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The heterotrimeric G-protein α subunit, Gα olf , acts to transduce extracellular signals through G-protein coupled receptors (GPCRs) and stimulates adenylyl cyclase mediated production of the second messenger cyclic adenosine monophosphate. Numerous mutations in the GNAL gene, which encodes Gα olf , have been identified as causative for an adult-onset dystonia. These mutations disrupt GPCR signaling cascades in in vitro assays through several mechanisms, and this disrupted signaling is hypothesized to lead to dystonic motor symptoms in patients. However, the cells and circuits that mutations in GNAL corrupt are not well understood. Published patterns of Gα olf expression outside the context of the striatum are sparse, conflicting, often lack cell type specificity, and may be confounded by expression of the close GNAL homolog of GNAS. Here, we use RNAScope in-situ hybridization to quantitatively characterize Gnal mRNA expression in brain tissue from wildtype C57BL/6J adult mice. We observed widespread expression of Gnal puncta throughout the brain, suggesting Gα olf is expressed in more brain structures and neuron types than previously accounted for. We quantify transcripts at a single cell level, and use neuron type specific markers to further classify and understand patterns of GNAL expression. Our data suggests that brain regions classically associated with motor control, initiation, and regulation show the highest expression of GNAL, with Purkinje Cells of the cerebellum showing the highest expression of any neuron type examined. Subsequent conditional Gnal knockout in Purkinje cells led to markedly decreased intracellular cAMP levels and downstream cAMP-dependent enzyme activation. Our work provides a detailed characterization of Gnal expression throughout the brain and the biochemical consequences of loss of Gα olf signaling in vivo in neurons that highly express Gnal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The first tooth to erupt is the first mandibular molar, which is the tooth with the highest number of retreatments. Several factors are responsible for the failure of the endodontic success and one of the most important being the particular pulp anatomy of each tooth. To aim was determine the prevalence of the middle mesial (MM) canal in first mandibular molars and to study if there are predisposing factors to the presence of this canal by retrospectively analyzing cone-beam computed tomography (CBCT) images in vivo., Material and Methods: CBCT images of 100 patients were selected. A total of 206 first mandibular molars were examined. The CBCTs were analysed using Careastream CS 3D imaging software. Findings of MM canals were recorded along the variables sex and left/right side. Prevalence was compared using the Chi-square test ( P < 0.05) and Cramer's V was used to indicate the effect size between the variables., Results: Of the 206 teeth analysed, the prevalence of MM canals was 33.11% (49 teeth). There was no statistically significant difference between sex and prevalence of the MM canal. There was a significant difference between sex and the distance between the mesial canals was found, being the most common range in women was 1-2 mm (35.8%) and 2-3 mm (51%) in men. The most common range of distance between the mesial canals where the MM canal was localized was 3-4 mm (50%), being statistically significant ( p <0,05)., Conclusions: This cross-sectional study showed a high prevalence of MM canals (33.11%) in first mandibular molars. The prevalence of the MM canal was significantly higher when the distance between mesiobucal and mesiolingual canals was 3-4mm. This knowledge let direct the clinicians in locating MM canal for improving endodontic prognosis. Key words: Cone-beam computed tomography, middle mesial canal, prevalence., Competing Interests: The authors declare that they have no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not- for- profit sectors., (Copyright: © 2024 Medicina Oral S.L.)

