Effect of COVID-19 pandemic on utilisation of community-based mental health care in North-East of Italy: A psychiatric case register study.

AIMS: WHO declared that mental health care should be considered one essential health service to be maintained during the coronavirus disease 2019 (COVID-19) pandemic. This study aims to describe the effect of lockdown and restrictions due to the COVID-19 pandemic in Italy on mental health services' utilisation, by considering psychiatric diagnoses and type of mental health contacts. METHODS: The study was conducted in the Verona catchment area, located in the Veneto region (northeastern Italy). For each patient, mental health contacts were grouped into: (1) outpatient care, (2) social and supportive interventions, (3) rehabilitation interventions, (4) multi-professional assessments, (5) day care. A 'difference in differences' approach was used: difference in the number of contacts between 2019 and 2020 on the weeks of lockdown and intermediate restrictions was compared with the same difference in weeks of no or reduced restrictions, and such difference was interpreted as the effect of restrictions. Both a global regression on all contacts and separate regressions for each type of service were performed and Incidence Rate Ratios (IRRs) were calculated. RESULTS: In 2020, a significant reduction in the number of patients who had mental health contacts was found, both overall and for most of the patients' characteristics considered (except for people aged 18-24 years for foreign-born population and for those with a diagnosis of schizophrenia. Moreover, in 2020 mental health contacts had a reduction of 57 096 (-33.9%) with respect to 2019; such difference remained significant across the various type of contacts considered, with rehabilitation interventions and day care showing the greatest reduction. Negative Binomial regressions displayed a statistically significant effect of lockdown, but not of intermediate restrictions, in terms of reduction in the number of contacts. The lockdown period was responsible of a 32.7% reduction (IRR 0.673; p-value <0.001) in the overall number of contacts. All type of mental health contacts showed a reduction ascribable to the lockdown, except social and supportive interventions. CONCLUSIONS: Despite the access to community mental health care during the pandemic was overall reduced, the mental health system in the Verona catchment area was able to maintain support for more vulnerable and severely ill patients, by providing continuity of care and day-by-day support through social and supportive interventions.

Equilibrium and nonequilibrium description of negative temperature states in a one-dimensional lattice using a wave kinetic approach.

We predict negative temperature states in the discrete nonlinear Schödinger (DNLS) equation as exact solutions of the associated wave kinetic equation. Within the wave kinetic approach, we define an entropy that results monotonic in time and reaches a stationary state, that is consistent with classical equilibrium statistical mechanics. We also perform a detailed analysis of the fluctuations of the actions at fixed wave numbers around their mean values. We give evidence that such fluctuations relax to their equilibrium behavior on a shorter timescale than the one needed for the spectrum to reach the equilibrium state. Numerical simulations of the DNLS equation are shown to be in agreement with our theoretical results. The key ingredient for observing negative temperatures in lattices characterized by two invariants is the boundedness of the dispersion relation.

Asking questions during breast cancer consultations: does being alone or being accompanied make a difference?

PURPOSE: Companions often accompany patients to cancer consultations. The number of questions asked by patients and companions is an indicator of their active participation. The present study aims to provide first descriptive evidence on the characteristics of unaccompanied and accompanied Italian breast cancer patients that attend the first consultation after surgery and to analyse companions contribution to the type and quantity of questions asked during the consultation. METHOD: Seventy consultations of female patients with breast cancer were audio taped. Questions were transcribed and coded by content. Companion's questions were also classified in terms of function. Socio-demographic and clinical data, patients' role preference and confidence in decision making measures were gathered for each patient. Post consultation satisfaction with decision and the perceived level of shared decision making were collected either for the patient and the companion. RESULTS: 69% of patients were accompanied, usually by one close family member, either husband or adult child. Non employed or retired patients and those with a preference for passive role in decision making were more likely to be accompanied. Unaccompanied patients and accompanied patients had comparable levels of anxiety, emotional distress and depression and were equally active in asking questions. These levels were far greater than those reported for other cancer patients in the literature. Companions did not increase significantly the number of questions per consultation. CONCLUSION: Accompanied and non accompanied patients differed more in socio-demographic than clinical characteristics. Companions sustained the patient and shared information without reducing the level of patient involvement.

