A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer's disease (ART-AD).

Retrotransposons are viral-like DNA sequences that constitute approximately 41% of the human genome. Studies in Drosophila, mice, cultured cells, and human brain indicate that retrotransposons are activated in settings of tauopathy, including Alzheimer's disease, and causally drive neurodegeneration. The anti-retroviral medication 3TC (lamivudine), a nucleoside analog reverse transcriptase inhibitor, limits retrotransposon activation and suppresses neurodegeneration in tau transgenic Drosophila, two mouse models of tauopathy, and in brain assembloids derived from patients with sporadic Alzheimer's disease. We performed a 24-week phase 2a open-label clinical trial of 300 mg daily oral 3TC (NCT04552795) in 12 participants aged 52-83 years with a diagnosis of mild cognitive impairment due to suspected Alzheimer's disease. Primary outcomes included feasibility, blood brain barrier penetration, effects of 3TC on reverse transcriptase activity in the periphery, and safety. Secondary outcomes included changes in cognition and fluid-based biomarkers of neurodegeneration and neuroinflammation. All participants completed the six-month trial; one event of gastrointestinal bleeding due to a peptic ulcer was reported. 3TC was detected in blood and cerebrospinal fluid (CSF) of all participants, suggestive of adherence to study drug and effective brain penetration. Cognitive measures remained stable throughout the study. Glial fibrillary acidic protein (GFAP) (P=0.03) and Flt1 (P=0.05) were significantly reduced in CSF over the treatment period; Aß42/40 (P=0.009) and IL-15 (P=0.006) were significantly elevated in plasma. While this is an open label study of small sample size, the significant decrease of some neurodegeneration- and neuroinflammation-related biomarkers in CSF, significantly elevated levels of plasma Aß42/40, and a trending decrease of CSF NfL after six months of 3TC exposure suggest a beneficial effect on subjects with mild cognitive impairment due to suspected Alzheimer's disease. Feasibility, safety, tolerability, and central nervous system (CNS) penetration assessments further support clinical evaluation of 3TC in a larger placebo-controlled, multi-dose clinical trial.

m6A-dependent circular RNA formation mediates tau-induced neurotoxicity.

Circular RNAs (circRNAs), covalently closed RNA molecules that form due to back-splicing of RNA transcripts, have recently been implicated in Alzheimer's disease and related tauopathies. circRNAs are regulated by N6-methyladenosine (m6A) RNA methylation, can serve as "sponges" for proteins and RNAs, and can be translated into protein via a cap-independent mechanism. Mechanisms underlying circRNA dysregulation in tauopathies and causal relationships between circRNA and neurodegeneration are currently unknown. In the current study, we aimed to determine whether pathogenic forms of tau drive circRNA dysregulation and whether such dysregulation causally mediates neurodegeneration. We identify circRNAs that are differentially expressed in the brain of a Drosophila model of tauopathy and in induced pluripotent stem cell (iPSC)-derived neurons carrying a tau mutation associated with autosomal dominant tauopathy. We leverage Drosophila to discover that depletion of circular forms of muscleblind (circMbl), a circRNA that is particularly abundant in brains of tau transgenic Drosophila, significantly suppresses tau neurotoxicity, suggesting that tau-induced circMbl elevation is neurotoxic. We detect a general elevation of m6A RNA methylation and circRNA methylation in tau transgenic Drosophila and find that tau-induced m6A methylation is a mechanistic driver of circMbl formation. Interestingly, we find that circRNA and m6A RNA accumulate within nuclear envelope invaginations of tau transgenic Drosophila and in iPSC-derived cerebral organoid models of tauopathy. Taken together, our studies add critical new insight into the mechanisms underlying circRNA dysregulation in tauopathy and identify m6A-modified circRNA as a causal factor contributing to neurodegeneration. These findings add to a growing literature implicating pathogenic forms of tau as drivers of altered RNA metabolism.

Moesin is an effector of tau-induced actin overstabilization, cell cycle activation, and neurotoxicity in Alzheimer's disease.

