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1.
Article in English | MEDLINE | ID: mdl-38762160

ABSTRACT

Cannabidiol (CBD) is a phytocannabinoid devoid of psychostimulant properties and is currently under investigation as a potential antidepressant drug. However, the mechanisms underlying CBD's antidepressant effects are not yet well understood. CBD targets include a variety of receptors, enzymes, and transporters, with different binding-affinities. Neurochemical and pharmacological evidence indicates that both serotonin and BDNF-TrkB signalling in the prefrontal cortex are necessary for the antidepressant effects induced by CBD in animal models. Herein, we reviewed the current literature to dissect if these are independent mechanisms or if CBD-induced modulation of the serotonergic neurotransmission could mediate its neuroplastic effects through subsequent regulation of BDNF-TrkB signalling, thus culminating in rapid neuroplastic changes. It is hypothesized that: a) CBD interaction with serotonin receptors on neurons of the dorsal raphe nuclei and the resulting disinhibition of serotonergic neurons would promote rapid serotonin release in the PFC and hence its neuroplastic and antidepressant effects; b) CBD facilitates BDNF-TRKB signalling, especially in the PFC, which rapidly triggers neurochemical and neuroplastic effects. These hypotheses are discussed with perspectives for new drug development and clinical applications.


Subject(s)
Antidepressive Agents , Brain-Derived Neurotrophic Factor , Cannabidiol , Receptor, trkB , Serotonin , Signal Transduction , Cannabidiol/pharmacology , Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Serotonin/metabolism , Animals , Humans , Signal Transduction/drug effects , Receptor, trkB/metabolism
2.
BMJ Open Sport Exerc Med ; 10(2): e002029, 2024.
Article in English | MEDLINE | ID: mdl-38808265

ABSTRACT

People with Parkinson's disease (PD) face disruptions in arm swing (AS) motion during walking, including a reduction in amplitude and an increase in asymmetry. Both conditions are detrimental to gait performance. Nordic walking (NW) is a walking modality that uses poles and can positively affect the parameters of AS. This study aims to compare an NW with a free walking (FW) protocol and investigate its effects on AS asymmetry, AS amplitude and gait parameters in people with PD. Twenty-eight people with PD, stages 1-3 on the Hoehn and Yahr Scale, will be randomly assigned to the NW training group (n=14) or the FW training group (n=14). The primary outcomes are amplitude asymmetry of AS (%) and AS amplitude (deg). We will also analyse temporospatial measurements during walking, functional mobility and quality of life. Blinded researchers will conduct evaluations at baseline (T0), postintervention (T1) and at 1 month follow-up (T2). Participants will complete 24 supervised NW or FW training sessions for 12 weeks. This is the first study to address the effects of NW on the asymmetry of AS, AS amplitude and its influence on gait parameters. We hypothesise that an NW programme in PD will reduce the asymmetry and increase the AS amplitude during gait to a greater extent than FW. The results of this study may provide new evidence to understand the effects of NW on gait in people with PD. The study was registered in ClinicalTrial.gov (NCT06342271).

3.
Neurotherapeutics ; 21(3): e00364, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38669936

ABSTRACT

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recovery. In parallel, the advent of incisionless treatment with focused ultrasound ablation (FUSA) can offer patients life-changing symptomatic relief. Recent research has underscored the potential to further optimize DBS and FUSA outcomes by conceptualizing the therapeutic targets as critical nodes embedded within specific brain networks instead of strictly anatomical structures. This paradigm shift was facilitated by integrating two imaging modalities used regularly in brain connectomics research: diffusion MRI (dMRI) and functional MRI (fMRI). These advanced imaging techniques have helped optimize the targeting and programming techniques of surgical neuromodulation, all while holding immense promise for investigations into treating other neurological and psychiatric conditions. This review aims to provide a fundamental background of advanced imaging for clinicians and scientists, exploring the synergy between current and future approaches to neuromodulation as they relate to dMRI and fMRI capabilities. Focused research in this area is required to optimize existing, functional neurosurgical treatments while serving to build an investigative infrastructure to unlock novel targets to alleviate the burden of other neurological and psychiatric disorders.