Formación médica continuada basada en Internet. Presentación de la primera experiencia de la Sociedad Española de Medicina Interna / Internet-based Continuing Medical Education. Presentation of the first experience of the Spanish Society of Internal Medicine

Este documento presenta la primera experiencia de la Sociedad Española de Medicina Interna en el desarrollo de un programa de formación médica continuada basado en Internet para los miembros de la sociedad, acreditado por el Ministerio de Sanidad y la Universidad Autónoma de Barcelona, y financiado por el Grupo Menarini SA. Los resultados académicos y el grado de satisfacción de los participantes en este curso han sido muy elevados, tanto por lo que respecta a los contenidos científicos como al entorno virtual de aprendizaje. Esta experiencia demuestra que la formación médica continuada basada en Internet es un campo de gran futuro y con una buena aceptación por parte de los médicos participantes, y que las sociedades científicas, con la colaboración de otras instituciones y empresas, pueden liderar programas de formación médica continuada no presencial especialmente dirigidos y adaptados a sus afiliados(AU)

This paper presents the first experience of the Spanish Society of Internal Medicine in the development of an Internet-based Continuing Medical Education program for Society members, accredited by the Health Ministry and the Autonomous University of Barcelona, and funded by the Menarini Group SA. Academic performance and satisfaction of participants in this course have been very satisfactory, both with respect to scientific content and the virtual learning environment. This experience shows that Internet-based continuing medical education is a field with a great future that is well accepted by participating physicians, and that the scientific societies, with the collaboration of other institutions and companies, can lead Internet-based Continuing Medical Education programs especially designed and tailored to their members(AU)

[Internet-based Continuing Medical Education. Presentation of the first experience of the Spanish Society of Internal Medicine]. / Formación médica continuada basada en Internet. Presentación de la primera experiencia de la Sociedad Española de Medicina Interna.

This paper presents the first experience of the Spanish Society of Internal Medicine in the development of an Internet-based Continuing Medical Education program for Society members, accredited by the Health Ministry and the Autonomous University of Barcelona, and funded by the Menarini Group SA. Academic performance and satisfaction of participants in this course have been very satisfactory, both with respect to scientific content and the virtual learning environment. This experience shows that Internet-based continuing medical education is a field with a great future that is well accepted by participating physicians, and that the scientific societies, with the collaboration of other institutions and companies, can lead Internet-based Continuing Medical Education programs especially designed and tailored to their members.

In vivo and in vitro pharmacological characterization of SVT-40776, a novel M3 muscarinic receptor antagonist, for the treatment of overactive bladder.

BACKGROUND AND PURPOSE: Highly selective M(3) muscarinic receptor antagonists may represent a better treatment for overactive bladder syndrome, diminishing side effects. Cardiac side effects of non-selective antimuscarinics have been associated with activity at M(2) receptors as these receptors are mainly responsible for muscarinic receptor-dependent bradycardia. We have investigated a novel antimuscarinic, SVT-40776, highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). This study reports the functional activity of SVT-40776 in the bladder, relative to its activity in atria. EXPERIMENTAL APPROACH: In vitro and ex vivo (oral dosing) inhibition of mouse detrusor and atrial contractile responses to carbachol were used to study the functional activity of SVT-40776. The in vivo efficacy of SVT-40776 was characterized by suppression of isovolumetric spontaneous bladder contractions in anaesthetized guinea pigs after intravenous administration. KEY RESULTS: SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold). In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure. CONCLUSIONS AND IMPLICATIONS: SVT-40776 is a potent inhibitor of M(3) receptor-related detrusor contractile activity. The absence of effects on isolated atria preparations represents an interesting characteristic and suggests that SVT-40776 may lack unwanted cardiac effects; a feature especially relevant in a compound intended to treat mainly elderly patients.

[Epidemiology of work-related diseases in ULSS 12 Venice (Italy)]. / Epidemiologia delle malattie professionali nella ULSS 12 Veneziana.

