Photoswitchable carbamazepine analogs for non-invasive neuroinhibition in vivo.

A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, which are used against epilepsy and neuropathic pain but cause systemic side effects. There is a need of drugs that inhibit nerve signals locally and on-demand without affecting other regions of the body. Photopharmacology aims to address this problem with light-activated drugs and localized illumination in the target organ. Here, we have developed photoswitchable derivatives of the widely prescribed antiseizure drug carbamazepine. For that purpose, we expanded our method of ortho azologization of tricyclic drugs to meta/para and to N-bridged diazocine. Our results validate the concept of ortho cryptoazologs (uniquely exemplified by Carbazopine-1) and bring to light Carbadiazocine (8), which can be photoswitched between 400-590 nm light (using violet LEDs and halogen lamps) and shows good drug-likeness and predicted safety. Both compounds display photoswitchable activity in vitro and in translucent zebrafish larvae. Carbadiazocine (8) also offers in vivo analgesic efficacy (mechanical and thermal stimuli) in a rat model of neuropathic pain and a simple and compelling treatment demonstration with non-invasive illumination.

Nerve Injury Triggers Time-dependent Activation of the Locus Coeruleus, Influencing Spontaneous Pain-like Behavior in Rats.

BACKGROUND: Dynamic changes in neuronal activity and in noradrenergic locus coeruleus (LC) projections have been proposed during the transition from acute to chronic pain. Thus, the authors explored the cellular cFos activity of the LC and its projections in conjunction with spontaneous pain-like behavior in neuropathic rats. METHODS: Tyrosine hydroxylase:Cre and wild-type Long-Evans rats, males and females, were subjected to chronic constriction injury (CCI) for 2 (short-term, CCI-ST) or 30 days (long-term, CCI-LT), evaluating cFos and Fluoro-Gold expression in the LC, and its projections to the spinal cord (SC) and rostral anterior cingulate cortex (rACC). These tests were carried out under basal conditions (unstimulated) and after noxious mechanical stimulation. LC activity was evaluated through chemogenetic and pharmacologic approaches, as were its projections, in association with spontaneous pain-like behaviors. RESULTS: CCI-ST enhanced basal cFos expression in the LC and in its projection to the SC, which increased further after noxious stimulation. Similar basal activation was found in the neurons projecting to the rACC, although this was not modified by stimulation. Strong basal cFos expression was found in CCI-LT, specifically in the projection to the rACC, which was again not modified by stimulation. No cFos expression was found in the CCI-LT LCipsilateral (ipsi)/contralateral (contra)→SC. Chemogenetics showed that CCI-ST is associated with greater spontaneous pain-like behavior when the LCipsi is blocked, or by selectively blocking the LCipsi→SC projection. Activation of the LCipsi or LCipsi/contra→SC dampened pain-like behavior. Moreover, Designer Receptor Exclusively Activated by Designer Drugs (DREADDs)-mediated inactivation of the CCI-ST LCipsi→rACC or CCI-LT LCipsi/contra→rACC pathway, or intra-rACC antagonism of α-adrenoreceptors, also dampens pain-like behavior. CONCLUSIONS: In the short term, activation of the LC after CCI attenuates spontaneous pain-like behaviors via projections to the SC while increasing nociception via projections to the rACC. In the long term, only the projections from the LC to the rACC contribute to modulate pain-like behaviors in this model.

Sexual differences in locus coeruleus neurons and related behavior in C57BL/6J mice.

