Two new glassfrogs (Centrolenidae: Hyalinobatrachium) from Ecuador, with comments on the endangered biodiversity of the Andes.

Background: The Tropical Andes is the world's most biodiverse hotspot. This region contains >1,000 amphibian species, more than half of which are endemic. Herein we describe two new glassfrog species (Centrolenidae: Hyalinobatrachium) that we discovered within relatively unexplored and isolated localities of the Ecuadorian Andes. Methods: We employed morphological, acoustic, and molecular methods to test the hypothesis that Hyalinobatrachium mashpi sp. nov and H. nouns sp. nov. are species new to science. Following standard methods, we generated mitochondrial sequences (16S) of 37 individuals in the genus Hyalinobatrachium. We inferred the phylogenetic relationships of the two new species in comparison to all other glassfrogs using Maximum Likelihood. In addition to describing the call of H. mashpi sp. nov., we performed a discriminant analysis of principal components (DAPC) with the advertisement call characteristics of several congeners. Results: Based on an integrative taxonomy approach, we describe two new species. Morphological traits and the inferred phylogeny unambiguously place the new taxa in the genus Hyalinobatrachium. Both species are distinguished from other glassfrogs mainly by their dorsal coloration (i.e., dorsum lime green with small light yellow spots, head usually with interorbital bar) and transparent pericardium (i.e., the heart is visible through the ventral skin). The new species exhibit a high morphological similarity (i.e., cryptic) and occur within relatively close geographical proximity (closest aerial distance = 18.9 km); however, their uncorrected p distance for the mitochondrial gene 16S is 4.6-4.7%, a value that greatly exceeds the genetic distance between closely related species of centrolenid frogs. The DAPC revealed that the advertisement call of H. mashpi sp. nov. is acoustically distinct. Discussion: Our findings are congruent with several previous studies that report a high degree of endemism in the Toisán mountain range, which appears to be isolated from the main Andean cordillera for some amphibian groups. We recommend that both H. mashpi sp. nov. and H. nouns sp. nov. be listed as Endangered, following IUCN criteria. These new species provide another example of cryptic diversity in the Andes-further evidence that the region fosters much more biodiversity than we have the resources to catalog. Threatened by mining and other exploitative industries, these glassfrogs and many other yet-to-be-discovered Andean species highlight the dire need for effective conservation measures-especially in northwestern Ecuador.

Suicidal risks in rural versus urban populations in Sardinia.

OBJECTIVE: Rural locations have been associated with suicidal risk; low population density may be a relevant factor. Accordingly, we investigated hypothesized associations between suicidal ideation and behavior with selected geographic and population-related measures and other factors. METHODS: Consenting adult patients at a mood disorder center in Cagliari, Sardinia, were assessed for the presence of suicidal ideation and acts and their association with selected demographic and clinical factors as well as indicators of urbanicity and rurality, including distance from the region's main metropolitan area, population density, altitude, and population growth trends. RESULTS: Of 5,668 subjects, 27% had an indication of lifetime suicidal behavior or ideation; 8.6% had at least one suicidal act. Low population density, higher altitude and their interaction, distance from the metropolitan center of the main city (Cagliari), and population decline were associated with greater risk of suicidal ideation or behavior. In addition, and as expected, alcohol or substance abuse, diagnosis of mood disorders, higher depression ratings at intake, being younger at illness-onset, family history of suicide or other psychiatric disorder, being female, unmarried, separated or divorced, currently smoking cigarettes, being unemployed, and having experienced sexual abuse all were more likely in subjects with suicidal ideation or behavior. CONCLUSION: Suicidal ideation and behavior were associated with indicators of social isolation as well as with previously reported clinical and demographic risk factors.

Discovery of a Potent Dual SLK/STK10 Inhibitor Based on a Maleimide Scaffold.