In Veneto, like in Italy, in the last years the course of the professional diseases shown a trend in reduction. This trend has had to the difficulty to recognize the professional aetiology of multifactorial diseases. In the Venice the analysis of the course of the professional diseases in last the 4-5 years has demonstrated an increase of the communications of diseases from the doctors who operate in hospital to the SPISAL for the active search for pathologies asbestos and CVM correlated; moreover it has been a reduction of the hearing loss from noise from 2000 and it has been increment of cancer of lung and mesothelioma from 2001. Emergent diseases, like the allergy, the back diseases and those tied to the organizational constriction, are sottostimate. They have been a collaboration with the doctors of hospital, the doctors of factories, the INAIL and the court.

The statistical distribution of wrist movements during sleep.

The purpose of this work was to describe the basic statistical properties of the process of production of movements measured with a wrist actimeter, along a complete sleep period in normal human subjects. Two distinct types of random magnitudes were considered to analyze the data, the times between successive groups of movements and the number of movements at each fixed time (1 min) measurement epoch. Suitable probabilistic models for the two variates were chosen, fitting theoretical distribution functions to the observed data. It is concluded that interval data fit a one-parameter exponential distribution, while the number of movements fit a two-parameter negative binomial distribution. The estimated values of these parameters, besides being necessary to perform further statistical analysis, are a measure of the intensity and frequency of the movements. Finally the relationship between polysomnography measures and the elicited parameters was studied.

Effect of locally infused 2-chloroadenosine, an A1 receptor agonist, on spontaneous and evoked dopamine release in rat neostriatum.

Adenosine has been shown to inhibit dopamine release from striatal slices and synaptosomes. Recently, a direct interaction between the adenosine A2 receptor and dopamine D2 receptor has been provided. Activation of striatal adenosine A1 receptors is known to partially inhibit the release of dopamine (DA), but some aspects of this mechanism remain unclear. We have studied the participation of adenosine A1 receptors in the control of DA release 'in vivo' in awake, freely moving rats using microdialysis. To this end, the effects of 2-chloroadenosine (2-CADO), a non-metabolizable adenosine A1 receptor agonist, were studied on basal and stimulated striatal DA release. Basal levels were found to be slightly decreased by a maximal concentration of 2-CADO without any changes in DA metabolites. Haloperidol stimulated DA release was fully counteracted by 2-CADO. However, high K+ (100 mM) or (+)-amphetamine stimulated DA release was not altered by 2-CADO. Altogether, these data suggest that adenosine acting through A1 receptors possibly localized on striatal dopaminergic nerve terminals can block an induced D2 receptor blockade, but not the releasing effects caused by (+)-amphetamine and high K+ concentration. It is postulated that the increase in DA release by haloperidol is mainly due to an increased firing rate of the DA neurons and that A1 receptor activation can block the DA release observed in response to the action potential activation of DA nerve terminals.

Spirocerca lupi induced acute myelomalacia in the dog. A case report

Cäo macho, sem raça definida, de 3 anos de idade, foi atendido no Serviço de Neurologia por apresentar paraplegia de início súbito. Ao exame clínico-neurológico constatou-se uma síndrome medular toracolombar estando os membros pélvicos com paralisia espástica e com ausência de sensibilidade dolorosa profunda. Enquanto os exames radiográficos näo evidenciavam nenhuma anormalidade, as alteraçöes do líquor indicavam necrose ou hemorragia medular. O RIFI para Toxoplasmose foi de 1:1024. O exame bacterológico do líquor foi negativo. Devido à falta de resposta ao tratamento, o animal foi sacrificado. Na necrópsia encontraram-se hemorragias no segmento medular compreendido entre T8-T11. No exame histopatológico constatou-se a presença de um exemplar fêmea imaturo de Spirocerca lupi no tecido nervoso causando mielomalácia hemorrágica e consequentemente o quadro de paraplegia

Effect of acute administration of the 5-HT1A receptor ligand, lesopitron, on rat cortical 5-HT and dopamine turnover.