Loss-of-function mutations in GNAL have been linked to an adult-onset, isolated dystonia that is largely indistinguishable from idiopathic dystonia. GNAL encodes Gα olf , a heterotrimeric G-protein α subunit with a defined molecular function to increase the production of the second messenger cAMP. Gα olf is abundant in the striatum, and is the only stimulatory G-protein in many cell types of the striatum. Due to the defined molecular signaling pathway and expression pattern of Gα olf , the clear genetic link to dystonia makes GNAL an exciting target to understand the pathological mechanisms of not only this genetic dystonia, but also the larger idiopathic disease. To better understand GNAL -linked dystonia, we generated a novel genetic mouse model that allows us to conditionally knock out Gnal in a site and time-specific manner. In the current study we used genetic or AAV based approaches to express Cre to knockout striatal Gnal in our novel Gnal fl/fl model. We then performed motor behavioral testing and ex vivo whole-cell patch clamp electrophysiology of striatal spiny projection neurons to interrogate how loss of Gnal leads to dystonia. Mice with conditional striatal knockout of Gnal show hindlimb clasping, other dystonia-like postures, less motor coordination, slowness, and torticollis as compared to age-matched controls. Furthermore, striatal spiny projection neurons show increased excitability in Gnal knockout animals. These exciting data are the first to report uninduced, overt dystonia in a mouse model of GNAL- linked dystonia, and directly correlate these with changes in spiny projection neuron electrophysiological properties. Our results show that adult loss of Gnal in the striatum leads to the development of dystonia, through homeostatic, paradoxical increases in spiny projection neuron excitability, and suggest that therapeutic strategies aimed at decreasing this hyperexcitable phenotype may provide symptomatic relief for patients with disease. One Sentence Summary: When Gnal is knocked out in the striatum of mice we observe overt behavioral symptoms and hyperexcitability in striatal spiny projection neurons.

Aim: To investigate the outcome of elective full pulpotomy, using calcium silicate-based cements (CSBC), after 2 years, in symptomatic mature permanent teeth with carious lesions, diagnosed as irreversible pulpitis, and analyse the capacity of Wolters et al. (2017) classification to predict the likelihood of treatment failure., Methods: The treatment records of 56 patients with symptomatic mature teeth with carious lesions, diagnosed as irreversible pulpitis and treated by elective full pulpotomy, using CSBCs as pulp capping materials, were reviewed. Thirteen teeth were excluded. The remaining 43 teeth were evaluated retrospectively at 24 months. Fisher`s exact test with the Lancaster's mid-P adjustment was used to assess different outcomes amongst the diagnostic categories., Results: Four of the cases failed before 24 months and required root canal treatment (RCT). Overall success rate at 2 years was 90.7% (39 of 43). An inverse, but non-significant, correlation was observed between the severity of pulpitis according to the Wolters classification and the treatment success rate (p > 0.05). The type of CSBC used was associated to the success rate (OR = 10.5; 95% C.I. = 0.5 - 207.4; p = 0.027), being 82% with Endosequence and 100% with Biodentine. Postoperative pain associated significantly to lower success rate (66.7%) (Odds ratio = 8.0; 95% C.I. = 0.7 - 95.9; p = 0.047)., Conclusions: Elective full pulpotomy using a CSBC was a successful choice for the treatment of mature permanent teeth with symptoms indicative of irreversible pulpitis. There were no significant differences between the success rate of mild, moderate and severe pulpitis. Postoperative pain could be considered a risk marker for failure of full pulpotomy. The term "irreversible pulpitis" should be re-signified to indicate the need for access to the pulp chamber, rather than an indication for extraction or RCT., (© 2024. The Author(s).)

Background: The present study aimed to evaluate nutritional intake among a group of male patients in the dental clinic with and without periodontal disease to search for associations between nutritional profile and periodontal health., Methods: To this purpose, nutritional intake of macronutrients, fiber, vitamins, and minerals were compared evaluating both clinical parameters and periodontal status. Non periodontitis patients were compared with stage III and IV periodontitis and its extension according to the 2017 classification., Results: After multivariate analysis, statistically significant associations were found between the dietary intake of energy, total fat, cholesterol, calcium, saturated fat, monounsaturated fat and folic acid and iodine and periodontitis status. This study reports an inverse association between cholesterol and iodine and periodontitis and a direct association with saturated fat, monounsaturated fat, and folic acid., Conclusions: Maintaining an adequate intake of fat, iodine, calcium, and cholesterol and avoiding an excessive intake of energy, saturated fat, monounsaturated fat, and folic acid could be important to controlling periodontitis., (© 2024. The Author(s).)