In Alzheimer's disease, neurons acquire phenotypes that are also present in various cancers, including aberrant activation of the cell cycle. Unlike cancer, cell cycle activation in post-mitotic neurons is sufficient to induce cell death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer's disease and related "tauopathies." Here we combine network analyses of human Alzheimer's disease and mouse models of Alzheimer's disease and primary tauopathy with studies in Drosophila to discover that pathogenic forms of tau drive cell cycle activation by disrupting a cellular program involved in cancer and the epithelial-mesenchymal transition (EMT). Moesin, an EMT driver, is elevated in cells harboring disease-associated phosphotau, over-stabilized actin, and ectopic cell cycle activation. We further find that genetic manipulation of Moesin mediates tau-induced neurodegeneration. Taken together, our study identifies novel parallels between tauopathy and cancer.

Pathogenic tau-induced transposable element-derived dsRNA drives neuroinflammation.

Deposition of tau protein aggregates in the brain of affected individuals is a defining feature of "tauopathies," including Alzheimer's disease. Studies of human brain tissue and various model systems of tauopathy report that toxic forms of tau negatively affect nuclear and genomic architecture, identifying pathogenic tau-induced heterochromatin decondensation and consequent retrotransposon activation as a causal mediator of neurodegeneration. On the basis of their similarity to retroviruses, retrotransposons drive neuroinflammation via toxic intermediates, including double-stranded RNA (dsRNA). We find that dsRNA and dsRNA sensing machinery are elevated in astrocytes of postmortem brain tissue from patients with Alzheimer's disease and progressive supranuclear palsy and in brains of tau transgenic mice. Using a Drosophila model of tauopathy, we identify specific tau-induced retrotransposons that form dsRNA and find that pathogenic tau and heterochromatin decondensation causally drive dsRNA-mediated neurodegeneration and neuroinflammation. Our study suggests that pathogenic tau-induced heterochromatin decondensation and retrotransposon activation cause elevation of inflammatory, transposable element-derived dsRNA in the adult brain.

Tau-Induced Elevation of the Activity-Regulated Cytoskeleton Associated Protein Arc1 Causally Mediates Neurodegeneration in the Adult Drosophila Brain.

Alzheimer's disease and other tauopathies are neurodegenerative disorders pathologically defined by aggregated forms of tau protein in the brain. While synaptic degradation is a well-established feature of tau-induced neurotoxicity, the underlying mechanisms of how pathogenic forms of tau drive synaptic dysfunction are incompletely understood. Synaptic function and subsequent memory consolidation are dependent upon synaptic plasticity, the ability of synapses to adjust their structure and strength in response to changes in activity. The activity regulated cytoskeleton associated protein ARC acts in the nucleus and at postsynaptic densities to regulate various forms of synaptic plasticity. ARC harbors a retrovirus-like Gag domain that facilitates ARC multimerization and capsid formation. Trans-synaptic transfer of RNA-containing ARC capsids is required for synaptic plasticity. While ARC is elevated in brains of patients with Alzheimer's disease and genetic variants in ARC increase susceptibility to Alzheimer's disease, mechanistic insight into the role of ARC in Alzheimer's disease is lacking. Using a Drosophila model of tauopathy, we find that pathogenic tau significantly increases multimeric species of the protein encoded by the Drosophila homolog of ARC, Arc1, in the adult fly brain. We find that Arc1 is elevated within nuclei and the neuropil of tau transgenic Drosophila, but does not localize to synaptic vesicles or presynaptic terminals. Lastly, we find that genetic manipulation of Arc1 modifies tau-induced neurotoxicity, suggesting that tau-induced Arc1 elevation mediates neurodegeneration. Taken together, our results suggest that ARC elevation in human Alzheimer's disease is a consequence of tau pathology and is a causal factor contributing to neuronal death.

Tau-induced deficits in nonsense-mediated mRNA decay contribute to neurodegeneration.

