit the oxidation of DBQ, distribution of MR values was not different from that in controls. A negative correlation (r = -0.36, p less than 0.02) was found between MR of DBQ and age at onset of disease in patients free of drugs known to interact with DBQ metabolism. A higher rate of DBQ oxidation could be a genetic factor that delays the clinical onset of Parkinson's disease in predisposed people.

Due to the importance of guided studies in training and improvement of workers hoping to reach the higher learning level, this new teaching modality is analyzed in the Higher Institute of Medical Sciences in Villa Clara in the discipline of Baccalaureate Nursing. Its advantages are described; the methodologic structure of the encounter course (as it is named from 1981 on as a result of the improvement of the teaching-educational process) is reported. Among these advantage the close association between teacher and student and self-training, which allows to develop the independent skills of the student are mentioned.