Background: The prevalence of depression and anxiety has increased in recent years, with many individuals having trouble accessing mental health support. Smartphones have become an integral part of modern life, with apps offering new ways to deliver evidence-based self-help strategies to cope with common mental health symptoms. However, most of them do not have empirical evidence of their overall effectiveness or the effectiveness of their components, which could pose a risk for users., Objective: The aim of this study is to evaluate the effectiveness of the modules of evaluation, psychoeducation, and emotional regulation strategies in a multiplatform self-help mental health mobile app in the Maule region of Chile., Methods: A sample of 196 adults will be selected, who will be randomly assigned to different components of the app for a fixed period to assess its ability to reduce symptomatology., Results: The trial is not yet recruiting and is expected to end in October 2024. The first results are expected in April 2024., Conclusions: This is the first study in Chile to develop and test the effectiveness of a mobile app to manage anxiety and depression symptoms in adults. The intervention proposed is based on evidence suggesting that the internet or remote intervention tools and self-management of prevalent symptomatology could be the future of mental health care systems in the digital era. If the effects of the intervention are positive, wide implementation in Chile and other Spanish-speaking countries could be possible in the future., International Registered Report Identifier (irrid): PRR1-10.2196/52324., (©Nadia Ramos, Felipe Besoain, Natalia Cancino, Ismael Gallardo, Paula Albornoz, Andres Fresno, Rosario Spencer, Soledad Schott, Daniel Núñez, Carolina Salgado, Susana Campos. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.03.2024.)

Prostate cancer is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of PSMA imaging with PET/CT over conventional imaging for primary diagnoses. Single photon emission computed tomography is more available worldwide, and the imaging agent is low in cost. The aim of this study is to compare the diagnostic accuracy of 99m Tc-EDDA/HYNIC-iPSMA SPECT/CT to 18 F-PSMA-1007 PET/CT in the primary diagnosis of prostate cancer and the impact on clinical staging., Methods: In this prospective controlled study, 18 patients with histologically confirmed prostate cancer with unfavorable intermediate-, high-, and very high-risk characteristics were recruited to undergo 18 F-PSMA-PET/CT and 99m Tc-iPSMA SPECT/CT. The median age of the patients was 71 years old, and the median PSA level was 23.3 ng/mL. Lesions were divided into the prostate, seminal vesicles, lymph nodes, bone, and visceral metastases. Volumetric analysis was also performed between the two imaging modalities and correlated with PSA levels., Results: A total of 257 lesions were detected on 18 F-PSMA-PET/CT: prostate (n = 18), seminal vesicles (n = 12), locoregional lymph nodes (n = 62), non-locoregional (n = 67), bone (n = 90), and visceral (n = 8). Of these, 99m Tc-iPSMA-SPECT/CT detected 229 lesions, while both reviewers detected 100% of the lesions in the prostate (18/18), seminal vesicles (12/12), and visceral (8/8); LN LR (56/62; 90%), NLR (57/67; 85%), and bone (78/90; 86%). There were no statistically significant differences between volumetric parameters ( t = -0.02122; p = 0.491596)., Conclusions: 99m Tc-iPSMA SPECT/CT is useful in the primary diagnosis of prostate cancer. Despite it showing a slightly lower lesion detection rate compared to 18 F-PSMA PET/CT, it exhibited no impact on clinical staging and, consequently, the initial treatment intention.

Background: The indicated treatment in cases of apical periodontitis (AP), a disease very prevalent in diabetic patients, is root canal treatment (RCT). This study aims to conduct a systematic review with meta-analysis to answer the following PICO question: In adult patients, does the absence or presence of diabetes affect the prevalence of root filled teeth (RFT)"?, Material and Methods: PRISMA Guidelines have been followed to carry out this systematic review. A literature search was undertaken in PubMed-MEDLINE, Embase and Scielo. All studies reporting the prevalence of RFT in diabetic patients and control subjects using radiographic examination were included. Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed., Results: Five studies fulfilled the inclusion criteria. Prevalence of RFT were estimated with 701 people and 15,882 teeth. Among diabetic patients, 6.1% of teeth had undergone RCT, while in controls this percentage was 3% (OR = 1.7; 95% CI = 1.0 - 2.9; p = 0.065). Among diabetic patients, 65% had at least one RFT, while in controls this percentage dropped to 55% (OR = 1.4; 95% CI = 0.5 - 3.7; p > 0.05). The certainty of evidence was low., Conclusions: The prevalence of RFT in diabetic patients is almost double that in the control population, however this result is only marginally significant. Dentists must take into account the high prevalence of RFT in diabetic patients, investigating the presence of diabetes in those patients in whom a high frequency of RCT is observed. Key words: Diabetes, endodontics, epidemiology, root canal treatment, root filled teeth, prevalence, survey, population-based study., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest. This research received no specific grant from any funding agency., (Copyright: © 2023 Medicina Oral S.L.)