BACKGROUND: In addition to social and cultural factors, sex differences in the central nervous system have a critical influence on behavior, although the neurobiology underlying these differences remains unclear. Interestingly, the Locus Coeruleus (LC), a noradrenergic nucleus that exhibits sexual dimorphism, integrates signals that are related to diverse activities, including emotions, cognition and pain. Therefore, we set-out to evaluate sex differences in behaviors related to LC nucleus, and subsequently, to assess the sex differences in LC morphology and function. METHODS: Female and male C57BL/6J mice were studied to explore the role of the LC in anxiety, depressive-like behavior, well-being, pain, and learning and memory. We also explored the number of noradrenergic LC cells, their somatodendritic volume, as well as the electrophysiological properties of LC neurons in each sex. RESULTS: While both male and female mice displayed similar depressive-like behavior, female mice exhibited more anxiety-related behaviors. Interestingly, females outperformed males in memory tasks that involved distinguishing objects with small differences and they also showed greater thermal pain sensitivity. Immunohistological analysis revealed that females had fewer noradrenergic cells yet they showed a larger dendritic volume than males. Patch clamp electrophysiology studies demonstrated that LC neurons in female mice had a lower capacitance and that they were more excitable than male LC neurons, albeit with similar action potential properties. CONCLUSIONS: Overall, this study provides new insights into the sex differences related to LC nucleus and associated behaviors, which may explain the heightened emotional arousal response observed in females.

Exploring sex differences in the brain is important to understand the impact of such differences in pathological conditions characterized by gender bias, as well as their therapeutic implications. In this manuscript, we examined sex differences in the mouse locus coeruleus (LC) and how this might affect related behaviours. The LC is a sexually dimorphic nucleus that integrates signals associated with attention, anxiety, stress, arousal, pain, memory and learning. Our findings reveal that female mice exhibit more intense anxiety-related behaviors but that they perform better than males in recognizing small differences between objects. Additionally, we found pronounced sex differences in the LC, which contained fewer noradrenergic cells in females, with a larger dendritic volume and displaying enhanced cell excitability. These differences in the LC, a nucleus that fulfils a pivotal role in stress and pain, could be important for understanding the higher prevalence of stress-related disorders in women, such as anxiety and depression, but also of chronic pain. Hence, it is clearly important to consider sex differences in both preclinical and clinical research studies that attempt to understand pathologies related to these phenomena.

The Role of the Locus Coeruleus in Pain and Associated Stress-Related Disorders.

The locus coeruleus (LC)-noradrenergic system is the main source of noradrenaline in the central nervous system and is involved intensively in modulating pain and stress-related disorders (e.g., major depressive disorder and anxiety) and in their comorbidity. However, the mechanisms involving the LC that underlie these effects have not been fully elucidated, in part owing to the technical difficulties inherent in exploring such a tiny nucleus. However, novel research tools are now available that have helped redefine the LC system, moving away from the traditional view of LC as a homogeneous structure that exerts a uniform influence on neural activity. Indeed, innovative techniques such as DREADDs (designer receptors exclusively activated by designer drugs) and optogenetics have demonstrated the functional heterogeneity of LC, and novel magnetic resonance imaging applications combined with pupillometry have opened the way to evaluate LC activity in vivo. This review aims to bring together the data available on the efferent activity of the LC-noradrenergic system in relation to pain and its comorbidity with anxiodepressive disorders. Acute pain triggers a robust LC stress response, producing spinal cord-mediated endogenous analgesia while promoting aversion, vigilance, and threat detection through its ascending efferents. However, this protective biological system fails in chronic pain, and LC activity produces pain facilitation, anxiety, increased aversive memory, and behavioral despair, acting at the medulla, prefrontal cortex, and amygdala levels. Thus, the activation/deactivation of specific LC projections contributes to different behavioral outcomes in the shift from acute to chronic pain.

Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus-dorsal reticular nucleus pathway.

ABSTRACT: The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsi inactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontra reduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsi or LCcontra reversed pain-induced depression 30 days after neuropathy. Long-term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontra but not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontra pathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontra pathway induced depressive-like behaviour in naïve animals, but it did not modify long-term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontra facilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.

Current Perspectives and Concerns Facing Hospital Evacuation: The Results of a Pilot Study and Literature Review.

