Coexisting with dependence and well-being: the results of a pilot study intervention on 75-99-year-old individuals.

BACKGROUND: The objective of this study is to design and implement an intervention program centered on preventing functional dependence. METHODS: A pre/post quasi-experimental (typical case) design study with a control group was conducted on a group of 75-90-year-old individuals with functional dependence (n = 59) at three nursing homes in Madrid (Spain). The intervention program consists of two types of activities developed simultaneously. Some focused on emotional well-being (nine 90-minute sessions, once per week), whereas others focused on improving participants' physical condition (two 30-minute sessions, twice per week). The simple randomized participants included 59 elderly individuals (Intervention Group = 30, Control Group = 29) (mean age 86.80) [SD, 5. 19]. RESULTS: Fifty-nine participants were analyzed. The results indicate that the program is effective in improving mood, lowering anxiety levels (d = 0.81), and increasing both self-esteem (d = 0.65) and the perception of self-efficacy (d = 1.04). There are improvements in systolic pressure and functional dependence levels are maintained. Linear simple regression (independent variable pre-Barthel) shows that the pre-intervention dependence level can predict self-esteem after the intervention. CONCLUSION: We have demonstrated that the program is innovative with regard to bio-psychosocial care in elderly individuals, is based on actual practice, and is effective in increasing both self-esteem and self-efficacy. These variables positively affect functional capabilities and delay functional dependence.

[Nirsevimab effectiveness against hospital admission for respiratory syncytial virus bronchiolitis in infants]. / Efectividad de nirsevimab en la prevención de los ingresos por bronquiolitis por virus respiratorio sincitial en lactantes.

OBJECTIVE: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. This season, a long half-life monoclonal antibody (Nirsevimab) is available to prevent this disease for all infants born from 1 April-30 September to 2023 and all those born during RSV season (October2023- March 2024). The aim of this study was to evaluate the impact of the implementation of this antibody on RSV admissions in a tertiary hospital. METHODS: Observational, retrospective and analytical study. All patients <6 months in October admitted for bronchiolitis at 2 time points were included: T1 or Pre-nirsevimab time: 1 September 2015-30 September 2023 and T2 or Nirsevimab time: 1 October-31 December 2023. Total admissions due to any cause of infants <6 months in the same period were used as the reference population. To assess the impact of the implementation of nirsevimab, we calculated the reduction in the percentage of admissions due to RSV with respect to total admissions in both periods, and also in the 2023-2024 season we calculated the double negative test to calculate the effectiveness of the intervention (1-Odds ratio) x 100. RESULTS: In infants under 6 months of age, we found significant differences in the number of admissions for RSV bronchiolitis between the last season and the previous 7 seasons [574/1195 (48%) vs 6/138 (4.3%); p<0.01, RPI: 91%). In the 2023/2024 season, the effectiveness of nirsevimab in preventing admission for RSV bronchiolitis in children under 6 months of age was 85% (CI 95%: 32-97%). CONCLUSIONS: The implementation of nirsevimab has had an important impact on the number of hospital admissions for RSV bronchiolitis. There were no differences in the severity of bronchiolitis.

Comparative analysis of Met-enkephalin, galanin and GABA immunoreactivity in the developing trout preoptic-hypophyseal system.

We studied the organization of Met-enkephalin-containing cells and fibers in the developing preoptic-hypophyseal system of the brown trout (Salmo trutta fario) by immunohistochemistry and determined the relationship of these cells and fibers to the galaninergic and GABAergic systems. Met-enkephalin immunoreactivity was observed in cells in the preoptic area, the hypothalamus and the pituitary of late larvae. In the hypophysis, a few Met-enkephalin-containing cells were present in all divisions of the adenohypophysis, and some immunoreactive fibers were present in the interdigitations of the neural lobe with the proximal pars distalis. Concurrently, GABAergic fibers innervated the anterior and posterior neural lobe. Galanin cells coexisted with Met-enkephalin cells in neuronal groups of the preoptic-hypophyseal system. Galaninergic and GABAergic fibers innervated the preoptic and hypothalamic areas, but GABAergic fibers containing galanin were not observed. These results indicate that Met-enkephalin, galanin and GABA may modulate neuroendocrine activities in the preoptic area, hypothalamus and pituitary during the transition from larval to juvenile period. To better know how the development of the trout preoptic-hypophyseal system takes place, we studied the patterns of cell proliferation and expression of Pax6, a conserved transcription factor involved in the hypophysis development. Pax6 expressing cells and proliferating cells were present in the Rathke's pouch, the hypothalamus and the hypophysis of early larvae. In late larvae, Pax6 expression was no longer observed in these areas, and the density of proliferating cells largely decreased throughout development, although they remained in the hypophysis of late larvae and juveniles, suggesting that Pax6 might play an important role in the early regionalization of the pituitary in the trout.

Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature.

UNLABELLED: Harlequin syndrome (HS) is a rare autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is characterized by unilateral diminished sweating and flushing of the face even though after heat or prolonged exercise. It is typically acquired. Congenital cases only represent a 6% of all individuals with HS. All congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement. HS represents an uncommon autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration in facial appearance: ipsilateral denervated pale and dry half from the other intact red and moist half. CONCLUSION: We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.

Glycosylated phosducin-like protein long regulates opioid receptor function in mouse brain.

Phosducin (Phd), a protein that in retina regulates rhodopsin desensitization by controlling the activity of Gt beta gamma-dependent G-protein-coupled receptor kinases (GRKs), is present in very low levels in the CNS of mammals. However, this tissue contains proteins of related sequence and function. This paper reports the presence of N-glycosylated phosducin-like protein long (PhLP(L)) in all structures of mouse CNS, mainly in synaptic plasma membranes and associated with G beta subunits and 14-3-3 proteins. To analyze the role PhLP(L) in opioid receptor desensitization, its expression was reduced by the use of antisense oligodeoxynucleotides (ODNs). The antinociception induced by morphine, [D-Ala(2), N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO), beta-endorphin, [D-Ala(2)]deltorphin II, [D-Pen(2,5)]-enkephalin (DPDPE) or clonidine in the tail-flick test was reduced in PhLP(L)-knock-down mice. A single intracerebroventricular (icv)-ED(80) analgesic dose of morphine gave rise to acute tolerance that lasted for 4 days, but which was prevented or reversed by icv-injection of myristoylated (myr(+)) G(i2)alpha subunits. PhLP(L) knock-down brought about a myr(+)-G(i2)alpha subunit-insensitive acute tolerance to morphine that was still present after 8 days. It also diminished the specific binding of (125)I-Tyr(27)-beta-endorphin-(1-31) (human) to mouse periaqueductal gray matter membranes. After being exposed to chronic morphine treatment, post-dependent mice required about 10 days for complete recovery of morphine antinociception. The impairment of PhLP(L) extended this period beyond 17 days. It is concluded that PhLP(L) knock-down facilitates desensitization and uncoupling of opioid receptors.

Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice.

In mice whose Gi/o-protein function had been impaired by antisense 'knock-down' or pertussis toxin treatment, i.c.v. injection of myr+-Gi/o alpha subunits restored the effectiveness of beta-endorphin, morphine, DPDPE, clonidine and neurotensin to produce antinociception. Myr+-G alpha subunits of the class of G-proteins actually impaired were more effective than unlike but related myr+-G alpha subunits. Selectivity was noted in that only exogenous myr+-G alpha subunits affected (enhanced) the activity of agonists in G alpha-deficient signalling systems. This treatment had little effect on agonist potency when the impairment resided at the receptor level. The potential of the opioids, clonidine and R-PIA to increase G alpha-related in vitro hydrolysis of GTP was also re-established after injecting myr+-Gi2 alpha subunits into Gi2-knocked-down mice. Myr+-Gi2 alpha subunits pre-incubated with GTPgammaS or GDPbetaS before i.c.v. injection did not improve the activity of agonists in vivo (antinociception) or in vitro (regulation of low Km GTPase). After impairing the function of PKCbeta1 by antisense treatment or with the inhibitor H7, the effect of myr+-G alpha subunits on agonist potency was prevented. Electron microscope analysis showed the entry of gold-conjugated myr+-G alpha subunits into neural cells. These particles were found in the cytoplasm, associated with the plasma membranes of different neuronal processes and also in synaptic junctions. In cultured neurons and astrocytes myr+-Gi2 alpha-associated fluorescence was internalised in a dose-dependent manner and distributed in the plasma membrane and cytosol, as well as in nuclei of dividing astrocytes. Thus, G alpha subunits in CSF enter into neurons and functionally couple to the receptor-triggered signalling cascade. As G-proteins have been implicated in the pathophysiology of several neural disorders, this finding may be valuable in the therapy of such dysfunctions.

Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease.