SLK (STE20-like kinase) and STK10 (serine/threonine kinase 10) are closely related kinases whose enzymatic activity is linked to the regulation of ezrin, radixin, and moesin function and to the regulation of lymphocyte migration and the cell cycle. We identified a series of 3-anilino-4-arylmaleimides as dual inhibitors of SLK and STK10 with good kinome-wide selectivity. Optimization of this series led to multiple SLK/STK10 inhibitors with nanomolar potency. Crystal structures of exemplar inhibitors bound to SLK and STK10 demonstrated the binding mode of the inhibitors and rationalized their selectivity. Cellular target engagement assays demonstrated the binding of the inhibitors to SLK and STK10 in cells. Further selectivity analyses, including analysis of activity of the reported inhibitors against off-targets in cells, identified compound 31 as the most potent and selective inhibitor of SLK and STK10 yet reported.

A new glassfrog (Centrolenidae) from the Chocó-Andean Río Manduriacu Reserve, Ecuador, endangered by mining.

We describe a new glassfrog from Río Manduriacu Reserve, Imbabura Province, on the Pacific slopes of the Ecuadorian Andes. The new species can be distinguished from most other glassfrogs by having numerous yellow spots on the dorsum and lacking membranes among fingers. Both morphological and molecular data support the placement of the species in the genus Nymphargus. We present a new mitochondrial phylogeny of Nymphargus and discuss the speciation patterns of this genus; most importantly, recent speciation events seem to result from the effect of the linearity of the Andes. Finally, although the new species occurs within a private reserve, it is seriously endangered by mining activities; thus, following IUCN criteria, we consider the new species as Critically Endangered.

Osteoporosis: a clinical and pharmacological update.

Osteoporosis is characterized by the loss of bone mass, deterioration of the bone microarchitecture, and an increased risk of fractures; these later complications are associated with significant morbidity and mortality. The asymptomatic and progressive nature of osteoporosis underscores the importance of identifying this entity in early stages. Despite the various treatments available, the prevention of the disease represents the most important aspect of management. An adequate intake of calcium and vitamin D as well as a healthy lifestyle is the basis for maintaining bone health. When osteoporosis is diagnosed, the choice of medications must be individualized considering characteristics of the patient and the risk of fractures. In this article, we review the main causes of osteoporosis, when and how to start treatment, and appropriate therapy and monitoring.

Baseline Prolonged PR Interval and Outcome of Cardiac Resynchronization Therapy: A Systematic Review and Meta-analysis / Intervalo PR Basal Prolongado e Desfecho da Terapia de Ressincronização Cardíaca: Revisão Sistemática e Meta-Análise

Abstract Background: Recent studies suggest that baseline prolonged PR interval is associated with worse outcome in cardiac resynchronization therapy (CRT). However, a systematic review and meta-analysis of the literature have not been made. Objective: To assess the association between baseline prolonged PR interval and adverse outcomes of CRT by a systematic review of the literature and a meta-analysis. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2017. The included studies were published prospective or retrospective cohort studies that compared all-cause mortality, HF hospitalization, and composite outcome of CRT with baseline prolonged PR (> 200 msec) versus normal PR interval. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals. Results: Six studies from January 1991 to May 2017 were included in this meta-analysis. All-cause mortality rate is available in four studies involving 17,432 normal PR and 4,278 prolonged PR. Heart failure hospitalization is available in two studies involving 16,152 normal PR and 3,031 prolonged PR. Composite outcome is available in four studies involving 17,001 normal PR and 3,866 prolonged PR. Prolonged PR interval was associated with increased risk of all-cause mortality (pooled risk ratio = 1.34, 95 % confidence interval: 1.08-1.67, p < 0.01, I2= 57.0%), heart failure hospitalization (pooled risk ratio = 1.30, 95 % confidence interval: 1.16-1.45, p < 0.01, I2= 6.6%) and composite outcome (pooled risk ratio = 1.21, 95% confidence interval: 1.13-1.30, p < 0.01, I2= 0%). Conclusions: Our systematic review and meta-analysis support the hypothesis that baseline prolonged PR interval is a predictor of all-cause mortality, heart failure hospitalization, and composite outcome in CRT patients.