OBJECTIVE: To analyze the evacuation preparedness of hospitals within the European Union (EU). METHOD: This study consisted of 2 steps. In the first step, a systematic review of the subject matter, according to the PRISMA flow diagram, was performed. Using Scopus (Elsevier, Amsterdam, Netherlands), PubMed (National Library of Medicine, Bethesda, MD), and Gothenburg University´s search engine, 11 questions were extracted from the review and were sent to representatives from 15 European Union (EU)- and non-EU countries. RESULTS: The findings indicate that there is neither a full preparedness nor a standard guideline for evacuation within the EU or other non-EU countries in this study. A major shortcoming revealed by this study is the lack of awareness of the untoward consequences of medical decision-making during an evacuation. Some countries did not respond to the questions due to the lack of relevant guidelines, instructions, or time. CONCLUSION: Hospitals are exposed to internal and external incidents and require an adequate evacuation plan. Despite many publications, reports, and conclusions on successful and unsuccessful evacuation, there is still no common guide for evacuation, and many hospitals lack the proper preparedness. There is a need for a multinational collaboration, specifically within the EU, to establish such an evacuation planning or guideline to be used mutually within the union and the international community.

A perspectiva dos enfermeiros dos cuidados de saúde primários face à emergência pré-hospitalar / The perspective of nurses in primary health care in the face of pre-hospital emergency

A emergência pré-hospitalar é uma temática atual e bastante debatida. Também a presença do enfermeiro na prestação de cuidados pré-hospitalares é considerada indispensável. Os enfermeiros dos Cuidados de Saúde Primários enfrentam por vezes situações de emergência nos seus serviços ou durante os domicílios que vão realizar. É sobre estes que nos vamos focar e procurar entender a importância que para eles reveste a emergência pré-hospitalar. É de extrema importância que estes enfermeiros tenham conhecimento atualizado da urgência/emergência e experiência prática nas diversas situações, para que se sintam à vontade nessas ocorrências e para que haja um apoio mútuo com a equipa multidisciplinar com que trabalham. Iremos estudar os enfermeiros pertencentes ao ACES Douro Sul, um ACES da zona Norte do país, que se encontram afastados dos grandes centros, uma vez que são estes profissionais os que mais necessitam de formação para poderem auxiliar os utentes sempre que estes se encontram em alguma situação de urgência/emergência. Para se ser enfermeiro pré-hospitalar é necessário um conjunto de requisitos que deverão ser tidos em conta antes de um profissional decidir optar por essa área pois é necessário um perfil profissional adequado. Com o presente Trabalho de Projeto pretende-se perceber como é que as equipas dos Cuidados de Saúde Primários se sentiam em relação à enfermagem pré-hospitalar e, se após doze anos do início da rede de requalificação das urgências se se consideram mais seguros e mais preparados para atender utentes urgentes. Para tal, foi feita uma pesquisa bibliográfica para a componente teórica que servirá de suporte para posterior realização de uma investigação.

Prehospital emergency is a current and widely discussed topic. Also, the presence of nurses in the provision of prehospital care is considered essential. Primary Health Care nurses sometimes face emergency situations in their services or during the home care support they provide. It is on these that we will focus and seek to understand the importance that for them the prehospital emergency has. It is extremely important that these nurses have urgency/emergency up-to-date knowledge and practical experience in various situations, so that they feel comfortable in these occurrences and so that there is mutual support with the multidisciplinary team with whom they work. We will study nurses who work for ACES Douro Sul, an ACES located in the northern part of the country, who are far from big cities, as these professionals are the ones who most need training to be able to assist patients whenever they are in a urgency/emergency situation. To be a prehospital nurse a set of requirements is necessary which must be taken into account before a professional decides to choose this area, as an appropriate professional profile is required. The aim of this Project Work is to understand how Primary Health Care teams felt about prehospital nursing and, if, 12 years after the beginning of the emergency redefinition network, they consider themselves more confident and well-prepared to attend urgent patients. To this end, a bibliographical research was carried out for the theoretical component which will support further investigation.

Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases.

Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer's disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

Selective deletion of Caspase-3 gene in the dopaminergic system exhibits autistic-like behaviour.

Apoptotic caspases are thought to play critical roles in elimination of excessive and non-functional synapses and removal of extra cells during early developmental stages. Hence, an impairment of this process may thus constitute a basis for numerous neurological and psychiatric diseases. This view is especially relevant for dopamine due to its pleiotropic roles in motor control, motivation and reward processing. Here, we have analysed the effect of caspase-3 depletion on the development of catecholaminergic neurons and performed a wide array of neurochemical, ultrastructural and behavioural assays. To achieve this, we performed selective deletion of the Casp3 gene in tyrosine hydroxylase (TH)-expressing cells using Cre-loxP-mediated recombination. Histological evaluation of most relevant catecholaminergic nuclei revealed the ventral mesencephalon as the most affected region. Stereological analysis demonstrated an increase in the number of TH-positive neurons in both the substantia nigra and ventral tegmental area along with enlarged volume of the ventral midbrain. Analysis of main innervating tissues revealed a rather contrasting profile. In striatum, basal extracellular levels and potassium-evoked DA release were significantly reduced in mice lacking Casp3, a clear indication of dopaminergic hypofunction in dopaminergic innervating tissues. This view was sustained by analysis of TH-labelled dopaminergic terminals by confocal and electron microscopy. Remarkably, at a behavioural level, Casp3-deficient mice exhibited impaired social interaction, restrictive interests and repetitive stereotypies, which are considered the core symptoms of autism spectrum disorder (ASD). Our study revitalizes the potential involvement of dopaminergic transmission in ASD and provides an excellent model to get further insights in ASD pathogenesis.

Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions.

BACKGROUND: One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. RESULTS: Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. CONCLUSIONS: We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.

Pain in neuropsychiatry: Insights from animal models.

Pain is the most common symptom reported in clinical practice, meaning that it is associated with many pathologies as either the origin or a consequence of other illnesses. Furthermore, pain is a complex emotional and sensorial experience, as the correspondence between pain and body damage varies considerably. While these issues are widely acknowledged in clinical pain research, until recently they have not been extensively considered when exploring animal models, important tools for understanding pain pathophysiology. Interestingly, chronic pain is currently considered a risk factor to suffer psychiatric disorders, mainly stress-related disorders like anxiety and depression. Conversely, pain appears to be altered in many psychiatric disorders, such as depression, anxiety and schizophrenia. Thus, pain and psychiatric disorders have been linked in epidemiological and clinical terms, although the neurobiological mechanisms involved in this pathological bidirectional relationship remain unclear. Here we review the evidence obtained from animal models about the co-morbidity of pain and psychiatric disorders, placing special emphasis on the different dimensions of pain.

Data regarding the effect of cannabis consumption on liver function in the prospective PAFIP cohort of first episode psychosis.

The presented article describes data from secondary analyses, related to the research article entitled "Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients" [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking.

Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients.

INTRODUCTION: Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS: A total of 390 patients were evaluated at baseline and after 3 years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS: At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F = 13.874; p < .001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2 = 7.97, p = .019). Longitudinally, patients maintaining cannabis consumption after 3 years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p = .022) and never-users (p = .016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS: Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.

Chemogenetic Silencing of the Locus Coeruleus-Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats.

BACKGROUND: Pain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear. METHODS: We characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs). RESULTS: Chronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory. CONCLUSIONS: Our results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.

Impact of the 2013 Floods on the Incidence of Malaria in Almanagil Locality, Gezira State, Sudan.