INTRODUCTION: While brains of patients with Alzheimer's disease and related tauopathies have evidence of altered RNA processing, we lack a mechanistic understanding of how altered RNA processing arises in these disorders and if such changes are causally linked to neurodegeneration. METHODS: Using Drosophila melanogaster models of tauopathy, we find that overall activity of nonsense-mediated mRNA decay (NMD), a key RNA quality-control mechanism, is reduced. Genetic manipulation of NMD machinery significantly modifies tau-induced neurotoxicity, suggesting that deficits in NMD are causally linked to neurodegeneration. Mechanistically, we find that deficits in NMD are a consequence of aberrant RNA export and RNA accumulation within nuclear envelope invaginations in tauopathy. We identify a pharmacological activator of NMD that suppresses neurodegeneration in tau transgenic Drosophila, indicating that tau-induced deficits in RNA quality control are druggable. DISCUSSION: Our studies suggest that NMD activators should be explored for their potential therapeutic value to patients with tauopathies.

TauLUM, an in vivo Drosophila sensor of tau multimerization, identifies neuroprotective interventions in tauopathy.

Tau protein aggregates are a defining neuropathological feature of "tauopathies," a group of neurodegenerative disorders that include Alzheimer's disease. In the current study, we develop a Drosophila split-luciferase-based sensor of tau-tau interaction. This model, which we term "tauLUM," allows investigators to quantify tau multimerization at individual time points or longitudinally in adult, living animals housed in a 96-well plate. TauLUM causes cell death in the adult Drosophila brain and responds to both pharmacological and genetic interventions. We find that transgenic expression of an anti-tau intrabody or pharmacological inhibition of HSP90 reduces tau multimerization and cell death in tauLUM flies, establishing the suitability of this system for future drug and genetic modifier screening. Overall, our studies position tauLUM as a powerful in vivo discovery platform that leverages the advantages of the Drosophila model organism to better understand tau multimerization.

Genome-wide association study and functional validation implicates JADE1 in tauopathy.

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-ß (Aß) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aß toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

Provision of mental health services immediately following a natural disaster: Experiences after Hurricane Maria in Puerto Rico.

OBJECTIVE: The increased risk of mental health disorders in the months and years following a natural disaster highlights the need for more immediate preventive intervention. The objective of the current study was to learn from a real-time implementation of a natural disaster response following the Hurricane Maria in Puerto Rico to identify strategies for providing mental health services immediately after a natural disaster. METHODS: Two focus groups were held with faculty (n = 6) and graduate students (n = 4) from a graduate psychology program at the Universidad Carlos Albizu, Centro Universitario Mayagüez. An additional key informant interview was conducted with two faculty member participants. Data were analyzed qualitatively using thematic analysis. RESULTS: The delivery of mental health services was organized into three major themes: (1) finding a way to communicate, (2) targeting key access points for outreach and centralization of resources, and (3) providing triaged mental health care based on level of need. CONCLUSIONS: Findings are used to guide recommendations for mental health response preparation in future natural disaster contexts.

Emerging roles of CCM genes during tumorigenesis with potential application as novel biomarkers across major types of cancers.

Cerebral cavernous malformations (CCMs) are microvascular anomalies in the brain that result in increased susceptibility to stroke. Three genes have been identified as causes of CCMs: cerebral cavernous malformations 1 [(CCM1) also termed Krev interaction trapped 1 (KRIT1)], cerebral cavernous malformation 2 [(CCM2) also termed MGC4607] and cerebral cavernous malformation 3 [(CCM3) also termed programmed cell death 10 (PDCD10)]. It has been demonstrated that both CCM1 and CCM3 bind to CCM2 to form a CCM signaling complex (CSC) with which to modulate multiple signaling cascades. CCM proteins have been reported to play major roles in microvascular angiogenesis in human and animal models. However, CCM proteins are ubiquitously expressed in all major tissues, suggesting an unseen broader role of the CSC in biogenesis. Recent evidence suggests the possible involvement of the CSC complex during tumorigenesis; however, studies concerning this aspect are limited. This is the first report to systematically investigate the expression patterns of CCM proteins in major human tumors using real­time quantitative PCR, RNA­fluorescence in situ hybridization, immunohistochemistry and multicolor immunofluorescence imaging. Our data demonstrated that differential expression patterns of the CSC complex are correlated with certain types and grades of major human cancers, indicating the potential application of CCM genes as molecular biomarkers for clinical oncology. Our data strongly suggest that more efforts are needed to elucidate the role of the CSC complex in tumorigenesis, which may have enormous clinical potential for cancer diagnostic, prognostic and therapeutic applications.