At the beginning of the 1970s, different studies reported behavioural disturbances after the intracerebroventricular (icv) administration of 6-hydroxydopamine (6-OHDA) in the rat. Despite the fact that this neurotoxic agent degenerates brain dopaminergic (DA-) cells, its potential utility to produce a rat model of Parkinson's disease (PD) was never systematically studied because the aphagia and adipsia were often observed. In the present study, a procedure that induces a marked DA-cell degeneration that bypasses these and other undesirable complications of icv injection of 6-OHDA is reported. Lesioned animals (50-500 microg of 6-OHDA) showed a persistent motor syndrome composed of hypokinesia, purposeless chewing and catalepsy. The intensity of motor signs was dose-dependent, and recovered partially after administration of DA-receptor agonists, exposure to sensorial stimuli and stress, three procedures that reduce motor dysfunctions in Parkinson's disease (PD). Lesioned animals showed bilateral and symmetrical midbrain DA-cell degeneration with the highest cell-loss in A9 group (substantia nigra), followed by A8 (retrorubral field) and A10 (ventral tegmental area) groups. The similarity between the behavioural syndrome and the topographical profile of cell-loss after icv injection of 6-OHDA in rats and the clinical and neuropathological features of PD indicates that this may be a convenient animal model of PD particularly useful for checking in rats the possible efficacy of new anti-parkinsonian drugs on specific parameters of motor dysfunctions.

Tyrosine ingestion during rat pregnancy alters postnatal development of dopaminergic neurons in the offspring.

It has been previously reported that tyrosine ingestion by the mother rat during gestation modifies different behavioral patterns in the adult offspring. In the present study, the action of maternal mother tyrosine ingestion on the postnatal development of the dopaminergic system of the offspring was evaluated. The offspring of tyrosine-treated mothers showed a decrease in dopamine (DA) levels during the first 15 days of postnatal life and an increase in DA levels from day 30 to adulthood. The DOPAC level and the DOPAC/DA index were higher in the tyrosine group from postnatal life to adulthood. These differences reach statistical significance in both forebrain and mesencephalon. During adulthood the DA concentration in both s. nigra and ventral tegmental area were higher in the tyrosine group than in the control group. The behavioral postsynaptic response to a DA receptor agonist (apomorphine) was higher in the offspring of tyrosine treated rats than in the control group. These data suggest that the bioavailability of the DA precursor tyrosine during gestation may modify during postnatal life DA synapsis at both pre- and postsynaptic level.

Tryptophan ingestion by gestant mothers alters prolactin and luteinizing hormone release in the adult male offspring.

The effect of tryptophan administration to pregnant rats on the development of serotonergic systems and serotonin-related hormones in the offspring was studied. The male offspring of rats treated with tryptophan (200 mg/kg/day) during the second half of gestation showed a 4- to 7-fold increase in serum prolactin 40 and 70 days after birth and a 2-fold increase in serum luteinizing hormone 70 days after birth. The forebrain of adult offspring of tryptophan-treated rats showed an increase in serotonin and 5-hydroxyindoleacetic acid levels. Present data suggest that tryptophan regulates serotonergic differentiation during early development.

Use of selective antagonists and antisense oligonucleotides to evaluate the mechanisms of BUBU antinociception.

Evidence suggests that the antinociceptive effects of selective delta-opioid receptor agonists may involve an activation of the mu-receptor in some experimental conditions. The aim of this study was to clarify the receptors involved in the antinociceptive responses of the selective and systemically active delta-opioid receptor agonist Tyr-D-Ser-(O-tert-butyl)-Gly-Phe-Leu-Thr-(O-tert-butyl) (BUBU). The antinociception induced by systemic (i.v.) or central (i.c.v.) administration of BUBU was measured in the hot plate (jumping and paw lick latencies) and tail immersion tests in mice. In both tests, the responses were more intense when BUBU was administered by central route. The pre-treatment with the mu-opioid receptor antagonist cyprodime blocked the effects induced by central BUBU in the hot plate and tail immersion tests. The delta-opioid receptor antagonist naltrindole had no effect on BUBU-induced antinociception in the hot plate but decreased BUBU responses in the tail immersion test. Further evidence for this dual receptor action of BUBU was demonstrated by using antisense oligodeoxynucleotides. Thus, a reduction in central BUBU-induced antinociception was observed in the tail immersion test after the administration of antisense probes that selectively blocked the expression of mu- or delta-opioid receptors. These findings clearly indicate using a dual pharmacological and molecular approach that BUBU mediates its antinociceptive effects via activation of both mu- and delta-opioid receptors.

Nigrostriatal dopaminergic cell activity is under control by substantia nigra of the contralateral brain side: electrophysiological evidence.

