RESUMO
Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.
Assuntos
Ansiolíticos , Animais , Feminino , Masculino , Gravidez , Ratos , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ácido gama-Aminobutírico , Chumbo/toxicidade , Ratos Long-Evans , Taurina/farmacologia , Taurina/uso terapêuticoRESUMO
Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.
Assuntos
Ansiolíticos , Taurina , Animais , Ansiolíticos/farmacologia , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Feminino , Hipocampo , Chumbo/toxicidade , Gravidez , Ratos , Ratos Long-Evans , Taurina/farmacologiaRESUMO
Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb2+-exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60-90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb2+-exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb2+-exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb2+-exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.
Assuntos
Atenção , Função Executiva , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Aprendizagem , Masculino , Fármacos Neuroprotetores/farmacologia , Gravidez , Ratos , Ratos Long-EvansRESUMO
Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb2+-exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb2+-exposure with no gender differences observed. However, Pb2+-exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Masculino , Projetos Piloto , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Ratos , Ratos Long-EvansRESUMO
PURPOSE: To investigate and to raise awareness about the influence of AI-powered software on the cognitive development of medical students, as well as the possible long-term ramifications. METHOD: This study combed through the literature on the use of AI in clinical settings and medical education, including chatbots powered by AI such as Chatgpt and Dale. The potential advantages and disadvantages of employing AI software for learning and complementing medical education, as well as its influence on critical thinking and problem-solving abilities, were assessed. RESULTS: no data analysis was performed. CONCLUSIONS: AI-powered software in medical education has potential benefits and drawbacks. While it can improve medical diagnosis and treatment and provide access to learning resources, the misuse of AI as a shortcut may hinder cognitive development and have long-term implications.
Assuntos
Disfunção Cognitiva , Estudantes de Medicina , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Cognição , Aprendizagem , Síndrome , Inteligência ArtificialRESUMO
The growing number of prevalent arteriovenous (AV) accesses has been associated with an increase in the incidence of procedures being performed to maintain patency. To reduce the rate of unnecessary procedures, the 2019 Kidney Disease Outcome Quality Initiative guidelines addended the AV access surveillance recommendations, which includes clinical monitoring and assessment of dialysis adequacy alone. Abnormal clinical findings would necessitate follow-up angiography with or without confirmatory duplex ultrasound. Due to poor patency, increased surveillance schedules have been proposed to identify stenosis early and potentially prevent acute thrombotic events and AV access failure. In this review, we outlined current AV access monitoring and maintenance procedure recommendations, as described by the Centers for Medicare and Medicaid Services and 2019 Kidney Disease Outcome Quality Initiative guidelines. In addition, we highlight the findings of recently published randomized controlled trials that have examined increased surveillance schedules.
Assuntos
Derivação Arteriovenosa Cirúrgica , Oclusão de Enxerto Vascular , Guias de Prática Clínica como Assunto , Diálise Renal , Grau de Desobstrução Vascular , Humanos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/normas , Diálise Renal/normas , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/terapia , Resultado do Tratamento , Guias de Prática Clínica como Assunto/normas , Fatores de Risco , Valor Preditivo dos Testes , Fatores de TempoRESUMO
This systematic review aimed to identify sex-specific outcomes in men and women after carotid endarterectomy (CEA) and carotid artery stenting (CAS), including transfemoral and transcarotid. A search of literature published from January 2000 through December 2022 was conducted using key terms attributed to carotid interventions on PubMed. Studies comparing outcome metrics post intervention (ie, myocardial infarction [MI], cerebral vascular accident [CVA] or stroke, and long-term mortality) among male and female patients were reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Overall, all studies reported low rates of perioperative complications. Among the studies that did not stratify outcomes by the preoperative symptom status, there were no significant sex differences in rates of perioperative strokes or MIs. Two studies, however, noted a higher rate of 30-day mortality in male patients undergoing CEA than in female patients. Analysis of asymptomatic patients undergoing CEA revealed no difference in perioperative MIs (female: 0% to 1.8% v male: 0.4% to 4.3%), similar rates of CVAs (female: 0.8% to 5% v male: 0.8% to 4.9%), and no significant differences in the long-term mortality outcomes. Alternatively, symptomatic patients undergoing CEA reported a higher rate of CVAs in female patients vs. male patients (7.7% v 6.2%) and showed a higher rate of death in female patients (1% v 0.7%). Among studies that did not stratify outcome by symptomatology, there was no difference in the 30-day outcomes between sexes for patients undergoing CAS. Asymptomatic patients undergoing CAS demonstrated similar incident rates across perioperative MIs (female: 0% to 5.9% v male: 0.28% to 3.3%), CVAs (female: 0.5% to 4.1% v male: 0.4% to 6.2%), and long-term mortality outcomes (female: 0% to 1.75% v male: 0.2% to 1.5%). Symptomatic patients undergoing CAS similarly reported higher incidences of perioperative MIs (female: 0.3% to 7.1% v male: 0% to 5.5%), CVAs (female: 0% to 9.9% v male: 0% to 7.6%), and long-term mortality outcomes (female: 0.6% to 7.1% v male: 0.5% to 8.2%). Sex-specific differences in outcomes after major vascular procedures are well recognized. Our review suggests that symptomatic female patients have a higher incidence of neurologic and cardiac events after carotid interventions, but that asymptomatic patients do not.
Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Resultado do Tratamento , Stents/efeitos adversos , Artérias Carótidas , Endarterectomia das Carótidas/efeitos adversos , Fatores de Risco , Medição de RiscoRESUMO
PURPOSE: To analyze the etiology and implications of optic disc swelling in cancer patients treated at a specialized tertiary cancer center in Jordan. METHODS: This was a retrospective study of all cancer patients who had optic disc swelling between January 2019 and December 2020 at King Hussein Cancer Center (KHCC). Patients' data included age, sex, laterality, visual acuity, and the underlying cause and management for the optic disc swelling. RESULTS: Optic disc swelling was present in 58 cancer patients (96 eyes), with 38 (65%) having bilateral involvement. Among these, 33 (57%) were female, and 43 (74%) were ≤40 years old. At diagnosis, 58 (63%) eyes had a best-corrected visual acuity (BCVA) better than 0.5, improving to 73 (76%) eyes at the last follow-up. High intracranial pressure (ICP) was the most common primary cause (30 patients/52%), followed by tumor infiltration of the optic nerve (10 patients/17%), optic nerve compression (7 patients/12%), and optic nerve inflammation (5 patients/9%). Four patients had pseudopapilledema. Among the 30 patients with high ICP, CNS tumors were predominant (21 patients/70%), with only 3 having idiopathic intracranial hypertension. Medications, including ATRA (All-Trans Retinoic Acid) and systemic steroids, contributed to increased ICP in six patients (20%). BCVA was less than 0.5 in all eyes (100%) affected by tumor infiltration, optic nerve inflammation, and ischemic optic neuropathy, while only eight eyes (14%) with optic disc swelling due to elevated ICP had a BCVA less than 0.5 (p < 0.0001). Management included steroids (53 patients/91%), acetazolamide (30 patients/52%), chemotherapy (20 patients/34%), radiation therapy (13 patients/22%), frequent lumbar punctures (12 patients/21%), and surgery (28 patients/48%). Visual acuity improved in 40 eyes (42%), with only 4 eyes (4%) experiencing deterioration. At a 12-month median follow-up period, 11 (19%) patients were dead, 10 (10%) eyes had poor vision (BCVA less than 0.1), and 21 (22%) eyes had BCVA 0.5 or better. CONCLUSIONS: Various underlying pathologies can induce optic disc swelling in cancer patients, a grave condition capable of causing vision loss. Notably, tumor infiltration of the optic nerve tends to result in more profound visual impairment compared to papilledema due to elevated ICP. Timely detection is crucial, and immediate symptomatic treatment followed by addressing the underlying cause is essential to prevent irreversible optic nerve damage and vision loss in cancer patients.
RESUMO
BACKGROUND: Medical students represent a highly educated population under significant pressures. They encounter multiple emotions during the transformation from insecure student to young knowledgeable physician. During the transition to clinical settings in the third year, the student may experience a loss of external control and may counter this with an increase in depression and/or anxiety symptoms. Studies suggest that mental health worsens after students begin medical school and remains poor throughout training. It is not just the undergraduate study period, which brings about these changes; it may continue later in internship, postgraduate study, and in physicians' practical life, and it may reach burnout level. The greater the psychosocial health, the greater is the well-being and the capacity for adaptation and overcoming problems and common life frustrations in family, relationships, and work. Medical students and practicing physicians, in comparison with the general population and that of other professions, are exposed to academic and professional stress and therefore are vulnerable to psychosocial health problems and certain specific dysfunctions that may compromise their physical, mental, and social health. OBJECTIVES: Our study examines the phenomenology of depression and anxiety in medical doctors in 3 government hospitals, 3 primary health care centers and the students (all years) and staff of Dubai Medical College for Girls (DMCG). SUBJECTS AND METHODS: This cross-sectional study was conducted in November 2008. One hundred sixty-five medical students of DMCG and 93 doctors (including medical staff of DMCG) completed a set of 2 questionnaires regarding Beck Depression Inventory (BDI) & Beck Anxiety Inventory (BAI). Results were analyzed using SPSS 11, and adequate statistical significant tests were done. A P value of <.05 was considered statistically significant. RESULTS: Of medical students, 28.6% showed depression and 28.7% showed anxiety. Of medical staff, 7.8% showed depression and 2.2% of them showed anxiety. The second-year medical students exhibited the highest percentage of depression and anxiety. There was a significant correlation between depression and anxiety among medical students (r = 0.6). "Crying" was the most common depressive symptom, and "fear of worst happening" was the most common anxiety manifestation in medical students. CONCLUSION: The considerable amount of depression and anxiety found among doctors and students in this study should trigger further work. Studies using more powerful designs would help to illuminate the factors leading to depression and anxiety.