Testosterone induces hyporesponsiveness by interfering with IP3 receptors in guinea pig airway smooth muscle.

Asthma symptoms have been associated with sex steroids. During childhood, this illness seems more frequent in boys than in girls and this tendency reverts in puberty when it is more severe in women. Testosterone (TES), at supraphysiological concentrations, relaxed pre-contracted airway smooth muscle, but its effects at physiological concentrations have not been thoroughly studied. We explored this possibility in guinea pig tracheal smooth muscle. In myocytes TES (10 nM) abolished carbachol (CCh)-induced intracellular Ca2+ concentration ([Ca2+]i) increment. Ca2+ responses to ATP were partially modified by TES while histamine's were not. These results indicate that inositol 1,4,5-trisphosphate (IP3) signaling pathway might be involved. Photolysis of caged-IP3 increased [Ca2+]i and TES abolished this effect. TES diminished reactivity of the smooth muscle to CCh and this effect was non-genomic since it was unchanged by flutamide. In tracheal smooth muscle, mRNA for each IP3 receptor (ITPR) isoform was found and, by immunofluorescence, ITPR1 and ITPR3 seems to be the main isoforms observed while ITPR2 was less prominent. Comparing the amino acid sequence of ITPR1 and the sequence of the TES binding site on the androgen receptor, we found that they share a short sequence. This domain could be responsible for the TES binding to the ITPR1 and probably for its blocking effect. We conclude that TES modifies ITPR1 function in airway smooth muscle, turning this tissue less reactive to contractile agonists that act through PLCß-IP3 signaling cascade. These results might be related to the low asthma prevalence in males from puberty to adulthood.

Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca2+ basal levels.

Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17ß-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca2+ channel (L-VDCC, D-600) and store operated Ca2+ channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca2+ concentrations (b[Ca2+]i) as D-600+2-APB but to a higher extend. TES after D-600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3), further decreased b[Ca2+]i rendering this response equal to TES alone. With indomethacin, the b[Ca2+]i decrease induced by the blockade of L-VDCC and TRPC3 was not changed by the addition of TES. PGE2 or forskolin addition after D600+2-APB, decreased b[Ca2+]i resembling TES response. An adenylate cyclase inhibitor followed by D-600+2-APB lowered b[Ca2+]i, TES showed no further effect. Carbachol-induced [Ca2+]i increment was reduced by TES or DHEA. 17ß-estradiol diminished KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward Ca2+ current. CONCLUSION: DHEA and TES diminish ASM tone and b[Ca2+]i by blocking L-VDCC and probably a constitutively active TRPC3, and by PGE2 synthesis. E2 lowers ASM basal tone by blocking only L-VDCC.

Testosterone-induced relaxation involves L-type and store-operated Ca2+ channels blockade, and PGE 2 in guinea pig airway smooth muscle.