Resumo Fundamento: Estudos recentes sugerem que intervalo PR basal prolongado está associado a prognóstico ruim para a terapia de ressincronização cardíaca (TRC). No entanto, nunca foram feitas uma revisão sistemática e meta-análise da literatura. Objetivo: Avaliar a associação entre intervalo PR basal prolongado e resultados adversos da TRC por meio de uma revisão sistemática e meta-análise da literatura. Métodos: Pesquisamos de forma abrangente os bancos de dados MEDLINE e EMBASE, desde o início até março de 2017. Os estudos incluídos eram de coorte prospectivos ou retrospectivos que comparavam mortalidade por todas as causas, hospitalização por insuficiência cardíaca e desfecho composto por TRC com PR basal prolongado (> 200 ms) versus intervalo PR normal. Os dados de cada estudo foram combinados pelo modelo de efeitos aleatórios, variância genérica inversa de DerSimonian e Laird para calcular as razões de risco e os intervalos de confiança de 95% (IC95%). Resultados: Foram incluídos seis estudos de janeiro de 1991 a maio de 2017 nesta metanálise. A taxa de mortalidade por todas as causas foi mencionada em quatro estudos envolvendo 17.432 intervalos PR normais e 4.278 prolongados. Hospitalização por insuficiência cardíaca foi abordada em dois estudos envolvendo 16.152 PR normais e 3.031 prolongados. Desfecho composto esteve presente em quatro estudos com 17.001 PR normais e 3.866 prolongadas. Intervalo PR prolongado foi associado a risco aumentado de mortalidade por todas as causas (razão de risco agrupado = 1,34, IC95%: 1,08-1,67, p < 0,01, I2= 57,0%), hospitalização por insuficiência cardíaca (razão de risco agrupado = 1,30, 95 % de IC95%: 1,16-1,45, p < 0,01, I2= 6,6%) e desfecho composto (razão de risco agrupado = 1,21, IC95%: 1,13-1,30, p < 0,01, I2= 0%). Conclusões: Nossa revisão sistemática e metanálise suportam a hipótese de que o intervalo PR basal prolongado é um preditor de mortalidade por todas as causas, hospitalização por insuficiência cardíaca e desfecho composto em pacientes submetidos à TRC.

Baseline Prolonged PR Interval and Outcome of Cardiac Resynchronization Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies suggest that baseline prolonged PR interval is associated with worse outcome in cardiac resynchronization therapy (CRT). However, a systematic review and meta-analysis of the literature have not been made. OBJECTIVE: To assess the association between baseline prolonged PR interval and adverse outcomes of CRT by a systematic review of the literature and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2017. The included studies were published prospective or retrospective cohort studies that compared all-cause mortality, HF hospitalization, and composite outcome of CRT with baseline prolonged PR (> 200 msec) versus normal PR interval. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals. RESULTS: Six studies from January 1991 to May 2017 were included in this meta-analysis. All-cause mortality rate is available in four studies involving 17,432 normal PR and 4,278 prolonged PR. Heart failure hospitalization is available in two studies involving 16,152 normal PR and 3,031 prolonged PR. Composite outcome is available in four studies involving 17,001 normal PR and 3,866 prolonged PR. Prolonged PR interval was associated with increased risk of all-cause mortality (pooled risk ratio = 1.34, 95 % confidence interval: 1.08-1.67, p < 0.01, I2= 57.0%), heart failure hospitalization (pooled risk ratio = 1.30, 95 % confidence interval: 1.16-1.45, p < 0.01, I2= 6.6%) and composite outcome (pooled risk ratio = 1.21, 95% confidence interval: 1.13-1.30, p < 0.01, I2= 0%). CONCLUSIONS: Our systematic review and meta-analysis support the hypothesis that baseline prolonged PR interval is a predictor of all-cause mortality, heart failure hospitalization, and composite outcome in CRT patients.

A marvelous new glassfrog (Centrolenidae, Hyalinobatrachium) from Amazonian Ecuador.