177 Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177 Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177 Lu-iPSMA and 177 Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177 Lu-iPSMA and 177 Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177 Lu-iPSMA (range 1-5 administrations; 394 treatment doses) or 177 Lu-DOTATOC (range 2-8 administrations; 511 treatment doses) at intervals of 1.5-2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10-7 to 3-1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177 Lu-iPSMA and 177 Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

Objective: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic and to find common risk factors., Methods: Male patients, older than 50 years, attended their first dental visit to the School of Dentistry for a period of two years, and it was proposed to evaluate undiagnosed type 2 diabetes mellitus. Periodontal, biochemical, microbiological examinations, nutritional profile, and physical activity were performed., Results: A total of 106 patients were examined, 6 (5.6%) had diabetes, and 37 (34.9%) had prediabetes without prior diagnosis. The severity of periodontitis was greater in patients with diabetes. Most of the patients were overweight and had increased systolic blood pressure. Patients with prediabetes and periodontitis had a low adherence to the Mediterranean diet. Tannerella forsythia was present in more patients with periodontitis, and the prevalence of Aggregatibacter actinomycetemcomitans is practically absent in groups with periodontitis, except for the group with diabetes., Conclusions: In the population studied, the prevalence of patients without a diagnosis of diabetes and prediabetes was very high and underestimated. The increased severity of periodontitis in patients with diabetes and in conjunction with the high level of cortisol seen in patients with periodontitis, especially those with diabetes, emphasize the dysregulation of the immunoinflammatory system., Clinical Significance: It is essential to add all this data to our dental practice to cover patient health with a broader landscape., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including "leaky gut" have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG 35-55 -induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1β and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of Akkermansiaceae family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease.

The ubiquity of mobile devices and access to the internet has changed our daily life and, in some cases, promoted and facilitated social and sexual interrelationships. There are many applications of technology and campaigns promoting healthy behaviors and prevention of sexually transmitted infections. Can we develop a strategy for the same purpose using mobile devices, based on the theory of attitude change? We developed an app and tested it with 105 undergraduate students, where they had to actively think in favor of condom use with a high amount of elaboration, leading to attitudes and behavioral intention (BI) in concordance with contemporary theories about attitudes and behavioral change. PROCESS macro models were used to analyze potential mediations. Results show a significant correlation between thoughts and attitudes, and attitudes partially mediated the association between thoughts and condom use. Individuals with positive thoughts tended to positively correlate their thoughts with their attitudes, and, consequently, these attitudes with their BI. In this study, we showed that (1) it was possible to develop and test an app based on the elaboration likelihood model (ELM); (2) consistent with previous studies, attitudes partially mediated the association between thoughts and condom use (BI) in a mobile environment; and (3) applications of this strategy can be used to build new approaches for prevention in health care.

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18 F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18 F PSMA-1007, 18 F AlF-NOTA-Octreotide, and 18 F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18 F-FDG PET/CT, 174 lesions by 18 F PSMA-1007, and 59 by 18 F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18 F-FDG PET/CT and 18 F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18 F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18 F PSMA-1007 detected more bone lesions. 18 F AlF-NOTA-Octreotide showed no significant utility.

Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which 131 I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of 123 I or 124 I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes., Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic 131 I dose whole body scan (WBS) and complementary SPECT/CT, as well as 68 Ga-PSMA-11 PET/CT., Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. 68 Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas 131 I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 - 0.91), as opposed to 131 I (κ = 0.86; 95% CI, 0.71 - 0.76)., Conclusions: 68 Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to 131 I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents., Competing Interests: The 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 © 2021 Pitalua-Cortes, García-Perez, Vargas-Ahumada, Gonzalez-Rueda, Gomez-Argumosa, Ignacio-Alvarez, Soldevilla-Gallardo and Torres-Agredo.)