In vascular smooth muscle, it has been described that testosterone (TES) produces relaxation by blocking L-type Ca(2+) channels. Recently, we found that L-type Ca(2+) and store-operated Ca(2+) (SOC) channels are the main membranal structures that provide extracellular Ca(2+) for carbachol (CCh)-induced contraction in airway smooth muscle (ASM). We studied the possible interactions between L-type and SOC channels in TES-induced relaxation in guinea pig ASM. TES (10, 32, 100, and 178 µM) induced a complete relaxation of CCh-precontracted tracheal smooth muscle, and indomethacin partially inhibited this response. In single myocytes, the KCl-induced intracellular Ca(2+) increase ([Ca(2+)]i) was decreased by 32 and completely blocked by 100 nM TES. This androgen (32 and 100 µM) significantly diminished (~25 and 49 %, respectively) the capacitative Ca(2+) entry. Myocytes stimulated with CCh produced a transient Ca(2+) peak followed by a sustained plateau. D-600 was added during the plateau phase, and a partial diminution (~35 %) was observed. A greater decrease (~78 %) was seen when 2-aminoethyl diphenylborinate (2-APB, SOC antagonist) was used. The combination of both drugs completely abolished the Ca(2+) plateau induced by CCh. TES (100 µM) also completely abolished the CCh-induced Ca(2+) plateau. Indomethacin significantly diminished this effect of TES. PGE2 and butaprost proportionally decreased the Ca(2+) plateau as indomethacin blocked it. Sarcoplasmic reticulum refilling was partially, dependently, and significantly diminished by TES. We concluded that TES-induced relaxation involves blockade of L-type Ca(2+) channels at nanomolar and SOC channels at micromolar concentration and PGE2 seems to be also involved in this phenomenon.

La sugestión como parte de un sistema terapéutico integrado en un grupo de adolescentes fumadores y consumidores de alcohol / The suggestion as part of an integrated therapeutic system in a group of adolescent smokers and drinkers

Se realizó un estudio de intervención, mediante un sistema terapéutico integrado, en 12 adolescentes fumadores y consumidores de alcohol, pertenecientes al poblado de Boniato, atendidos por los integrantes del equipo de salud mental del Policlínico Ernesto Guevara de la Serna de Santiago de Cuba, desde enero hasta julio de 2013, a fin de lograr la deshabituación y mejorar la conducta ante los tóxicos. Se utilizaron las psicoterapias de grupo e individual, además de la sugestión como técnica afín a la hipnosis. En la casuística predominaron: el grupo de 14-16 años, con primacía del sexo masculino, los trastornos mentales como antecedentes patológicos personales (58,3 por ciento), el consumo de sustancias como antecedente patológico familiar y los que consumían frecuentemente (66,6 por ciento). Se logró la deshabituación en 2 de ellos, disminuyó el consumo en 7 y solo 3 se mantuvieron igual(AU)

An intervention study by means of an integrated therapeutic system was carried out in 12 adolescent smokers and drinkers, belonging to Boniato village, attended by the mental health team of Ernesto Guevara de la Serna Polyclinic of Santiago de Cuba, from January to July 2013, in order to achieve detoxification and improve conduct related to toxic habits. Group and individual psychotherapies were used, and the suggestion as a technique related to hypnosis. The age group of 14-16 years, with predominance of the male sex, mental disorders as medical history (58.3 percent), use of substances as family history and those who consumed frequently (66.6 percent) predominated in the case material. Detoxification was achieved in 2 of them, consumption decreased in 7 and only 3 remained the same.

La sugestión como parte de un sistema terapéutico integrado en un grupo de adolescentes fumadores y consumidores de alcohol / The suggestion as part of an integrated therapeutic system in a group of adolescent smokers and drinkers i: en

Se realizó un estudio de intervención, mediante un sistema terapéutico integrado, en 12 adolescentes fumadores y consumidores de alcohol, pertenecientes al poblado de Boniato, atendidos por los integrantes del equipo de salud mental del Policlínico "Ernesto Guevara de la Serna" de Santiago de Cuba, desde enero hasta julio de 2013, a fin de lograr la deshabituación y mejorar la conducta ante los tóxicos. Se utilizaron las psicoterapias de grupo e individual, además de la sugestión como técnica afín a la hipnosis. En la casuística predominaron: el grupo de 14-16 años, con primacía del sexo masculino, los trastornos mentales como antecedentes patológicos personales (58,3 %), el consumo de sustancias como antecedente patológico familiar y los que consumían frecuentemente (66,6 %). Se logró la deshabituación en 2 de ellos, disminuyó el consumo en 7 y solo 3 se mantuvieron igual.