The biochemical balance between right- and left-ascending DA systems is an essential factor to regulate behavioral lateralization. However, there is no electrophysiological evidence for the regulation of interhemispheric DA systems. In the present paper we report electrophysiological evidence supporting the hypothesis that the A9 DA cells are under control of the contralateral substantia nigra. The activity of more than 80% of the A9 cells recorded was affected by contralateral SN stimulation. This is a very high proportion because the previously reported response of A9 cells to ipsilateral caudate stimulation is proportionally lower. The potency of a stimulus, estimated as the number of action potentials induced or inhibited by each electrical stimulation of the contralateral substantia nigra or by the percentage of modification in the number of action potentials induced or inhibited in relation to the spontaneous potential expected, was also high. The response to the contralateral stimulation was complex. Fifty-four percent of all the DA cells studied showed more than a single response. Forty-four percent showed at least one stimulation and at least one inhibition. Because 1) the percentage of cells with at least one stimulation (70%) was higher than the percentage of cells with at least one inhibition (56%), and 2) the potency of stimulations was higher than the inhibition potency, the present data provide evidence that contralateral control of A9 cells is mainly excitatory. The percentage of cells activated by contralateral stimulation was high, between 30 ms and 220 ms and between 400 ms and 700 ms. The probability of inhibition was higher than the probability of activation between 10 ms and 30 ms and between 230 and 380 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

The delta2-opioid receptor subtype stimulates phosphoinositide metabolism in mouse periaqueductal gray matter.

The delta(delta)-opioid agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II increased the formation of inositol phosphates (IPs) in mice periaqueductal gray matter (PAG) slices pre-labeled with myo-[3H]inositol. Both delta-agonists caused an increase in IP accumulation in a dose-dependent manner (1-100 microM) and which was pertussis toxin (0.5 microg/mouse, i.c.v.) sensitive. This effect was blocked by the delta-antagonist ICI-174.864 (10 microM). The presence of subtypes of the delta-opioid receptor (delta1 and delta2) in PAG has been suggested by pharmacological studies. In this brain structure, naltrindrole 5'-isothiocyanate (5'-NTII), but not 7-benzylidenenaltrexone (BNTX), antagonized the effects of DPDPE and [D-Ala2]deltorphin II, suggesting the involvement of a population of delta receptors sensitive to the delta2-antagonist NT II on this effect. To further investigate the participation of delta-receptor subtypes in the stimulation of IPs formation, mice were injected with antisense oligodeoxynucleotides (ODNs) directed to nucleotides 7-26 or 2946 of the cloned delta-receptor mRNA, and PAG slices from these animals were used in in vitro assays. The results demonstrate that the reported increase of phosphoinositide (PI) hydrolysis depends on the agonist activation of the delta2-opioid receptor subtype in the PAG.

[Laparoscopic treatment of severe acute pancreatitis. A case report]. / Tratamiento laparoscópico de pancreatitis aguda grave. Reporte de un caso.

OBJECTIVE: To report the laparoscopic treatment of a patient with severe pancreatitis. BACKGROUND: The efficiency and advantages of laparoscopic surgery in the management on acute abdominal diseases has been demonstrated. The laparoscopic approach has been reported in the diagnosis and treatment of several pancreatic diseases, including severe cases of pancreatitis and its complications. MATERIALS AND METHODS: A 70-years-old male patient with acute abdomen in which a diagnostic laparoscopy was performed finding acute cholecystitis and severe pancreatitis. Seven days later because a torpid course required a reintervention to perform laparoscopic necrosectomy. CONCLUSION: The laparoscopic treatment in severe pancreatitis is possible in selected cases and offers advantages over the traditional procedure. Prospective studies and protocols are necessary to validate the laparoscopic approach in the diagnosis and treatment of severe pancreatitis.

Effect of salinity on enzymatic activities in a submerged fixed bed biofilm reactor for municipal sewage treatment.

The effect of salinity on the hydrolytic enzymatic activities (acid phosphatase, alkaline phosphatase, glucosidase, protease and esterase) released by the microorganisms in a submerged fixed bed bioreactor for real urban wastewater treatment was investigated. The influence of salt (NaCl) on the enzymatic activities was evaluated in four different experiments with concentrations of NaCl of 0, 3.7, 24.1 and 44.1g/L, remaining constant all other operating parameters of the bioreactor. The results show that enzymatic activities were reduced when the salinity was increased in the influent and consequently the biotransformation of organic matter in the submerged fixed bed bioreactor significantly decreased. A redundancy analysis was performed to evaluate the relationships between enzymatic activities and physic-chemical parameters analyzed in the influent. According to the results obtained with the Monte Carlo permutation test, salinity and sampling day significantly contributed to explain the variation of enzymatic activities, showing a negative correlation.

[Non invasive gene therapy in neurological diseases]. / Terapia genica no invasiva en enfermedades neurologicas.