BACKGROUND: Heavy rain hit Sudan in August 2013 with subsequent flash floods in different parts of the country. This study investigated the impact of the flooding on incidence of malaria in Almanagil Locality in central Sudan. METHODS: This observational retrospective study compared malaria data sets during rainfall seasons in the Almanagil Locality in the year of flooding (2013) with those of corresponding rainfall seasons of previous two non-flood years (2011 and 2012). RESULTS: A marked increase of new malaria cases and incidence rate was observed in the 13 sentinel malaria notification sites in the locality  (IR increased from 6.09 per 100,000 person-days in 2011 [95 % CI: 5.93-6.26] and 6.48 in 2012 [95 % CI: 6.31-6.65] to 8.24 in 2013 [95 % CI: 8.05-8.43] ; P< 0.0001), with a peaking of the incidence rate in the under-5-years age group (IR for this age group jumped from 9.80 per 100,000 person-days in 2011 [95 % CI: 9.29-10.32] and 10.00 in 2012 [95 % CI: 9.52-10.49] to 15.02 in 2013 [95 % CI: 14.41-15.64]). A noticeable increase in the slide positivity rate (P< 0.0001) was observed in the 12-week period of 2013 (SPR = 20.86% [95 % CI: 20.40 -21.32%]) compared with the same periods in 2011 (SPR = 8.72% [95 % CI: 8.36 -9.08%]) and 2012 (SPR = 12.62% [95 % CI: 12.24 -13.01%]), with a more marked rise of the SPR in the under-5-year age group. Hospital data showed increase in both the inpatient and outpatient incidence proportions in the study period of 2013 compared to those of the years 2011 and 2012. Hospital OPD incidence proportion in 2013 was 19.7% (95% CI: 19.24-20.18%) compared to 12.85% (95% CI: 12.48-13.23%) in 2011, and 12.16% (95% CI: 11.82-12.51%) in 2012. The < 5 year old groups were responsible for the overall rise in the proportion of malaria cases in 2013 , particularly the < 1 year old group which more than doubled in the 2013 period compared to both 2011 and 2012 periods (Age-specific proportion of the outpatient malaria cases of the < 1 year old group in 2013 was19.5% [95% CI: 18.5-20.6%]  compared to 7.7% [95% CI: 6.9-8.6%] in 2011 and 8.1% [95% CI: 7.3-8.9%] in 2012. Incidence proportion of severe malaria cases (inpatients) increased to 22.5 % (95 % CI: 21.5 to 23.6 %) in the study period of 2013 compared to 19.8 % (95 % CI: 18.6 to 21.0 %) in 2011 and 18.4 % (95 % CI: 17.4 to 19.5) in 2012. The increase in the proportion of severe malaria cases was mainly due to a higher proportion of children < 5 years of age and especially to a higher proportion of children < 1 year of age. CONCLUSION: The study revealed a significant increase in the incidence rate of malaria in Almanagil Locality following the flash flood of August 2013. The flooding had the highest impact on the malaria incidence of the under-5-years age group, and particularly of the under-1-year age group.

Tecnologia móvel para coleta de dados de pesquisas em saúde / Mobile application for data collection in health research

Resumo Objetivo: Descrever o desenvolvimento de aplicativo de tecnologia móvel para coleta de dados em pesquisa de tempo e movimento dos profissionais de saúde do Programa Estratégia de Saúde da Família, na realização das intervenções/atividades de cuidado. Métodos: Pesquisa aplicada de produção tecnológica fundamentada no conceito de prototipagem e nas fases de definição, desenvolvimento e manutenção, para construção e validação de aplicativo do "instrumento de medida de carga de trabalho dos profissionais de saúde na atenção primária", para dispositivo móvel tablet Motorola® com sistema operacional Android® 3.2, com a finalidade de coletar dados em pesquisa de tempo e movimento, por meio da técnica de amostragem do trabalho e identificar a carga de trabalho de profissionais de saúde, lotados em unidades de saúde da família, localizadas nas cinco regiões geográficas do Brasil, consideradas de ótimo desempenho pelo Programa de Melhoria do Acesso e da Qualidade da Atenção Básica - ciclo 1. Resultados: O aplicativo potencializou a coleta de dados e facilitou as seguintes etapas: registro e armazenamento dos dados; manutenção da integridade da informação; transmissão e armazenamento dos dados; organização e processamento das informações e maior segurança na análise dos resultados. A transmissão e a extração dos dados foram realizadas diariamente, através da sincronização dos arquivos no Dropbox®. O aplicativo eletrônico foi utilizado durante as observações dos 418 profissionais de saúde das 27 unidades de saúde da família, no total foram registrados 85.398 observações de intervenções/atividades. Conclusão: O aplicativo possibilitou uma coleta de dados mais dinâmica; manteve a integridade da informação; auxiliou a transmissão e o armazenamento de dados; facilitou a organização e o processamento das informações e proporcionou maior segurança na análise dos resultados.