Hyalinobatrachium is a behaviorally and morphologically conserved genus of Neotropical anurans, with several pending taxonomic problems. Using morphology, vocalizations, and DNA, a new species from the Amazonian lowlands of Ecuador is described and illustrated. The new species, Hyalinobatrachium yakusp. n., is differentiated from all other congenerics by having small, middorsal, dark green spots on the head and dorsum, a transparent pericardium, and a tonal call that lasts 0.27-0.4 s, with a dominant frequency of 5219.3-5329.6 Hz. Also, a mitochondrial phylogeny for the genus is presented that contains the new species, which is inferred as sister to H. pellucidum. Conservation threats to H. yakusp. n. include habitat destruction and/or pollution mainly because of oil and mining activities.

Resumen Hyalinobatrachium es un género de ranas Neotropicales con una morfología y comportamiento sumamente conservados, y con varios problemas taxonómicos no resueltos. Utilizando datos morfológicos, cantos y ADN, en el presente trabajo describimos una nueva especie de las tierras bajas de la Amazonía del Ecuador. La nueva especie, Hyalinobatrachium yakusp. n., se diferencia de todos sus congenéricos por tener una serie de puntos mediodorsales color verde oscuros en la cabeza y cuerpo, pericardio transparente, y un canto tonal con una duración de 0.27­0.4 s, con una frecuencia dominante 5219.3­5329.6 Hz. También presentamos una filogenia mitocondrial del género, la cual incluye la nueva especie y a su especie hermana, H. pellucidum. Las amenazas de conservación para H. yakusp. n. incluyen principalmente la destrucción y/o contaminación del hábitat debido a actividades mineras y petroleras.

Rol de la ecografía en la evaluación de la cortical ósea / Role of ultrasound in the evaluation of the bone cortex

La ecografía es el método de elección para la evaluación inicial de las partes blandas y el sistema muscular, siendo una técnica accesible, portátil y de bajo costo. Sin embargo, ha sido excluida de la exploración y evaluación de las patologías óseas debido a la idea de que es incapaz de penetrar la superficie del hueso. De hecho, muchos radiólogos admiten que esta es una de las pocas localizaciones donde la ecografía no resulta efectiva. Si bien algunos de estos conceptos son ciertos, este método puede aportar valiosa información diagnóstica sobre el estado del hueso, principalmente sobre la cortical ósea, en variadas circunstancias. La ecografía de la cortical ósea es posible por el artefacto de reflexión hiperecogénico lineal y regular que esta genera. En manos experimentadas, el reconocimiento y exploración de la superficie ósea permiten obtener datos muy útiles. Los tumores óseos generan reacciones periósticas fácilmente observables y caracterizables por ultrasonido, con la ventaja adicional de que el Doppler color identifica la vascularización del tumor. Las fracturas se observan como disrupciones de la cortical y la patología degenerativa se puede sospechar ante irregularidades corticales. Asimismo, es posible reconocer patologías como avulsiones, callos óseos de procesos previos e incluso fracturas por estrés. En este ensayo iconográfico mostramos diferentes casos de ecografías de partes blandas que evidenciaron hallazgos patológicos en la cortical ósea, permitiendo arribar a un diagnóstico o guiando en la elección de un estudio adicional.

Ultrasound is the best choice to evaluate soft tissues and the muscular system because of its accessibility, low cost and portability. Historically, the assumption has been that because ultrasound waves cannot penetrate bone, it is not useful in the evaluation of the skeletal system and its diseases. Radiologists admit that one of the very few tissue types which ultrasound cannot evaluate is bone. There is, of course, much truth in this, but recent studies suggest that ultrasound can provide valuable diagnostic information regarding the state of bone in some circumstances. The high reflectivity of sound at the bone-soft tissue interface is what allows the bone surface to be visualised. Valuable diagnostic information can be obtained by exploring bone surface in detail. The fact that bone tumours manifest themselves as periosteal reactions makes them easily recognisable by ultrasound, with the additional advantage if using Doppler colour. Bone fractures could be seen as interruptions of the bone continuity, and degenerative diseases should be suspected when an irregular surface is observed. Likewise, other pathologies such as avulsion fractures, bone callus stemming from previous processes, and even stress fractures can be identified. In this pictorial essay different cases are presented of musculoskeletal ultrasound in which bone surface was evaluated and abnormalities discovered, making a diagnosis or suggesting an additional test.