1. The involvement of presynaptic 5-hydroxytryptamine1A (5-HT1A) autoreceptors in the anxiolytic-like properties of lesopitron (E-4424) (2-(4-[4-(4-chloro-1-pyrazolyl)butyl]-1- piperazinyl)pyrimidine) was studied. Brain microdialysis was used to examine the effect of the drug on the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex of awake, freely moving rats. Moreover, extracellular cortical 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also studied to assess the possible participation of dopaminergic systems. 2. Lesopitron administered at a dose which induces anxiolytic behavior in rats (30 micrograms kg-1, i.p.) markedly reduced 5-HT levels (to 45% of the basal value) in cortical perfusates, having no effect on 5-HIAA, DOPAC and HVA. The effects of lesopitron were compared with those produced by the anxiolytic, and structurally related compound, buspirone. 3. Buspirone administered at a dose inducing anxiolytic-like effects in rats (5 mg kg-1, i.p.) produced a marked decrease in cortical 5-HT levels (to 20% of the basal value), but in contrast to lesopitron, buspirone produced a pronounced increase in cortical DOPAC (to 300% of the basal value) and HVA (to 400% of the basal value) levels. Buspirone administered at a low dose (30 micrograms kg-1, i.p.) was unable to affect cortical 5-HT levels. 4. To test the hypothesis that the 5-HT decreasing effect of lesopitron could be due to 5-HT1A autoreceptor (somatodendritic)-mediated inhibition of 5-HT neurotransmission, lesopitron was administered locally into the raphe nuclei. Intraraphe administration of 10 micro M lesopitron caused a decrease incortical 5-HT levels (the effect being of the same order as that obtained after systemic injection), with no effect on 5-HIAA, DOPAC and HVA. Raphe 5-HT extracellular levels were not modified afterintraraphe administration of lesopitron, indicating the absence of 5-HT reuptake blocking properties.5 We concluded that lesopitron, at an anxiolytic dose produced a marked inhibition of 5-HT release in the frontal cortex of awake, freely moving rats. This effect was observed after systemic administration as well as after intraraphe administration of the drug, suggesting an agonistic action at raphe 5-HTIA autoreceptors controlling 5-HT release in the projecting areas. In contrast to buspirone, lesopitrontreatment had no effect on cortical DOPAC or HVA levels.

Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol. A microdialysis study.

Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered.

Effect of age and cinnarizine treatment on brain dopamine receptors.

The density and distribution of dopamine D1 and D2 receptors visualized by in vitro autoradiography were investigated in adult and senescent BL C57 mice. A significant decrease was observed in regions of the basal ganglia of senescent animals, which was more pronounced for the D1 subtype. Chronic treatment with cinnarizine, an organic Ca2+ channel antagonist, alters both D1 and D2 receptor densities, with a higher sensitivity of the D1 subtype. These results could indicate that the interactions between dopamine receptor subtypes may be necessary for the full expression of behavioral events mediated by the D2 receptors.

Kainic acid-mediated increase of preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone.

The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid-injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid-induced increase of preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids.

Stimulation of glutamate receptors increases expression of brain-derived neurotrophic factor mRNA in rat hippocampus.

The activation of neocortical glutamatergic neuronal afferents to the hippocampus as well as direct pharmacologic non-NMDA receptor activation within the hippocampus was shown to result in a dramatic increase in BDNF mRNA expression in granule cells of the dentate gyrus and throughout the pyramidal layer, especially in CA1. Less pronounced effects were also seen for NGF mRNA. These results indicate that expression of BDNF and NGF in the brain is regulated by neuronal activity and glutamate receptor stimulation. This opens up the possibility that the increased levels of these factors seen after excitotoxic brain damage may have a protective role during such brain damage.

Activation of basal forebrain cholinergic neurons differentially regulates brain-derived neurotrophic factor mRNA expression in different projection areas.

Afferent cholinergic pathways from the basal forebrain were activated by injections of the glutamate analog quisqualate either into the nucleus basalis or into the medial septal nucleus. Nucleus basalis injections had no effect on the expression of brain-derived neurotrophic factor (BDNF) mRNA in its neocortical projection areas as measured by in situ hybridization. In contrast, 7 h after an injection into the septum the level of BDNF mRNA increased 3- to 5-fold in the dentate gyrus, throughout CA1 to CA3 in the hippocampus and in the piriform cortex.

Identification of guanine and adenine nucleotides as activators of glucose-1,6-bisphosphatase activity from rat skeletal muscle.