Abstract Objective: Describe the development of a mobile application for data collection in time and movement research with health professionals from the Family Health Strategy Program when conducting care interventions/activities. Methods: Applied research of technological production based on the concept of prototyping and the steps of definition, development, and maintenance, for the design and validation of the application: instrumento de medida de carga de trabalho dos profissionais de saúde na atenção primária (Workload measurement instrument for health professionals in primary care). This will be for a mobile Motorola® tablet with Android® 3.2 operating system, with the goal of collecting data for a time and movement study, using the work sampling technique, and identifying the workload of health professionals from family health units (FHUs) located in all five Brazilian geographic regions, presenting an excellent performance in the Primary Care Access and Quality Improvement Program - cycle 1. Results: The application intensified data collection and facilitated data recording and storage; data transmission; and data organization and processing; and ensured greater reliability in the analysis of results, maintaining data integrity in all these steps. Data transmission and extraction were performed on a daily basis, through file synchronization in Dropbox®. The mobile application was used during the observation of all 418 health professionals from the 27 family health units. In total 85,398 observations of interventions/activities were registered. Conclusion: The application allowed for more dynamic data collection; maintained data integrity; supported data transmission and storage; facilitated data organization and processing; and provided greater reliability in the analysis of results.

Carga de trabalho dos profissionais de saúde: instrumentos de medida segundo a Classificação das Intervenções de Enfermagem / Health professionals workload: measurement instruments according to the Nursing Interventions Classification

Introdução: Conhecer e medir a carga de trabalho dos profissionais de saúde pode contribuir para a gestão eficiente e eficaz das organizações de saúde, a carga de trabalho excessiva é a principal causa de estresse e insatisfação. Objetivo: Levantar e analisar as dissertações e teses referentes à distribuição da carga de trabalho dos profissionais de saúde, fundamentadas na Classificação das Intervenções de Enfermagem, desenvolvidas por participantes do grupo de pesquisa Gerenciamento de recursos humanos: conceitos, instrumentos e indicadores do processo de dimensionamento de pessoal, cadastrado no diretório do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Método: Estudo secundário tipo documental para identificar os instrumentos produzidos para medir a carga de trabalho, as intervenções/atividades realizadas, bem como a probabilidade de ocorrência e o percentual do tempo produtivo na jornada de trabalhadores profissionais de saúde. As fontes de dados foram dissertações e teses desenvolvidas pelos participantes do grupo de pesquisa disponíveis no banco de TESES-USP e DEDALUS. Resultados: Foram selecionados dezessete estudos nos quais foram construídos dezessete instrumentos de medida da carga de trabalho para profissionais de saúde sendo: 11,7% enfermeiros, 76,5% enfermeiros e técnicos/auxiliares de enfermagem, 5,9% assistente técnico administrativo e 5,9% nutricionista clínico. Os instrumentos foram aplicados nas unidades de alojamento conjunto, ambulatório de especialidades de oncologia e hematologia, centro cirúrgico de oncologia, centro de diagnóstico por imagem, clínica cirúrgica, clínica médica, emergência, serviço de nutrição, sala de recuperação pós-anestésica, unidade de internação pediátrica, unidades de terapias intensivas: adulto, pediátrica e neonatal; unidade de saúde da família. Os instrumentos apresentaram 192 intervenções de cuidado direto, 75 com frequência 1% e 80 intervenções de cuidado indireto, 39 com frequência 1%. As intervenções com maior frequência, no conjunto das unidades, foram Documentação, Administração de medicamentos, Passagem de plantão. O tempo produtivo dos profissionais na jornada ficou distribuído entre intervenções de cuidado direto e indireto e atividades associadas ao trabalho. Conclusões: Os instrumentos elaborados e aplicados evidenciaram as intervenções/atividades essenciais em cada unidade estudada e por categoria profissional que mais contribuem na medida da carga de trabalho e no tempo produtivo, mostrando ser importante estratégia gerencial para reorganizar os processos de trabalho.