INTRODUCTION: Brain gene therapy consists of introducing nucleic acids into nerve tissue whose expression may prove to be therapeutically useful. This genetic material is indirectly introduced by means of non invasive gene therapy into the blood thereby avoiding its direct injection into the brain and the damage to the blood brain barrier. AIM: The different non invasive vectors and means of gene transfer to the central nervous system will be discussed. DEVELOPMENT: There has been a remarkable breakthrough in recent years in non invasive gene transfer strategies into the central nervous system. The development of new serotypes of adenoassociated vectors, such as AAV9, and of functionalized nanoparticles, such as pegylated immunoliposomes, polymeric nanoparticles, pegylated nanoparticles, dendrimers, fullerens, as well as specific transporters specific to the low density lipoprotein receptor family, means that it is now possible to introduce and express gene material in nerve tissue following peripherical administration of the above mentioned vectors. CONCLUSIONS: Non invasive gene therapy entails exciting new perspectives for the treatment of the numerous neurological diseases for which there are no effective pharmacological treatments. Studies already performed on animals have proved to be highly promising and it is likely that, in the next few years, they will give rise to non invasive gene therapy procedures which will be useful and safe for treating patients.

What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

We have studied motor performance in a man with Parkinson's disease (PD) in whom thermolytic lesions of the left subthalamic and left globus pallidus nuclei interrupted the basal ganglia (BG)-thalamo-cortical motor circuit in the left hemisphere. This allowed us to study remaining motor capabilities in the absence of aberrant BG activity typical of PD. Movements of the left arm were slow and parkinsonian whereas movement speed and simple reaction times (RT) of the right (operated) arm were within the normal range with no obvious deficits in a range of daily life activities. Two main abnormalities were found with the right hand. (a) Implicit sequence learning in a probabilistic serial reaction time task was absent. (b) In a go/no-go task when the percent of no-go trials increased, the RT superiority with the right hand was lost. These deficits are best explained by a failure of the cortex, deprived of BG input, to facilitate responses in a probabilistic context. Our findings confirm the idea that it is better to stop BG activity than allowing faulty activity to disrupt the motor system but dispute earlier claims that interrupting BG output in PD goes without an apparent deficit. From a practical viewpoint, our observations indicate that the risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producing deficits that impair activities of daily life.

Displasia evolutiva de cadera: controversia sobre el cribado ecográfico universal / Developmental hip dysplasia: controversy on universal echographic screening

Pese a la elevada incidencia de displasia de cadera clínicamente importante (3-5 casos por cada 1000 recién nacidos vivos) y a los ampliamente estudiados factores de riesgo principales (parto de presentación podálica, sexo femenino y antecedentes familiares de displasia evolutiva de cadera), no se ha conseguido encontrar una estrategia efectiva que reduzca la incidencia de casos tardíos. Reabrimos, a propósito de un caso, la controversia existente acerca del cribado ecográfico universal en la patología osteomuscular más frecuente de la infancia (AU)

Despite the elevated incidence of clinically relevant hip dysplasia (3-5 per 1000 live births) and the broadly studied main risk factors (breech position, female sex and family cases), we have not achieved an effective prevention strategy, and so the detection of late cases has not decreased. We reopen, following a case, the existent controversy upon universal ultrasound screening on the most frequent musculo-skeletal disorder in the infancy (AU)

Antisense oligodeoxynucleotide targeting distinct exons of the cloned mu-opioid receptor distinguish between endomorphin-1 and morphine supraspinal antinociception in mice.

Antisense oligodeoxynucleotides (ODN) were used to investigate the supraspinal antinociceptive effects of endomorphin-1, an endogenous peptide whose analgesic profile suggests that it is a ligand at the mu-opioid receptor. To selectively restrict the expression of this receptor, five ODN targeting distinct exons of the gene sequence were injected subchronically by the intracerebroventricular route (i.c.v.) into mice. The antinociception induced by endomorphin-1 was greatly reduced in animals receiving the ODN directed to nucleotides 677-697, which code for a sequence located on the second extracellular loop of the mu receptor. ODN-mu(un), one of the two antisense ODN directed to exon 1, also impaired endomorphin-1 antinociception. ODN targeting exons 2 and 4 were totally inactive. In contrast, all five ODN blocked the antinociception induced by morphine and beta-casomorphin. The analgesic potency of endomorphin-1, morphine, and beta-casomorphin remained unaltered by administration of an ODN to nucleotides 29-46 of the murine delta-opioid receptor gene sequence of a random-sequence ODN. This suggest the existence of diverse molecular forms for the mu-opioid receptor that mediate the antinociceptive effects of endomorphin-1 and morphine/beta-casomorphin.