Subject(s)
Deep Brain Stimulation , Magnetic Resonance Imaging , Humans , Deep Brain Stimulation/methods , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/trends , Brain/diagnostic imaging , Brain/physiology , Neurosurgical Procedures/methods
4.
Eur J Int Relat ; 30(1): 52-77, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38425475

ABSTRACT

Whose preferences influence the design of international institutions? Scholarship on the legalization of international politics and creation of international legal institutions largely adopts a state-centric perspective. Existing accounts, however, fail to recognize how states often delegate authority over institutional design tasks to independent legal experts whose preferences may diverge from those of states. We develop a principal-agent (PA) framework for theorizing relations between states (collective principals) and legal actors (agents) in the design process, and for explaining how legal actors influence the design of international institutions. The legal dimensions of the PA relationship increase the likelihood of preference divergence between the collective principal and the agent, but also create conditions that enable the agent to opportunistically advance its own design preferences. We argue that the more information on states' preferences the agent has, the more effectively it can exploit its legal expertise to strategically select and justify design choices that maximize its own preferences and the likelihood of states' acceptance. Our analysis of two cases of delegated institutional design concerning international criminal law at the United Nations and the African Union supports our theoretical expectations. Extensive archival and interview data elucidate how agents' variable information on states' preferences affects their ability to effectively advance their design preferences. Our theory reveals how independent legal experts with delegated authority over design tasks influence institutional design processes and outcomes, which has practical and normative implications for the legalization of international politics.

5.
World Neurosurg ; 185: 310-313, 2024 05.
Article in English | MEDLINE | ID: mdl-38395351

ABSTRACT

BACKGROUND: Neurosurgery is a specialty that has been dominated by males. Although there has been an increase in the number of women in the field, it is not yet close to being equal. Some noteworthy women who have carved the path for other women to follow in their footsteps include Drs. Sofía Ionescu and Diana Beck, the first and second female neurosurgeons worldwide, respectively. However, there are limited publications on Dr. María Cristina García-Sancho, the first Latina neurosurgeon. METHODS: The purpose of this review was to illuminate the neurosurgical community on the life of Dr. García-Sancho. A thorough literature was performed on medical and non-medical publications that were either authored by Dr. García-Sancho or mentioned her directly. RESULTS: Dr. García-Sancho earned her medical degree at the School of Medicine of the National Autonomous University of Mexico under the guidance of Dr. Clemente Robles, who founded Mexico's first neurosurgical department. Her training took her worldwide. CONCLUSIONS: Her expertise allowed her to pioneer a revolutionary advancement known as the one-step bilateral cordotomy. Her perseverance led her to becoming the head of the Department of Neurosurgery at the National Cancer Institute of Mexico and co-found the Mexican Society of Neurological Surgery, where she served on the board of directors. This review aims to advocate for an equitable environment in the field of neurosurgery with Dr. García-Sancho's story.


Subject(s)
Neurosurgeons , Neurosurgery , Neurosurgery/history , Neurosurgeons/history , History, 20th Century , Humans , Mexico , Physicians, Women/history , Female
6.
Neuropharmacology ; 248: 109870, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38401791

ABSTRACT

Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.


Subject(s)
Cannabidiol , Depression , Rats , Male , Animals , Depression/drug therapy , Depression/genetics , Cannabidiol/pharmacology , Endocannabinoids/metabolism , Synaptophysin/metabolism , Antidepressive Agents/pharmacology , Prefrontal Cortex , Neuronal Plasticity , Disease Models, Animal
7.
Eur Arch Otorhinolaryngol ; 281(6): 2793-2805, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38189964