Introduction: Knowing and measuring the workload of health professionals can contribute to the efficient and effective management of health organizations; excessive workload is the main cause of stress and dissatisfaction. Objectives: Analyze the dissertations and theses related to the distribution of the workload of health professionals, based on the Classification of Nursing Interventions, developed by participants of the research group "Human resources management: concepts, instruments and indicators of the nursing staff process registered in the directory of the National Council of Scientific and Technological Development (CNPq). Methods: Documentary study secondary type to identify the instruments produced to measure the workload, was performed, the interventions / activities performed, the interventions / activities performed, as well as the probability of occurrence and the percentage of productive time in the workday of health professionals. The data sources were dissertations and theses, developed by the research group participants available at the thesis base USP and DEDALUS. Results: Were selected seventeen studies were carried out in which 17 workload measurement instruments were constructed for health professionals: 11.7% nurses, 76.5% nurses and technicians/Nursing assistants, 5.9% administrative assistant and 5, 9% clinical nutritionist. They were applied in pediatric areas, medical clinic, surgical clinic, emergency, rooming-in, surgical center, units of intensive therapies: adult, pediatric and neonatal, oncology and hematology outpatient clinic, diagnostic imaging center; family health unit and nutrition service. The instruments presented 192 direct care interventions, 75 with 1% frequency and 80 indirect care interventions, 39 with frequency 1%. The most frequent interventions, in the units as a whole, were Documentation, Medication Administration, Shift work. The productive time of the professionals on the journey was distributed between direct and indirect care interventions and work-related activities. Conclusions: The instruments elaborated and applied showed the essential interventions / activities in each unit studied and by professional category that contribute the most to the work load and productive time, showing that it is an important managerial strategy to reorganize work processes.

Updating stored memory requires adult hippocampal neurogenesis.

Adult hippocampal neurogenesis appears to influence hippocampal functions, such as memory formation for example. While adult hippocampal neurogenesis is known to be involved in hippocampal-dependent learning and consolidation processes, the role of such immature neurons in memory reconsolidation, a process involved in the modification of stored memories, remains unclear. Here, using a novel fast X-ray ablation protocol to deplete neurogenic cells, we have found that adult hippocampal neurogenesis is required to update object recognition stored memory more than to reinforce it. Indeed, we show that immature neurons were selectively recruited to hippocampal circuits during the updating of stored information. Thus, our data demonstrate a new role for neurogenesis in cognitive processes, adult hippocampal neurogenesis being required for the updating of stored OR memories. These findings suggest that manipulating adult neurogenesis may have a therapeutic application in conditions associated with traumatic stored memory, for example.

Absenteísmo do pessoal de enfermagem: decisões e ações de enfermeiros gerentes / Absentismo del personal de enfermeira: decisiones y acciones de las enfermeiras gestoras / Absenteeism of nursing staff: decisions and actions of nurse managers