Major depression in hospitalized Argentine general medical patients: Prevalence and risk factors.

BACKGROUND: Depression is not uncommon among medically hospitalized patients, though reported prevalence has varied widely, often in samples involving elderly patients with particular illnesses. Accordingly, we evaluated risk of major depression in three metropolitan general hospitals in Buenos Aires, in subjects with a range of medical disorders and ages, comparing several standard screening methods to expert clinical examinations. METHODS: Consecutively hospitalized general medical patients were evaluated over a six-months. Excluded were subjects under age 18 and those unable to participate in assessments because of illness, medication, sensory or speech impairment, or lack of language fluency, or scored <25 on the Mini Mental State Examination (MMSE). Consenting participants were examined for DSM-IV-TR major depression by psychiatrists guided by MINI examinations, compared with other standard screening methods. Risk factors were assessed by preliminary bivariate analyses followed by multivariate logistic regression modeling. RESULTS: Overall prevalence of major depression in 257 subjects was 27% by psychiatric examination. The rate was most similar (25%) with the Hospital Anxiety & Depression Scale (HADS), and much higher with the Beck Depression Inventory-II (BDI, 44%) and Patient Health Questionnaire (PHQ, 56%). Factors associated independently with depression by multivariate modeling included: prior psychotropic-drug treatment, female sex, more children, and heavy smoking. Depression was associated most with neoplastic, urological, and infectious disorders, least with pulmonary, neurological, and hematologic conditions. LIMITATIONS: Modest numbers limited power to test for associations of depression with specific medical conditions. CONCLUSIONS: Major depression was identified in over one-quarter of Argentine, general medical inpatients, with marked differences among screening methods. Several risk factors were identified. The findings encourage assertive identification of depression in hospitalized medical patients using valid, reliable, and cost-effective means of improving their care.

Use of preoperative embolization prior to transplant nephrectomy

ABSTRACT Introduction After a failed transplant, management of a non-functional graft with pain or recurrent infections can be challenging. Transplant nephrectomy (TN) can be a morbid procedure with the potential for significant blood loss. Embolization of the renal artery alone has been proposed as a method of reducing complications from an in vivo failed kidney transplant. While this does yield less morbidity, it may not address an infected graft or refractory hematuria or rejection. We elected to begin preoperative embolization to assess if this would help decrease the blood loss and transfusion rate associated with TN. Materials and Methods We performed a retrospective analysis of all patients who underwent non-emergent TN at our institution. Patients who had functioning grafts that later failed were included in analysis. TN was performed for recurrent infections, pain or hematuria. We evaluated for blood loss (EBL) during TN, transfusion rate and length of hospital stay. Results A total of 16 patients were identified. Nine had preoperative embolization or no blood flow to the graft prior to TN. The remaining 7 did not have preoperative embolization. The shortest time from transplant to TN was 8 months and the longest 18 years with an average of 6.3 years. Average EBL for the embolized patients (ETN) was 143.9cc compared to 621.4cc in the non-embolized (NETN) group (p=0.041). Average number of units of blood transfused was 0.44 in the ETN with only 3/9 patients requiring transfusion. The NETN patients had average of 1.29 units transfused with 5/7 requiring transfusion. The length of stay was longer for the ETN (5.4 days) compared to 3.9 in the NETN. No intraoperative complications were seen in either group and only one patient had a postoperative ileus in the NETN. Conclusion Embolization prior to TN significantly decreases the EBL but does not significantly decrease transfusion rate. However, patients do require a significantly longer hospitalization with embolization due to the time needed for embolization. Larger studies are needed to determine if embolization before transplant nephrectomy reduces the transfusion rates and overall complications.

Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012).

The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.

Co-occurrence of anxiety and bipolar disorders: clinical and therapeutic overview.