ABSTRACT

PURPOSE: Radiotherapy is one of the main strategies used in the treatment of cancer patients and it can cause early or late xerostomia and/or hyposalivation. Therapeutic management of xerostomia includes oral hygiene, sialogenic agents among others. METHODS: This study reviews the use of extra-oral salivary glands photobiomodulation in treating xerostomia and/or hyposalivation after radiotherapy and performs a meta-analysis of this data. RESULTS: After a broad search of the literature, eight clinical studies were selected. DISCUSSION: In a safe way, the studies found that extra-oral stimulation of the salivary glands has benefits in the hyposalivation and changes in salivary flow resulting from lesions by radiotherapy. A meta-analysis found significant values in pain comparing the pre- and post-treatment moments (MD - 3.02, I2 95%, IC - 5.56; - 0.48) and for stimulated salivary flow at 30 days after the end of radiotherapy (MD 2.90, I2 95%, IC 1.96; 3.84). CONCLUSION: The most promising parameters comprise wavelengths between 630 and 830 nm, radiant exposure from 2 to 10 J/cm2, two-to-three times a week, before the radiotherapy damage, and homogeneously in the glands. Therefore, Light-Emitting Diode (LED) stimulation of larger areas than the punctual stimulation of small millimeters of the Low-Level Laser Therapy (LLLT) appears to be promising.


Subject(s)
Low-Level Light Therapy , Salivary Glands , Xerostomia , Humans , Low-Level Light Therapy/methods , Xerostomia/etiology , Salivary Glands/radiation effects
8.
J Neurol Surg B Skull Base ; 85(1): 44-56, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38274488

ABSTRACT

Objective The North American Skull Base Society (NASBS) multidisciplinary annual conference hosts skull base researchers from across the globe. We hypothesized that the work presented at the NASBS annual conference would reveal diverse authorship teams in terms of specialty and geography. Methods In this retrospective review, abstracts presented at the NASBS annual meeting and subsequently published in the Journal of Neurological Surgery Part B: Skull Base between 01/01/2011 and 12/31/2020 were collected. Variables extracted included year, type of presentation, and author names and affiliations. Statistical analyses were performed with SPSS V23.0 with p -values less than 0.05 considered significant. Geographic heat maps were created to assess author distribution, and a network analysis was performed to display authorship collaboration between geographic regions. Results Of 3,312 published abstracts, 731 (22.1%) had an author with an affiliation outside of the United States. Fifty-seven distinct countries were represented. Three-hundred twenty-four abstracts (9.8%) had authorship teams representing at least 2 different countries. The top five US states by abstract representation were Pennsylvania, California, New York, Ohio, and Minnesota. A majority of authors reported neurosurgery affiliations (56.7% first authors, 53.2% last authors), closely followed by otolaryngology (39.1% first authors, 41.5% last authors). No solo authors and very few (3.3%) of the first authors reported a departmental affiliation outside of otolaryngology or neurosurgery. Conclusions Authors from many countries disseminate their work through poster and oral presentations at the NASBS annual meeting. Ten percent of abstracts were the product of international collaboration. Most authors were affiliated with a neurosurgery or otolaryngology department.

9.
J Neurol Surg B Skull Base ; 85(1): 57-66, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38274485

ABSTRACT

Objective The North American Skull Base Society (NASBS) annual conference brings together skull base researchers from surgical and nonsurgical fields. Our objective was to quantify the contributions of the authors by gender, who presented their work at NASBS and were subsequently published in the Journal of Neurological Surgery Part B: Skull Base . Methods Oral and poster abstracts presented at the NASBS annual meeting from January 1, 2011 to December 31, 2020 were extracted from the Journal of Neurological Surgery Part B: Skull Base. The genderize.io Web application programming interface was utilized to determine authorship gender. A minority of first and last authors had departmental affiliations listed; a subgroup analysis was performed of these authors. Results Female gender was assigned to 498 (17.8%) of the 2,798 first authors and 269 (9.7%) of the 2,762 last authors. Female authorship has consistently increased over the last decade. Representation was higher in otolaryngology (23.3% of first authors, 12.1% of last authors; p = 0.018) than neurosurgery (13.5% of first authors, 4.3% of last authors; p = 0.004). Female researchers were not less likely than their male counterparts to receive prestigious oral presentations. Of the 52 total countries represented, 20 (38.5%) had at least one female first author. Representation varied dramatically between countries. Conclusion The NASBS' efforts have undoubtedly contributed to these impressive strides toward gender parity. More work is needed to ensure that the best and the brightest, regardless of background, continue to contribute to skull base surgery research.