RESUMO Objetivo Mensurar o absenteísmo dos enfermeiros técnicos/auxiliares de enfermagem em três instituições hospitalares e conhecer possíveis decisões gerenciais de enfermeiros gerentes frente a este evento. Método Quantiqualitativo, sendo que, na etapa quantitativa mediu as taxas mensais, média anual e taxa geral de absenteísmo dos enfermeiros e técnicos/auxiliares de enfermagem de 12 unidades de serviço dos hospitais, durante 12 meses, segundo a equação proposta pelo NAGEH. Na etapa qualitativa foram realizadas entrevistas com as 12 enfermeiras gerentes das 12 unidades. Resultados A etapa quantitativa mostra diferenças importantes em cada instituição e entre instituições com diversas taxas mensais acima da taxa mensal máxima preconizada pelo COFEN de 6,7%. Na etapa qualitativa foram resgatadas as decisões de impacto positivo, por elas tomadas, considerando o relacionamento com chefia, o diálogo, e o atendimento das demandas de ordem física e emocional dos profissionais como fatores importantes. Conclusão O absenteísmo mostrou-se como um evento presente no cotidiano do gerenciamento do pessoal de enfermagem, pois apresentou variações nos diferentes meses do ano e nas diferentes unidades de serviço sendo possível classificá-las frente à maior ou menor problemática, além disso, mostrou o adoecimento do trabalhador, insatisfação com as condições institucionais e o relacionamento interpessoal inadequado, o que orienta para decisões gerenciais próprias a realidade.

RESUMEN Objetivo Mensurar el absentismo de los enfermeros técnicos/asistentes de enfermería en tres instituciones hospitalarias y conocer las posibles decisiones de gestión de los enfermeros gestores frente a este evento. Método Estudios cuantitativos y cualitativos, siendo que, en la fase cuantitativa mide las tasas mensuales, y promedio anual tasa general de absentismo del personal de enfermería y técnicos/asistentes de enfermería de 12 unidades de servicio de los hospitales durante 12 meses, de acuerdo con la ecuación propuesta por NAGEH. En la etapa cualitativa fueron realizadas entrevistas con as 12 enfermeras gestoras de las 12 unidades. Resultados La etapa cuantitativa muestra diferencias importantes en cada institución y entre instituciones con distintas tasas mensuales por encima de la tasa máxima mensual abogada por el COFEN de 6,7%. En la etapa cualitativa fueron rescatadas las decisiones de impacto positivo, por ellas tomadas, considerando el relacionamiento con los superiores, el diálogo y el atendimiento de las demandas de orden física y emocional de los profesionales como factores importantes. Conclusión el absentismo resultó como un evento presente en el cotidiano del gerenciamiento del personal de enfermería, pues presentó variaciones en los distintos meses del año y en las distintas unidades de servicio siendo posible clasificar frente a la mayor o menor problemáticas, además, mostró la enfermedad del trabajador, insatisfacción con las condiciones institucionales y el relacionamiento interpersonal inadecuado, lo que orienta para decisiones gestoras propias a la realidad.

ABSTRACT Objective Measure absenteeism among nurses and nursing technicians/aides in three hospitals and explore possible management decisions by nursing managers to deal with it. Method Quantitative, qualitative study. In the qualitative stage, monthly rates, annual average and overall rates of absenteeism were measured among nurses and nursing technicians/aides from 12 service units in the hospitals, over 12 months, according to the equation proposed by the Support Center for Hospital Management (NAGEH - Núcleo de Apoio à Gestão Hospitalar). In the qualitative stage, 12 nursing managers from 12 units were interviewed. Results The quantitative stage revealed important differences in each institution and between institutions, with various monthly rates exceeding the monthly rate of 6.7% recommended by the Federal Council of Nursing (COFEN - Conselho Federal de Enfermagem). The qualitative stage examined positive impact decisions taken by these institutions, where relationships with managers, dialogue, and meeting the physical and emotional demands of professionals were considered important factors. Conclusion Absenteeism was a reality in day-to-day nursing staff management. It varied according to the month of the year and in different service units, and it was possible to classify these units according to the degree of the problem. In addition, the results showed that employee illness, dissatisfaction with institutional conditions, and inadequate interpersonal relationships were key factors, enabling management decisions based on each hospital's particular reality.