An intervention study by means of an integrated therapeutic system was carried out in 12 adolescent smokers and drinkers, belonging to Boniato village, attended by the mental health team of "Ernesto Guevara de la Serna" Polyclinic of Santiago de Cuba, from January to July 2013, in order to achieve detoxification and improve conduct related to toxic habits. Group and individual psychotherapies were used, and the suggestion as a technique related to hypnosis. The age group of 14-16 years, with predominance of the male sex, mental disorders as medical history (58.3%), use of substances as family history and those who consumed frequently (66.6%) predominated in the case material. Detoxification was achieved in 2 of them, consumption decreased in 7 and only 3 remained the same.

El ciclo de la violencia en consumidores de sustancias tóxicas / The cycle of violence in substance abusers

Se efectuó un estudio descriptivo de 46 pacientes consumidores de sustancias tóxicas, pertenecientes al área de salud del Policlínico Docente Ernesto Guevara de la Serna de Santiago de Cuba, de enero a julio del 2013, con vistas a valorar la influencia de los factores socioculturales en el desarrollo de la violencia y la adicción a las drogas. La totalidad de la serie fueron hombres, con predominio del grupo etario de 20-30 años y la escolaridad media, quienes procedían de familias con dificultad en sus relaciones y habían sido víctimas de violencia física, psicológica o sexual en su niñez o adolescencia. En cuanto a la victimización la habían realizado fundamentalmente los padres y maestros dentro del domicilio y la escuela, respectivamente; asimismo, la mayoría de los pacientes exhibían conductas violentas o antisociales que ejercían sobre algunos miembros de su familia y otras personas de su entorno, de modo que reproducían los comportamientos aprendidos en la infancia. El consumo de sustancias tóxicas se inició desde la adolescencia, para mantenerse prolongadamente durante varios años(AU)

A descriptive study was carried out in 46 patients, belonging to the health area of Ernesto Guevara de la Serna Teaching Polyclinic in Santiago de Cuba, from January to July 2013, to assess the influence of the sociocultural factors in the occurrence of violence and drug abuse. The entire series were men, with prevalence of the group aged 20-30 years and average education, who came from families with difficulties in their relationships and had been victims of physical, psychological or sexual violence in their childhood or adolescence. Parents and teachers were the main perpetrators at home and school, respectively. Also, most patients had violent and antisocial behaviors exerted on family members and other people of their environment, so they repeated behaviors learned in childhood. The substance abuse began in adolescence and has been held for several years(AU)

Factores de riesgo relacionados con la conducta suicida en la infancia y adolescencia / Risk factors related to suicidal behavior in childhood and adolescence

Se realizó un estudio observacional, descriptivo y transversal en el Hospital Infantil Norte Docente Dr Juan de la Cruz Martínez Maceira de la provincia de Santiago de Cuba en el 2010, a fin de describir los factores relacionados con la conducta suicida en 26 de 31 adolescentes de 11 a 17 años, atendidos en dicha institución durante ese período. Se halló que el grupo más afectado fue el de 14-15 años, con primacía del sexo femenino. Entre los factores de riesgo predominantes figuraron, por citar los principales en la casuística: los maltratos físicos y psicológicos como las humillaciones efectuadas por los propios padres; la falta de redes de apoyo familiar en la mayoría de ellos; la ausencia de solución de sus problemas; la ingestión de medicamentos para suicidarse, fundamentalmente psicofármacos, así como la depresión y el consumo de alcohol como antecedentes patológicos familiares(AU)

An observational, descriptive and cross sectional study was carried out in Dr Juan de la Cruz Martínez Maceira Teaching Northern Pediatric Hospital from Santiago de Cuba province in 2010, in order to describe the factors related to the suicidal behavior in 26 of 31 adolescents from 11 to 17 years, assisted in this institution during that period. It was found that the most affected group was that of 14-15 years, with prevalence of the female sex. Among the predominant risk factors there were, as the main ones in the case material: the physical and psychological abuses as the humiliations carried out by parents; the lack of family support groups in most of them; the absence of solution to their problems; the drugs ingestion to commit suicide, fundamentally psychodrugs, as well as depression and the alcohol consumption as family pathological history(AU)

Factores de riesgo relacionados con la conducta suicida en la infancia y adolescencia / Risk factors related to suicidal behavior in childhood and adolescence