10.
J Neurosurg ; 140(2): 552-559, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37548567

ABSTRACT

OBJECTIVE: Severe traumatic brain injury (TBI) is a public health issue posing significant morbidity and mortality to afflicted patients. While the effect of time to surgery as the primary factor for survival has been extensively studied, long-term dispositional outcomes following intracranial hemorrhage evacuation have not been well described in the literature. Therefore, the aim of this study was to elicit potential prognostic factors in patients presenting with severe TBI that may have a significant impact on discharge disposition. METHODS: The authors searched the National Trauma Data Bank (NTDB) for patients included between 2010 and 2019, solely focusing on those with a Glasgow Coma Scale score ≤ 8, signifying severe TBI, and with associated intracranial hemorrhage treated via surgical intervention. Numerous characteristics were analyzed, including demographics (age, sex, race, ethnicity, payment status), discharge disposition, time to surgery, pupillary response, midline shift (> 5 mm), and postoperative inpatient complications and comorbidities. Disposition included routine discharge to home, discharge to home with home health services (HHSs), discharge to acute inpatient rehabilitation (AIR), discharge to a skilled nursing facility (SNF)/long-term acute care hospital (LTACH), and death. RESULTS: The authors analyzed data on 7308 patients, 69.6% of whom were White and 11.2% of whom were Black. More young Black and Hispanic patients had severe TBI events than their matched elders, whereas more elderly White patients had severe TBI events than their matched younger counterparts. The most common disposition across all ages was SNF/LTACH. Septuagenarians and octogenarians were 12.1 and 21 times more likely, respectively, to die following a severe TBI than their younger counterparts (p < 0.001). Patients aged 18-29 were 1.7 times more likely to be discharged with HHSs (p < 0.001). Minority race/ethnicity groups were less likely to be discharged to AIR. As age increased, a patient's intensive care unit stay increased by 15 days (p < 0.001) and total hospital length of stay increased by 25 days (p < 0.001). CONCLUSIONS: Neurosurgical evacuation of intracranial hemorrhage in severe TBI has variable long-term morbidity. Utilizing the largest collection of trauma data within the United States, the authors present quantitative evidence on discharge disposition. Understanding these tangible points can help neurosurgeons present potential outcomes to patients, promote preventative care, and generate tangible conversations with patients and their family members.


Subject(s)
Brain Injuries, Traumatic , Brain Injuries , Aged , Aged, 80 and over , Humans , United States , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/surgery , Hemorrhage , Patient Discharge , Postoperative Complications , Intracranial Hemorrhages , Retrospective Studies
11.
Front Glob Womens Health ; 4: 1267156, 2023.
Article in English | MEDLINE | ID: mdl-38074279

ABSTRACT

Introduction: Immigration has increased significantly in Chile. Despite that all pregnant women, regardless of nationality and immigration status, have the right to access to all healthcare services during pregnancy, childbirth, and postpartum, inequities in health care outcomes and health provision have been reported. During COVID-19 pandemic, these inequities are completely unknown. Objective: The aim of this study was to compare the incidence of c-sections according to mother's migration status, as well as other maternal care and perinatal outcomes in women giving birth at San José Hospital in Santiago, Chile, during the COVID-19 pandemic. Methods: A retrospective cohort study was designed including 10,166 registered single births at the San José Hospital between March 2020 and August 2021. To compare between groups, statistical tests such as Chi-square and Fisher's exact were used. Log Binomial regression models were performed adjusted for potential confounding variables. To estimate the strength of association the relative risk was used. Results: Immigrant mothers account for 48.1% of the registered births. Compared to non-immigrant women, immigrants exhibit a higher proportion of c-section, specifically, emergency c-section (28.64% vs. 21.10%; p-value < 0.001) but a lower proportion of and having a preterm birth (8.24% vs. 13.45%; p < 0.05), receiving personalized childbirth care (13.02% vs. 14.60%; p-value < 0.05), companion during labor and childbirth (77.1% vs. 86.95%; p-value < 0.001), And postpartum attachment to newborn (73% vs. 79.50%; p-value < 0.001). The proportion of COVID exposure was not significant between groups, not the severity also. Haitians had a highest risk of undergoing emergency c-section (aRR = 1.61) and Venezuelans had a highest risk of elective c-section (aRR = 2.18) compared to non-immigrants. Conclusion: This study reports high rates of c-sections in the entire population, but in immigrant populations it is even higher. Additionally, it found gaps in maternal care and perinatal outcomes between immigrants and non-immigrants. More studies are needed to elucidate the possible causes of these differences and establish new regulations to protect the reproductive rights of the immigrant population.