Glucose-1,6-bisphosphatase activity in rat skeletal muscle extracts was lost after exhaustive dialysis or precipitation with ammonium sulfate. Most of the original activity was recovered when the boiled extract was added to the ammonium sulfate precipitate. Qualitative analysis of the boiled extract revealed that the activator was either a nucleoside or a nucleotide. The results show that at concentrations between 0.05 and 1 mM, only guanine and adenosine derivatives are effective as activators, the former being more powerful. However, only guanosine, ADP, and AMP have an activating effect at the concentrations found in the boiled extract. The results of assays in vitro suggest that adenine nucleotides could be physiological modulators of glucose-1,6-bisphosphatase activity during muscle contraction.

Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain.

In situ hybridization and Northern blots were used to study expression of mRNAs for members of the nerve growth factor family in the rat brain following an excitatory stimulus. One hour after a unilateral needle insertion or saline injection into the dorsal hippocampus, the level of brain-derived neurotrophic factor (BDNF) mRNA increased markedly in granular neurons of the dentate gyrus and in the piriform cortex ipsilateral to the injection. The same treatment also increased the level of NGF mRNA in granular neurons of the ipsilateral dentate gyrus. The rapid increase in BDNF and NGF mRNA after a needle insertion or injection of saline was transient and preceded by an increase in c-fos mRNA in the same brain regions. In contrast to a needle insertion per se or a saline injection, 7 h after a unilateral injection of kainic acid into the dorsal hippocampus, the level of BDNF mRNA was dramatically increased in the ipsilateral hippocampus, as well as in the ipsilateral frontoparietal, piriform and perihinal cortex, the amygdaloid complex, claustrum, and ventromedial hypothalamus. A less pronounced increase was also seen in these brain areas on the contralateral side. Northern blots revealed that the level of BDNF mRNA increased 5- and 40-fold in the contra- and ipsilateral hippocampus, respectively, compared to sham-operated control animals. In contrast to BDNF and NGF, the level of hippocampus-derived neurotrophic factor/neurotrohin-3 (HDNF/NT-3) mRNA was not altered by either needle insertion or injection of saline or kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism.

The level of purines in the striatum of awake, freely moving rats was studied using microdialysis. The calculated extracellular concentration of adenosine and its metabolites inosine and hypoxanthine was very high immediately after implantation of the dialysis probe but decreased within 24 h to a level which remained stable for two days. Using in vitro calibration to determine the relative recovery of the dialysis probes we estimated resting levels in the striatal extracellular space to be 40, 110 and 580 nM, respectively. Inhibition of adenosine deaminase by deoxycoformycin produced a significant 1.4-fold increase in extracellular adenosine levels and a fall in inosine and hypoxanthine. A combination of three uptake blockers (dipyridamole, lidoflazine and nitrobenzylthioinosine), caused a 4.5-fold increase in extracellular adenosine levels without any change in inosine or hypoxanthine levels. After uptake inhibition deoxycoformycin did not have any significant effect. The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals. The high levels recorded during the first several hours after implantation may be artefactually high and reflect trauma. The results also show that adenosine levels can be altered in vivo by inhibitors of adenosine transport and adenosine deaminase. The present results indicate that the physiological adenosine level in striatal extracellular space is in the range 40-460 nM.

Dopamine D1 and D2 receptors visualized in MPTP treated C57 mice by in vitro autoradiography: lack of evidence of receptor modifications in parkinsonian mice.

The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on D1 and D2 dopamine receptors was assayed using in vitro quantitative autoradiography. D1 receptor subtype was labeled using 1 nM of 3H-SCH 23390 and D2 receptor subtype was labeled using 0.4 nM of 3H-spiroperidol. The results are compared to the effect of MPTP on the striatal levels of dopamine and its metabolites, in BL C57 mice. While 2 and 5 doses of MPTP 30 mg/kg/day intraperitoneally reduced the content of striatal dopamine and its metabolites, no modifications were detected in D2 receptor subtype in any cerebral area studied. However, D1 receptors were reduced in the substantia nigra 24 hr after the last of 2 doses, but not later. We suggest a compensatory mechanism of the surviving dopaminergic neurones as well as the participation of spare receptors. This would explain the lack of receptor modification after the lesion obtained as seen by the striatal reduction of dopamine and metabolites content, after MPTP administration.