BACKGROUND: Anxiety commonly co-occurs with bipolar disorders (BDs), but the significance of such "co-morbidity" remains to be clarified and its optimal treatment adequately defined. METHODS: We reviewed epidemiological, clinical, and treatment studies of the co-occurrence of BD and anxiety disorder through electronic searching of Pubmed/MEDLINE and EMBASE databases. RESULTS: Nearly half of BD patients meet diagnostic criteria for an anxiety disorder at some time, and anxiety is associated with poor treatment responses, substance abuse, and disability. Reported rates of specific anxiety disorders with BD rank: panic ≥ phobias ≥ generalized anxiety ≥ posttraumatic stress ≥ obsessive-compulsive disorders. Their prevalence appears to be greater among women than men, but similar in types I and II BD. Anxiety may be more likely in depressive phases of BD, but relationships of anxiety phenomena to particular phases of BD, and their temporal distributions require clarification. Adequate treatment trials for anxiety syndromes in BD patients remain rare, and the impact on anxiety of treatments aimed at mood stabilization is not clear. Benzodiazepines are sometimes given empirically; antidepressants are employed cautiously to limit risks of mood switching and emotional destabilization; lamotrigine, valproate, and second-generation antipsychotics may be useful and relatively safe. CONCLUSIONS: Anxiety symptoms and syndromes co-occur commonly in patients with BD, but "co-morbid" phenomena may be part of the BD phenotype rather than separate illnesses.

Lithium in Psychiatry / Litio en Psiquiatría

Background: Lithium is a light, metallic element and minerals containing it are most abundant in the Andes. John Cade introduced lithium carbonate for the treatment of mania in 1949, opening the era of modern clinical psychopharmacology. Lithium remains the most extensively studied mood-stabilizing agent. It has had a revolutionary impact in supporting bipolar manic-depressive disorder as a discrete diagnosis, and on psychiatric therapeutics. Methods: We survey the development of lithium treatment in psychiatry, including findings concerning effects on suicide. Results: Lithium is the most extensively studied treatment for bipolar disorder and the prototypical mood-stabilizing agent, despite emergence of anticonvulsants and modern antipsychotics. In addition to limiting recurrences of mania, and some reduction of recurrences of bipolar depression, lithium has demonstrated protective effects against suicide. All treatments for bipolar disorder have notable limitations, including sometimes serious adverse effects, incomplete prevention of recurrences of mania and limited prevention of depression, which accounts for three-quarters of the approximately 50% time-ill in long-term follow-up with standard treatments. Lithium can be toxic in untreated overdoses; safe dosing requires monitoring of serum concentrations. Lithium also may have mild teratogenic effects, but far less than those of anticonvulsants used for bipolar disorder. Conclusions: Lithium opened the era of modern psychopharmacology and continues as the best-established mood-stabilizing treatment for bipolar disorder as well as having strong evidence of suicide-preventing effects.

Antecedentes: Litio es un elemento metálico ligero y los minerales que lo contienen abundan predominantementeen la región andina. John Cade introdujo el uso de carbonato de litio para el tratamiento de manía en 1949, iniciando con ello la era de la moderna psicofarmacología clínica. Litio se mantiene como el más extensamente estudiando agente estabilizador del ánimo. Ha tenido un impacto revolucionario en la preservación del trastorno maniaco-depresivo o bipolar como un diagnóstico discreto y en el campo de la terapéutica psiquiátrica.Métodos: Se examina el desarrollo histórico del tratamiento con litio en psiquiatría, incluyendo hallazgos en relación a su efecto sobreconducta suicida. Hallazgos:Litio es el tipo de tratamiento más extensamente estudiado en el manejo de trastorno bipolar disorder, constituido como el prototipo de agente estabilizador del ánimo, a pesar de la emergencia de agentes anticonvulsivantes y de los antipsicóticos modernos. Además de limitar la recurrencia de episodios maniacos y reducir en algo las recurrencias de depresión bipolar, litio ha demostrado efectos protectores en relación a suicidio y conducta suicida. Todos los tipos de tratamiento de trastorno bipolar tienen limitaciones notables, incluyendo algunas veces serios efectos adversos, prevención incompleta de recurrencias de manía y prevención limitada de depresión, todo lo cual constituye las tres cuartas partes de aproximadamente el 50 % de tiempo con enfermedad en estudios de seguimiento a largo plazo con tratamientos estándar.