12.
BMJ Open Sport Exerc Med ; 9(4): e001749, 2023.
Article in English | MEDLINE | ID: mdl-37920278

ABSTRACT

Physical inactivity is a major health concern, associated with the development of several non-communicable diseases and with an increased mortality rate. Therefore, promoting active lifestyles has become a crucial public health necessity for enhancing overall health and quality of life. The WHO guidelines for physical activity (PA) present valuable contributions in this respect; however, we believe that greater specificity should be added or complemented towards physical exercise (PE) testing, prescription and programming in future recommendations. In this review article, we suggest simple and practical tools accessible to the entire population to improve the specificity of this approach, highlighting aspects of PE programming used by trained subjects. By adopting these suggestions, exercise professionals, clinicians and physical trainers can optimise the current general PA recommendations towards PE prescription to improve fitness status and encourage PE adherence in the general population.

13.
Einstein (Sao Paulo) ; 21: eRC0356, 2023.
Article in English | MEDLINE | ID: mdl-37729311

ABSTRACT

Despite its rarity, symptomatic micronutrient deficiency remains a public health problem. Scurvy is the differential diagnosis for bleeding disorders and hematological and rheumatological diseases, especially in patients with eating disorders. However, it is unrelated to autism spectrum disorders or other neurodevelopmental disorders. A previously healthy 10-year-old boy living in São Paulo, Brazil, had a history of significant food selectivity unrelated to autism spectrum disorder, resulting in symptomatic ascorbic acid deficiency (scurvy). This resulted in pain and purpuric lesions on the lower limbs, gingival edema, bleeding during tooth brushing, asthenia, weakness, malaise, and sadness. Therefore, dietary anamnesis is important for routine monitoring of child growth and development. This process helps prevent nutritional deficiencies, facilitates early diagnosis of eating disorders, and enables multidisciplinary follow-up for these patients.


Subject(s)
Autism Spectrum Disorder , Malnutrition , Scurvy , Male , Child , Humans , Scurvy/complications , Scurvy/diagnosis , Brazil , Diagnosis, Differential
14.
Hisp Health Care Int ; : 15404153231187394, 2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37455338

ABSTRACT

The present longitudinal study examined changes in perceived access to health care among a recently immigrated cohort of Latina young adults who were assessed annually during their first 3 years in the United States. A parallel process growth model of perceived access to health care and neighborhood collective efficacy was examined, accounting for socioeconomic indicators and immigration status. Five hundred thirty Latina young adults (ages 18-23) participated at baseline assessment, and approximately 95% were retained over three annual assessment time points. Participants' mean level of perceived access to health care increased during their initial 3 years in the United States. Women who reported more of an increase in perceived access to health care tended to also indicate increased neighborhood collective efficacy relative to their peers during their first 3 years in the United States. Findings offer important information about the individual- and community-level factors that influence recently immigrated Latinas' health care access.

15.
Behav Pharmacol ; 34(4): 213-224, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37171460

ABSTRACT

Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01-3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15-60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.