Se realizó un estudio observacional, descriptivo y transversal en el Hospital Infantil Norte Docente "Dr. Juan de la Cruz Martínez Maceira" de la provincia de Santiago de Cuba en el 2010, a fin de describir los factores relacionados con la conducta suicida en 26 de 31 adolescentes de 11 a 17 años, atendidos en dicha institución durante ese período. Se halló que el grupo más afectado fue el de 14-15 años, con primacía del sexo femenino. Entre los factores de riesgo predominantes figuraron, por citar los principales en la casuística: los maltratos físicos y psicológicos como las humillaciones efectuadas por los propios padres; la falta de redes de apoyo familiar en la mayoría de ellos; la ausencia de solución de sus problemas; la ingestión de medicamentos para suicidarse, fundamentalmente psicofármacos, así como la depresión y el consumo de alcohol como antecedentes patológicos familiares.

An observational, descriptive and cross sectional study was carried out in "Dr. Juan de la Cruz Martínez Maceira" Teaching Northern Pediatric Hospital from Santiago de Cuba province in 2010, in order to describe the factors related to the suicidal behavior in 26 of 31 adolescents from 11 to 17 years, assisted in this institution during that period. It was found that the most affected group was that of 14-15 years, with prevalence of the female sex. Among the predominant risk factors there were, as the main ones in the case material: the physical and psychological abuses as the humiliations carried out by parents; the lack of family support groups in most of them; the absence of solution to their problems; the drugs ingestion to commit suicide, fundamentally psychodrugs, as well as depression and the alcohol consumption as family pathological history.

El ciclo de la violencia en consumidores de sustancias tóxicas / The cycle of violence in substance abusers

Se efectuó un estudio descriptivo de 46 pacientes consumidores de sustancias tóxicas, pertenecientes al área de salud del Policlínico Docente "Ernesto Guevara de la Serna" de Santiago de Cuba, de enero a julio del 2013, con vistas a valorar la influencia de los factores socioculturales en el desarrollo de la violencia y la adicción a las drogas. La totalidad de la serie fueron hombres, con predominio del grupo etario de 20-30 años y la escolaridad media, quienes procedían de familias con dificultad en sus relaciones y habían sido víctimas de violencia física, psicológica o sexual en su niñez o adolescencia. En cuanto a la victimización la habían realizado fundamentalmente los padres y maestros dentro del domicilio y la escuela, respectivamente; asimismo, la mayoría de los pacientes exhibían conductas violentas o antisociales que ejercían sobre algunos miembros de su familia y otras personas de su entorno, de modo que reproducían los comportamientos aprendidos en la infancia. El consumo de sustancias tóxicas se inició desde la adolescencia, para mantenerse prolongadamente durante varios años.

A descriptive study was carried out in 46 patients, belonging to the health area of "Ernesto Guevara de la Serna" Teaching Polyclinic in Santiago de Cuba, from January to July 2013, to assess the influence of the sociocultural factors in the occurrence of violence and drug abuse. The entire series were men, with prevalence of the group aged 20-30 years and average education, who came from families with difficulties in their relationships and had been victims of physical, psychological or sexual violence in their childhood or adolescence. Parents and teachers were the main perpetrators at home and school, respectively. Also, most patients had violent and antisocial behaviors exerted on family members and other people of their environment, so they repeated behaviors learned in childhood. The substance abuse began in adolescence and has been held for several years.

Information theoretically secure, enhanced Johnson noise based key distribution over the smart grid with switched filters.

We introduce a protocol with a reconfigurable filter system to create non-overlapping single loops in the smart power grid for the realization of the Kirchhoff-Law-Johnson-(like)-Noise secure key distribution system. The protocol is valid for one-dimensional radial networks (chain-like power line) which are typical of the electricity distribution network between the utility and the customer. The speed of the protocol (the number of steps needed) versus grid size is analyzed. When properly generalized, such a system has the potential to achieve unconditionally secure key distribution over the smart power grid of arbitrary geometrical dimensions.