Subject(s)
Anti-Anxiety Agents , Antipsychotic Agents , Cannabidiol , Cannabinoids , Mice , Male , Animals , Cannabidiol/pharmacology , Antipsychotic Agents/pharmacology , Anti-Anxiety Agents/pharmacology , Catalepsy/chemically induced , Antidepressive Agents/pharmacology , Amphetamine , Dronabinol/pharmacology
16.
Int J Neuropsychopharmacol ; 26(5): 350-358, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37067203

ABSTRACT

BACKGROUND: Recent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine's antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach. METHODS: We evaluated the behavioral sensitivity to 20 mg/kg S-ketamine (i.p.) in male and female Flinders Sensitive Line rats (FSLs) and their counterpart Flinders Resistant Line rats (FRLs) subjected to the open field and forced swim tests. Female rats were disaggregated into different estrous phases, and the behavioral outcomes were compared. RESULTS: Acute administration of S-ketamine had robust antidepressant-like effects in FSLs. Within our study power, we could not detect sex- or estrous cycle-specific different antidepressant-like responses to S-ketamine in FSLs. Fluctuations in the levels of ovarian sex hormones across different estrous cycles did not behaviorally affect S-ketamine's rapid-acting antidepressant mode of action. No sex-related or estrous cycle-related impact on behavioral despair was observed even among FRLs and saline-treated FSLs. CONCLUSIONS: We conclude that physiological oscillations of estrogen and progesterone levels neither amplify nor diminish the behavioral antidepressant-like effect of S-ketamine. In addition, fluctuations of ovarian sex hormones do not predispose female animals to exhibit enhanced or reduced depressive-like and anxiety-like behaviors.


Subject(s)
Depression , Ketamine , Rats , Male , Female , Animals , Depression/drug therapy , Antidepressive Agents/pharmacology , Ketamine/pharmacology , Estrous Cycle
17.
Int J Pharm ; 633: 122612, 2023 Feb 25.
Article in English | MEDLINE | ID: mdl-36642349

ABSTRACT

This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co-delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO-based nanodispersions were obtained using Kolliphor® P407 (KP) and/or sodium cholate (CH), and characterized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition-dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05-0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solution, and a further reduction (1.5-fold) was observed by MB photoactivation.


Subject(s)
Metformin , Methylene Blue , Administration, Cutaneous , Methylene Blue/pharmacology , Skin , Humans , Cell Line, Tumor
18.
Childs Nerv Syst ; 39(6): 1485-1493, 2023 06.
Article in English | MEDLINE | ID: mdl-36454311

ABSTRACT

PURPOSE: Low-grade gliomas compose 30% of pediatric central nervous system tumors and outcomes of disease-free progression, and survival is directly correlated to the extent of resection. The use of sodium fluorescein (Na-Fl) is an intraoperative method in the localization of tumor cells in adult patients to optimize resection. Our purpose is to describe the use of Na-Fl in pediatric low-grade gliomas and its outcomes. METHODS: Patients under 18 years of age with low-grade gliomas at the author's institution underwent resection with the use of Na-Fl, with review of preoperative imaging findings, intraoperative results, and follow-up. Then, a comprehensive, narrative literature review of the use of Na-Fl in pediatric low-grade glioma was performed. RESULTS: Our single-institution use of Na-Fl in pediatric patients with suspected low-grade glioma demonstrated excellent results of intraoperative enhancement of tumor cells as well as gross total resection. The literature demonstrated 84% Na-Fl staining and 59.2% of gross total resection in pediatric low-grade gliomas with few small case studies, a range of reported findings, and few side effects. CONCLUSION: Na-Fl has a promising use in low-grade glioma resection in the pediatric patient population. Further research is warranted, such as randomized controlled studies, to assess Na-Fl as a potential tool in improving resection and long-term favorable outcomes.


Subject(s)
Brain Neoplasms , Glioma , Adult , Humans , Child , Adolescent , Fluorescein , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Glioma/diagnostic imaging , Glioma/surgery , Glioma/pathology , Neurosurgical Procedures/methods
19.
RGO (Porto Alegre) ; 71: e20230048, 2023. tab, graf
Article in English | LILACS-Express | LILACS, BBO - Dentistry | ID: biblio-1514652

ABSTRACT

ABSTRACT Osseointegrable dental implants are biomaterials made of titanium or other alloys mixed with titanium, which have high biocompatibility and allow osseointegration. However, this process can be modulated by changes in the complex mechanisms between microbiota, immune response and host. The present study aims to present how the immune system-microbiota-host interaction influences the osseointegration process of titanium dental implants and its alloys. A literature review was performed through electronic and manual searches in several databases, including PubMed, LILACS, Google Scholar, SciELO and Web of Science for articles published in the last 20 years in English and Portuguese. The formation of a temporary fibrin matrix on the implants surface after implantation implies the recruitment, adhesion and activity of immune cells at this site, with the release of pro-inflammatory molecules and recruitment of neutrophils. In the second moment, monocytes and macrophages (M1) are recruited, producing, in this step, reactive oxygen species. In the later stage of inflammation, macrophages (M2) help in tissue regeneration with expression of anti-inflammatory cytokines. In addition, the implants surface provides a site for microbial colonization mediated by salivary pellicle and topographical features. Thus, in symbiosis the modulation of the immune response will be favorable to osseointegration. However, the dysbiotic process exacerbates the inflammatory progression modulating the immune response influencing abnormal tissue healing or scar and fibrosis formation, compromising osseointegration. Different conditions of the subgingival microbiota will influence different immunological cascades, generating different cellular responses and positive or negative modulation of the osseointegration process.


RESUMO Os implantes dentários osseointegráveis são biomateriais constituídos de titânio ou outras ligas misturadas com titânio, as quais possuem alta biocompatibilidade e permitem a osseointegração. Esse processo pode ser modulado por alterações nos mecanismos complexos entre microbiota, resposta-imune e hospedeiro. O presente estudo busca apresentar como a interação sistema imune-microbiota-hospedeiro influenciam no processo de osseointegração proveniente de implantes dentários de titânio. Foi realizada uma revisão de literatura através de busca eletrônica e manual em diversas bases de dados, incluindo PubMed, LILACS, Google Acadêmico, SciELO e Web of Science para artigos publicados nos últimos 20 anos em inglês e português. A formação de uma matriz provisória de fibrina na superfície dos implantes após a implantação implica no recrutamento, adesão e atividade das células imunes, com a liberação de moléculas pró-inflamatórias e recrutamento de neutrófilos. No segundo momento, monócitos e macrófagos (M1) são recrutados, produzindo espécies reativas a oxigênio. Já no estágio posterior da inflamação, macrófagos (M2) ajudam na regeneração do tecido com expressão de citocinas anti-inflamatórias. Além disso, a superfície dos implantes oferece um local para colonização microbiana mediada pela película salivar e características topográficas. Assim, em simbiose a modulação da resposta imune vai ser favorável à osseointegração. Contudo, em estado de doença periodontal, o processo disbiótico exacerba a progressão inflamatória modulando a resposta imune influindo em um processo cicatricial comprometendo a osseointegração. Diferentes condições da microbiota subgengival vão influenciar em cascatas imunológicas diferentes gerando respostas celulares diferentes e modulação positiva ou negativa do processo de osseointegração.

20.
Einstein (Säo Paulo) ; 21: eRC0356, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1506179

ABSTRACT

ABSTRACT Despite its rarity, symptomatic micronutrient deficiency remains a public health problem. Scurvy is the differential diagnosis for bleeding disorders and hematological and rheumatological diseases, especially in patients with eating disorders. However, it is unrelated to autism spectrum disorders or other neurodevelopmental disorders. A previously healthy 10-year-old boy living in São Paulo, Brazil, had a history of significant food selectivity unrelated to autism spectrum disorder, resulting in symptomatic ascorbic acid deficiency (scurvy). This resulted in pain and purpuric lesions on the lower limbs, gingival edema, bleeding during tooth brushing, asthenia, weakness, malaise, and sadness. Therefore, dietary anamnesis is important for routine monitoring of child growth and development. This process helps prevent nutritional deficiencies, facilitates early diagnosis of eating disorders, and enables multidisciplinary follow-up for these patients.

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